The Simple Plant Isoquinolines

Definitions:

Consider botany. What is a taxon? It is the name which identifiesa plant. A taxon is made of two parts. First, there is the genus,which is a general name given to a group of closely related plants.Second, there is the species, which is the distinguishing namegiven to a specific plant in that group. A taxon is always writtenin italics. Thus, for example, Pachycereus pecten-aboriginum is thename of a cactus.

Consider chemistry. What are isoquinolines? These are chemicalstructures built around a two-ring compound. This compound,Isoquinoline, consists of a benzene ring and pyridine ring fusedtogether at a specific bond. There is a pattern of substitution thatgives an isoquinoline its absolute definition. Thus, for example,Salsoline is an isoquinoline, which is a major component of thePachycereus pecten-aboriginum plant.

One can identify a plant by what it looks like, or by what is in it.One can identify a natural compound by its structure, or by whatplant it is in. Know one, find the other. This reference book hasbeen designed to make this cross-identification easier to achieve.

TABLE OF CONTENTS

Foreword I vi

Foreword II xi

Introduction xiii

TrivialName Index 1

Structural IndexUnsubstitutedMonosubstitutedDisubstituted

5,6- 5,7- and 5,8-substituted6,7 -HO,HO-substituted6,7-HO,MeO-substituted6,7-MeO,HO-substituted6,7-MeO,MeO-substituted6,7-MDO-substituted6,8-substituted7,8-substituted

Trisubstituted5,6,7-substituted5,6,8-substituted6,7,8-substituted

Tetrasubstituted

3941

46475288

161245347349

372425426455

Taxon Index 458

Plant Families Appendix 602

Isobenzofuranone Appendix 610

Journal Names Appendix 616

v

vi

FOREWORDI

The passion of my life over the last forty years has been a compellinginterest in psychedelic drugs. They have given me not only an excitingarea of research and discovery, but also a personal understanding of justwho I am and why I am. Certainly these guides and sacraments willeventually play an accepted role in our community and in our culture.Almost all of these drugs have either been isolated from psychoactiveplants, or are the results of subtle variations of the molecular structures ofthese isolates.

I have always looked at these plants and the compounds they containin the same way that the Romans dreamt of their ultimate empire. It wasCaesar who acknowledged that all of Gaul was divided into three partsand to understand it, to conquer it, each part had to be respected as aseparate entity. It is exactly the same way with understanding the worldof psychedelic drugs. There are three domains of inquiry that must bestudied independently before one can begin to appreciate just how theymight integrate into a single concept. These three are now, I believe,coming together.

One part is the large collection of psychoactive compounds known asthe phenethylamines. The first known plant psychedelic was mescaline,or 3,4,5-trimethoxyphenethylamine. This simple one-ring alkaloid wasdiscovered in the North American dumpling cactus Peyote (Anhaloniumtoilliamsii) in the late nineteenth century, and is now known to be a com-ponent of over fifty other cacti. Over a dozen other cactus phenethyl-amines have been isolated and identified, and there are perhaps a hun-dred synthetic analogues that are now also known to be psychedelic inaction. This body of information has been published by my wife Ann andme as a book entitled "PIHKAL:AChemical Love Story." PIHKAL standsfor Phenethylamines I Have Known and Loved.

An almost-as-large chemical group contains the tryptamines. N,N-Dimethyltryptamine (DMT), its 5-hydroxy analogue (bufotenine) andthe O-methyl ether homologue 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) are widely distributed in the world of natural plants. Thereare also the well-established mushroom alkaloids 4-phosphoryloxy-N,N-

vii

dimethyltryptamine (psilocybin, and the dephosphorylated indolol psilo-cin)and the mono- and didemethylated homologues baeocysteine andnorbaeocysteine. These seven natural alkaloids have provided the tem-platefor perhaps two dozen analogue structures that are now well-estab-lishedpsychedelic agents. Ann and I have written a companion volumeto PIHKAL called "TIHKAL: The Continuation" (TIHKAL stands forTryptaminesI have Known and Loved), which has brought together mostofthese natural and synthetic tryptamines into a single reference site.

The remaining third of the above Gallic synthesis deals with what Ihad originally called the "Q" compounds, as distinguished from the "P"compounds and the "T" compounds (the phenethylamines and thetryptamines). The actual parent structural element is the isoquinoline ringsystem,and my initial plan was to give this third book a name similar tothe first two. IIHKAL wouldn't do it, but QIHKAL shows a good bit ofclass, at least in my opinion. Or maybe THIQIHKAL because most ofthem are really tetrahydroisoquinolines. Well, all these names are nowon hold, as Ann is uncomfortable with them. No name has yet beendecided upon, but ideas such as The Third Book, or Book Three, areunder consideration. Names like these resound with a rather strikingarrogance, if nothing else.

Tounderstand the relationship of the isoquinolines to the phenethyl-amines and the tryptamines, the concept of ring closure must be used.Thisisa sort ofsynthetic scorpion sting at the molecular level. A tryptaminehas an indole ring as its centerpiece and from it there extends a floppytwo-carbon chain terminated by an amino nitrogen atom. A small butvery important family of plant alkaloids is the product of this amine ex-ploitinga carbon atom from somewhere, and making a new six-memberedringby that "sting" reaction back onto the parent indole ring. This familyhasthe name,~-carbolines, and the formed compound is 1,2,3,4-tetrahydro-[3-carboline.

QCNHNIH

tryptamine 1,2,3,4-tetrahydro-~-carboline

Aphenethylamine has a benzene ring as its centerpiece and it, too, hasa floppy two-carbon chain extending out from it and also terminating inan amino group. In a reaction that is exactly analogous to that of thetryptamines, this amine can pick up a carbon atom and bend back to react

viii

with the parent benzene ring forming a six-member ring. This is the ori-gin of the isoquinoline family of natural products, and the formed com-pound is l,2,3,4-tetrahydroisoquinoline.

phenethylamine 1,2,3,4-tetrahydroisoquinoline

As mentioned above, this third part of the plant psychedelic alkaloidworld involves tetrahydroisoquinolines and is the substance of our thirdbook. A very reasonable appendix to be written for this book would be asearch of the chemical literature for the known isoquinolines that mightbe of interest as pharmacological agents. There are certainly many plantproducts, as well as a monster inventory of synthetics, some of which aremade based on plant examples, but many others are simply laboratorycreations of the imaginative chemist.

It was soon apparent that this compilation would become unmanage-ably large. The first major trimming was the elimination of the compoundsthat were synthetic, and the limitation of the listing to those compoundsthat have been reported as plant products. These isoquinolines could playthe dual role of serving not only as potential contributors to the action ofpsychoactive plants but also as prototypes for the synthesis of newmaterials that might themselves be biologically active.

But even this restriction to only plant compounds was not sufficientlysevere. There seemed to be no end to existing isoquinoline treasures. AsI wandered deeper into the literature, I kept finding an ever-increasinginventory of research papers that described fantastic stuff. As a totallymake-believe example, pretend that there was a compound namedDogabinine that has only been found in the Dogabic tree in the Twathturainforest, which the natives say cures leprosy, and which has a complexchemical structure that just happens to carry an isoquinoline ring in itslower southwest corner. To include all such monsters would make theappendix many thousands or even tens of thousands of pages long. Andif you were to add into this compilation all the known derivatives, exten-sions and chemical modifications of Dogabinine, then you would have areview entity that would be several volumes in length. If such a collectionwere to exist, I would have it in my library right now. But it does not existand it may never exist.

IX

Somemiddle ground, some rational compromise, had to be found. Iwanted this collection to present all isoquinolines that are known to beplantalkaloids, but respecting carefully defined restrictions that excludehorrormonsters such as Dogabinine. The final compromise was to estab-lishseparate entries for all the known two-ring isoquinolines that are fromnatural sources, including those that carry a third ring as a substituent(suchas a benzyl group) at the I-position. And within each of these en-tries,there are included all natural alkaloids that can be seen as productsofa hypothetical attack of an ortho hydrogen of this substituent on someotherposition of the isoquinoline nucleus. This "ortho-X attack" is ex-actlydefined and illustra ted in the Foreword tha t follows. All plant sourcesare recorded (or representative sources if there are too many) and litera-turecitations are also included in each entry.

But even with these restrictions, this "appendix" to a third book wasbecominglarger and larger, and it soon became apparent that it was to-tallyinappropriate. There would be far too many pages for a minor ap-pendixin a book that is to be dedicated to cactus and isoquinolines. Andby the time my stream-of-consciousness commentary was added in thetextwhere I felt it should be added, the mass increased to the extent that ithad to be a reference book in its own right.Voila. Let's try to get all that information together into a single modest

packageand make it available to the chemists and botanists who mightwant it. Should it be a review article in Chemical Reviews or the Journalof Natural Products? Several factors said "No." Most botanical reviewsurveysare not searchable except by taxon name (that would assume thatyouwould know the plant from which it came) or by some complex andmaddening Chemical Abstracts entry that dealt with some alphabetiza-tionthat demanded the knowledge of the structure and the way the struc-turewould be listed. And most review articles also insist on a tidy forma tthat iswithout editorial comment and does not contain volunteered ideasand extrapolations.Anobvious solution became apparent. Create a single reference book

to contain all this information. Use the chemical substituents as analphabet. Visually travel around the structural image of the molecule in alogicaldirection, address the substituent groups in some logical way whichwillbe called alphabetical, and progress until you find the target you aresearchingfor, or until you find an empty hole where it would have beenhad it been known. So this book has come into existence simply to meetthis need, and to relieve the potential "Third Book" readership of a killerofan appendix.

Thenature of the substituents and, especially, the connection betweensimplebenzylated isoquinolines and the nature of the cyclized productsofortho attacks, are the heart and substance of this review book.

xOne additional comment is essential in this introduction. The exten-sive literature searching, and commingling of the accumulated plant andchemical data, taxed my capability and exceeded my patience. This wasindeed a compilation that was essential to my current cactus research forthe third book, but the task of its organization created a disruptive inter-ference to my exploration of new psychedelics in unanalyzed cacti. Theearly help given me by Ann's daughter Wendy quickly evolved into herplaying an indispensable role as my co-author. The final organizationand structuring of this book has been largely the result of her dedicatedlabor. It is an honor to share the authorship with her as, without her help,this book would not exist today.

Alexander T.Shulgin

Xl

FOREWORD II

When Sasha and I began this project it was meant to be an appendixforthe next book in the series of PIHKAL and TIHKAL. It became so bigthatwe knew after some time it could not be an appendix; it was its ownbook. Sohere it is, a collection of all the information we've compiled overthelast two years. It's been a daunting project at times. If we had includedall the variations of isoquinolines that we had originally planned to, thisbookwould have been a series of volumes. Along the way we had tomakedecisions about what was important to keep in, what we could leaveout,what our focus was, what our intentions were. We pared down con-stantly,finally settling on the criteria that Sasha has laid down in the in-troduction.

It ismy belief that what we have put together here will be of great useto anyone interested in this particular field of botany and chemistry. Wehavetried to make the information as easy to find and review as possible,taking into consideration what it was like for us to search through theliterature.Hopefully this compilation will make others' work much easier.Wefound so many mistakes in the literature, and even in the ChemicalAbstracts, that we had to make educated guesses as to the correct waysomethingwas spelled, or what a certain substituent was on a given ring;sometimeswe simply made comments in the text about a particular dis-crepancy.Wewelcome corrections and comments that come to us, as wesurelyhave made errors ourselves.

What I observed while going through the literature was enlightening.What stood out for me was how much of the plant research done onisoquinolineshas been in countries other than the United States. As manypeopleknow, the state of objective, independent scientific research in thiscountryis a sad one. Research is at the mercy of special interests, govern-ment funding, and of harsh regulations and restrictions. It's rare to havea situation where a scientist is free to explore and discover, much less en-couragedto do so. We are left to rely on research done in countries wherethe scientists' findings are not bought and paid for in advance, as hap-pens in this country too often. Sasha is a rare chemist indeed, workingindependently for so long, free of those controls, and following his pas-sionto discover tools to understand the mind and the brain in the face of

xii

much misunderstanding and misguided assumptions about psychoactivematerials. As it is now, the pharmaceutical industry is bridging the gapbetween what is socially and legally acceptable to do to one's brain chem-istry in order to feel well, and what is currently considered unacceptable,which is using chemical or plant medicines to look at why one is not feel-ing well to begin with.

There is great hypocrisy, fear, and thoughtlessness afoot in the UnitedStates regarding psychoactive drugs. Their benefits and potential uses arelost in the rhetoric of the "drug war," and in the fear that it generates.There are many examples of healthy and informed use of psychoactivemedicines throughout the world, and throughout the ages. They havebeen used in the past, and are being used today, as healing tools. Weneedthat kind of thinking in this country, we need that kind of healing.

Hypocrisy exists in the laws regarding alcohol and tobacco, which arelegal, and are the most damaging and widely abused drugs in our culture.Many pharmaceutical drugs are not without their dangers and abuses aswell (it's a fact that far more Americans die from pharmaceutical drugsthan illegal drugs). What are the fears of psychoactive drugs really basedon? I encourage those who start with the arguments of brain damagecaused by this or that drug to obtain the actual scientific papers that makethose claims (not just the titles of the papers) and read them carefully.They will find much misinformation due to political pressure, economics,and fear.

It's been a blessing to work with Sasha, who is not only a brilliantchemist but a fantastic teacher. I had no background in chemistry when Ibegan working with him; he has taught me so much. His passion andenthusiasm for chemistry is infectious; he has made it a delight to learn,and has shown me how magical it all is. It is magical, and mysterious, thisworld we live in and the stuff that it and we are made up of. It should becherished, protected, and explored, with honesty and courage.

Wendy E. Perry

Introduction xiii

INTRODUCTION

Forthis book to serve as a completely satisfactory reference, it mustbestructured so that a reader who comes to it with one specific wordinmind that is related to the simple, natural isoquinolines, can imme-diatelylocate all other related entries. Total cross-referencing is needed.Asa way to simplify this type of search, the main part of this book isactuallya collection of three indices. Each index is arranged alphabeti-cally,very much like a dictionary. The first index lists the commontrivialnames, the second lists the structures of the compounds them-selvesand the plants that contain them, and the third lists the taxo-nomicnames of these plants and the compounds that have been foundin them.

Part 1: Trivial names of the plant alkaloids:

Allof the known simple plant isoquinolines have been entered intothisindex under their common, or trivial names. Originally, there wasalinearstructure code attached to the trivial name entry which allowedthereader to immediately deduce the chemical structure and to accessthecompound directly in the structural index. It became apparent thata singlepage reference would do as well. Each trivial name thus leadsto the chemical structure, the plants that contain that compound, andappropriate literature references.

Many compounds have a number of trivial names. These may bepuresynonyms for a single compound, or they may distinguish differ-ent structural or optical isomers. The quaternary amine alkaloid saltspresentan unusual problem. There are three naming procedures thatare frequently encountered. The quaternary salt may have a distinctone-wordname. Here there is no problem. However, the other twoexamplesare two- or three-word names, with the anion involved be-ing incorporated into the second word. As the fourth alkyl group onthenitrogen is usually a methyl group, the anion name would take oneof two forms. If the parent tertiary amine is, say, the alkaloid Cana-dine, then the methyl quaternary salt could be called either N-Methylcanadinium iodide or Canadine methiodide. Both are faultedin that the presence of the iodide anion in the product is the work of

xiv The Simple Plant Isoquinolines

the analyst, and it is not what was originally present in the plant. Andif five people were to independently isolate this plant product and char-acterize it as a salt using the anions chloride, iodide, picrate, perchlor-ate and oxalate (all commonly found in botanical papers) it would de-mand five different index entries for a single plant alkaloid. In thispresent compilation, N-Methylcanadine quat will be the name used.But some quaternary amines are internally tetra-substituted. With com-pounds such as the berberines where the c-ring is aromatic, there is noexternal "methyl" group to call upon. Here, using Caseadinium io-dide as an example, the anion will also be dropped and it will be listedas Caseadinium quat.

Part 2: Structural formulae of the plant alkaloids:

The second, and major, index is the collection of structures and theirplant sources. This section is also organized in an alphabetical way,but clearly the use of the classical A to Z order does not apply to thevarious arrangements of atoms. Let's say you have the structure of asimple isoquinoline in mind, and you would like to know if it is a knownplant alkaloid. The classic academic process is to head over to the Uni-versity library and start going through the many collected indices ofthe Chemical Abstracts, and search it out by what you hope is the rightchemical name. But sadly the rules of naming are continuously chang-ing. Sometimes 5,6,7,8-tetramethoxy precedes l,2,3,4-tetrahydro, andsometimes it follows it. Sometimes 6,7-methylenedioxy-l,2,3,4-tetrahydroisoquinoline is filed in just that way, but sometimes it is filedunder benzodioxolol4,5-gJ5,6,7,8-tetrahydroisoquinoline. And justwhat are the Chemical Abstracts' structural naming rules and number-ing systems for four-ring systems such as aporphines, isopavines orberberines?

The "alphabet" used in this structural index is totally indifferent tothe capricious and arbitrary rules laid down by the Chemical Abstracts.Quite simply, it is based on the location of the substituents and theiridentity in the nuclear isoquinoline skeleton before it is distorted by ahypothetical "ortho attack." The definition of this "atomic" alphabetis the substance of this introduction. The nature and variety of this"ortho attack" is addressed here as well.

Part 3: Botanical names for the plants that contain these alkaloids:

All plants have been entered into the third index alphabetically,according to genus and species. Under each of these taxa are listed thetrivial (or chemical) names of the alkaloids reported to be in that plant.

Introduction xv

Part 4: Appendices:

There are three appendices located at the end of this volume. Thefirstis a listing of the botanical families that are mentioned in this book,and the Genera that each contains. Second is an analysis of the non-intuitive process used by Chemical Abstracts to create the name of anisofuranone-substituted isoquinoline. The third is the list of actual jour-nal names that are given only as initials in the references in the struc-tural index.

THEATOMICALPHABETIZATION OF COMPOUNDS

There are two "alphabets" used in the organization of this book.Boththe index of trivial names and the listing of the botanical binomi-als use the English A to Z, 26-letter convention, like a dictionary, andthewords can be of any length. The listing of compounds in the struc-tural index is also "alphabetical," but it employs a hierarchy of posi-tionallocations and structural substituents as its alphabet. Each struc-ture is a five-lettered "word" and the priority follows the rules of thedictionary. With the structure being sought in mind, one must gothrough the list of compounds with the first "letter" (substituent) inmind, and then the second "letter" is located, and on, and on. Below isa list of the priorities each substituent ("letter") follows.

(l) POSITION ON THE AROMATIC RING

Here is the primary assignment of numbered positions, and theassignment of letters to the individual bonds, of the isoquinoline ring:

5 4a 4600~37 ~ I ~N2

8 8a 1OJ

fed C-:/'" I ~9 b~ ~Nh i j a

The first "letter" of the chemical name of the structure being soughtis created from the position of the substituents on the aromatic ben-zene ring. There are four positions available (5,6,7,8), and they are al-phabetically arranged from small to large and from few to many.

xvi The Simple Plant Isoquinolines

This is the order:

none 5 5,6 5,6,7 5,6,7,86 5,7 5,6,87 5,8 5,7,88 6,7 6,7,8

6,87,8

Thus a compound with a 5,6-disubstitution pattern is to be foundin this dictionary immediately following the 8-monosubstituted entriesand immediately before the 5,7-disubstituted entries. All numberinghas been taken exclusively from the assignments given to theisoquinoline ring. There are situations such as the methylenedioxy-isoquinolines where the nature of the substituent constitutes a new ring.In this case, as in many others, Chemical Abstracts would assign to-tally different numbers to these four positions on the aromatic ring.Currently correct numbering systems are ignored here, and the primi-tive 5,6,7 and 8 positional identifiers are used exclusively. This firstletter of the structural alphabet is used as a heading for the appropri-ate subsection of the second index, the structural formula group.

(2) THE SUBSTITUENTSON THE AROMATIC RING

The second "letter" of the chemical name is the actual substituentor substituents found at the positions designated by the numbers above.There are only three substituents to be considered in this chemical al-phabetical sequence; they are, in order:

code atomic commonused: connections: name:

HO HO- (hydroxy)MeO CH30- (methoxy)MOO -OCH20- (methylenedioxy)

The HO- group is exactly what it appears to be. It is a hydrogenatom bonded to an oxygen atom which is, in turn, bonded (at least inthe case of the second letter of this chemical alphabet) to one or moreof the available positions on the aromatic ring of the isoquinoline, i.e.,the 5,6,7 and/or the 8 positions. The MeO- group, as drawn, is an ab-

Introduction XVll

breviationfor a slightly more complex structure, a methyl group (H3C-or-CH3)bonded to an oxygen atom which is, as above, attached to one(or more) of the four positions of this aromatic ring. The MOO, ormethylenedioxy group, is yet a bit more complex. It is unique in that itis a double-ended substituent. It is a short chain that involves an oxy-genatom (0) connected to a methylene group (CH2) connected in turnto another oxygen atom. Drawn out as a collection of atoms it is-OCH20-and thus requires two adjacent substituent positions and mustbe associated with two numbers.

Let's use the 5,6 substitution position as an illustration template,andwe'll introduce some substitution second "letter" examples, in al-phabeticalorder:

5,6 HO HO5,6 HOMeO5,6 MeOHO5,6 MeOMeO5,6 MOO

precedesprecedesprecedesprecedes

A few things are obvious. Where a thing is located (shown by thenumberor numbers) has priority over what a thing is (the substituentor substituents). This same locating and identifying code will be usedfor the benzyl group on the I-position, but with some extensionswhich will be explained below.

There is, of course, a fourth allowable substituent. This is H (ahydrogen atom), but it is automatically assumed to be on every num-beredposition not carrying one of the three given oxygenated examples.It is generally accepted, in the creation of a name to represent a chemi-cal structure, that if there is no substituent specified on the aromaticring the substituent is hydrogen, and is not entered. The presentationof the entry

5,6 MeO HO - without this exclusion, would have been5,6,7,8 MeO HO H H

What about substituents that are groups other than HO, MeO orMDO(and of course the unsubstituted H)? Homologues of Mea suchasethoxyand benzyloxy (Eta, BzO), alkyl groups such as methyl, phe-nyl,halides, carboxy or substituted carboxy groups, esters of phenols,

xviii The Simple Plant Isoquinolines

nitrogen-containing groups such as nitro or amino derivatives, thiocompounds, all are regularly encountered as substituents ofisoquinolines in the chemical literature. And since almost all of themare products of synthesis rather than plant products, they are ignoredin this compilation. There is an occasional exception, like an O-acetylderivative that appears to have been isolated from some natural source.

There are plant alkaloids known that can, within the plants' envi-ronment, undergo extensive oxidation. In the aporphine group, a com-pound such as Norcorydine can go to the quinone, all four rings com-pletely aromatic and a carbonyl at the 7-position where the hydroxygroup once was. This is the base Pancoridine. So a quinonic carbonylcan appear in the aromatic ring. But its origin was a hydroxy group.So, for all practical purposes, we are staying with the three substitu-ents mentioned above (other than hydrogen). The substituents that areon the benzene ring are listed on the first line in the box at the upperleft corner of each compound's entry, in the sequence that correspondsto the number or numbers at the top of the page.

6-MeO 7-HO3,4-MeO,MeO-benzylH IQ

(3) THE I-POSITION

The third "letter" of this alphabet is the substituent that is found atthe I-position of the isoquinoline ring. This is the first involvement ofthe pyridine ring position of the isoquinoline system, so a number ofnew factors must be considered. There are always two substituents atthis position but, depending on the degree of aromaticity of this ring,one of them might be meaningless. And, as there are two substituents,there must be a rule that ranks them. If they are different, the heavierwill precede the lighter. This lighter one will be a hydrogen or a me-thyl group (abbreviated Me). And occasionally there will be a sub-stituent that embraces both substituents as a single thing. And again,as above, there will be occasions where the unnamed substituent issimply hydrogen, and is not mentioned.

Here is the sequence that will be used, listed by what the substitu-ents really are, and by how they will be entered.

Introduction xix

Heavier substituentat the I-position:

Lighter substituentat the [-position:

Appearance of thisthird chemical letter:

HMeMeOHOHRRR

HHMeHMeHMeHO

HMeMe,MeOH or (=0)OH,MeRR,MeR,HO

In those cases where there are two different substituents, this car-bon atom becomes chiral. Most natural products have optical activity,but in many plant analyses, the optical rotation is not reported andprobably not measured. In the literature there is no way to distinguishbetween an unknown rotation and a racemate. In these cases, all plantsources for a given isoquinoline have been commingled without re-gard to the reported optical activity, unless it is known.

The "R" that is mentioned above is one of five aromatic systems,and these are usually substituted themselves. These aromatic systemsand their numbering are ranked as shown below:

.c.' ~6cr5 ~ 3 4 ~ 2 6 2

4 3 5 3R= phenyl R= benzyl

R= ~-phenethyl

5 5~I 0 I 06 ~ 6 ~

7 OH 7 0

R= isobenzofuranol, 3'-yl R= isobenzofuranone, 3'-yl

The priorities for both the numbering and the substituents followthe same patterns established for the first and second chemical letters.

xx The Simple Plant Isoquinolines

Numbering priority:

none 2 2,3 2,3,4 2,3,4,5 2,3,4,5,63 2,4 2,3,5 2,3,4,64 2,5 2,3,6 2,3,5,6

2,6 2,4,53,4 2,4,63,5 3,4,5

And once the numbers have been decided upon, then the substitu-ent is chosen from the following sequence:

HOMeOMOO

Again, there are many known compounds that have phenyl, ben-zyl or phenethyl rings at the 'l-position with substitutions other thanthese three (and the understood and unstated hydrogen atom of course).And, as with the 5,6,7,8 substitution story, most of these are syntheticproducts and are not part of this book. The few unusual substitutionsthat are known to be in compounds from natural sources, such as theformyl (CHO) and the carboxyl group (C02H), will be included. Therule of organization is: a group bonded with a carbon atom has prior-ity over a group bonded with an oxygen atom.

Occasionally there is a carbon or an oxygen substituent found onthe alpha-carbon atom of the benzyl group. This is taken into accountin the alphabetization. These substituents have the following priority:

Mono-substituted Oi-substituted

Me (methyl)HO (hydroxy)AcO (acetoxy)MeO (methoxy)NH2 (amino)

Me,Me (dimethyl)Me,HO (methyl, hydroxy)= CH2 (rnethenyl)= 0 (oxo) or (keto)

The presence of a carbonyl at the 'l-position introduces an ambigu-ity. In most cases, the structure of the I-keto product can be redrawnas a I-hydroxy tautomer with the inclusion of a double bond in thepiperidine ring to balance the equation. When this situation occurs,the compound will be entered as the keto tautomer.

Introduction XXI

OQOH

O)Ha

This third letter of the atomic alphabet, the 'l-position, is entered onthe second line in the box found at the upper left corner of each entry.

-~.-6-MeO 7-HO3,4-MeO,MeO-benzylH IQ

(4) THE 2-POSITION

The fourth "letter" in this chemical alphabet is the substituent atthe 2-position, the nitrogen atom, of the isoquinoline ring. The pri-mary substituents found here are the hydrogen and methyl groups,and they are arranged by increasing number:

HMeMe (+)Me,Me(+)CHOC02HAc (COCH3)CONH2C02MeC02Et

(formyl)(carboxy)(acetyl)(carbamoyl, or urea)(carbomethoxy)(carboethoxy)

An "H" as the fourth letter does not necessarily mean that there is ahydrogenat this position. It is an indicator of the absence of any substitu-tionon the nitrogen. This, as with the absence or presence of a (+) chargeat that position in the methylated examples, reflects the aromaticity of thepyridine ring. This is discussed below in section (5). There are also found,occasionally,amide functions on this nitrogen atom.

Oxidation at this position is frequently found. Hydroxylaminesand N-oxides are entered either as footnotes to their non-oxygenated

XXll The Simple Plant Isoquinolines

counterparts or as entries in their own right. There are about a dozenplant isoquinolines that have benzyl substituents on the nitrogen atom.They are included in this collection.

This fourth letter of the atomic alphabet is found at the left side ofthe third line in the box at the upper left corner of each entry.


t(5) HYDROGENATION

The fifth letter of the chemical alphabet is the simple statement ofthe degree of hydrogenation of the pyridine ring, and the three codesare ranked in the order of increased aromaticity,

THIQDHIQIQ

tetrah ydroisoq uinolinedihydroisoquinolineisoquinoline

THIQ is l,2,3,4-tetrahydroisoquinoline. Both double bonds in thepyridine ring are hydrogenated. If the fourth letter is an "H," there isindeed a hydrogen on the nitrogen. If there are methyl groups there, asingle methyl will be without a charge, but two methyls will require a(+) charge.

DHIQ is specifically 3,4-dihydroisoquinoline. If the fourth letter isan "H," there is no substitution on the nitrogen, even though there willbe an H written on the third line on the left side. If there is a methylgroup indicated, there must be a (+) associated with it. There is anoccasional natural dihydroisoquinoline in which the hydrogenation isat the l,2-positions and the unsaturation is at the 3,4-positions. Thesehave been entered as a footnote under the THIQ compound as 3,4-ene.

Introduction XX111

IQis the completely aromatic compound. Again, in this case, if the4thletter is indicated as an H, there is no substituent on that nitrogenpositionand if there is a methyl there, it must have a (+) on it.

This last letter is noted as a THIQ, DHIQ or IQ on the right-handside of the third line in the box at the upper-left corner of thecompound's entry.


tTHEoRTHo ATTACK

Oneof the little appreciated but totally fascinating properties sharedby perhaps a dozen of the classes of four-ring isoquinolines is that mostofthemcan be visualized as resulting from an 11ortho attack," from the2- or 6-hydrogen atom of the I-substituent (usually a benzyl group) tosomespecifically identified position of the isoquinoline ring. Theseconversionsmay certainly have biosynthetic reality. But they have agreatdeal more importance for this book in that they allow a simpleandfoolproof way of organizing the compounds in text. To locate thetargetcompound under which the four-ring material will be found,simplymentally note the I-benzylisoquinoline that constitutes itschemicalskeleton. The bond forming the fourth ring can be identifiedasgoingfrom an ortho-position of the benzyl to some numbered atomonthe isoquinoline. Below they are illustrated and identified as to thealkaloidalclass name. One must keep in mind that the benzyl ring hastwoortho hydrogens. If it is not symmetrically substituted, the nor-malnumbering priority sequence is used, and that will dictate whethertheorthohydrogen employed in the attack is a 2- or a 6-hydrogen. Theexamplesbelow show ortho (2,X)attacks. It should be understood thatthesubstitution pattern on the benzyl ring could require that they becalledortho (6,X) attacks. The ortho attacks will be indicated in eachsectionin a separate box from the first. Thus, the first box in eachsectionis the parent compound, and any additional boxes will be modi-fications,such as an ortho attack, an N-oxide, or other changes.

xxiv The Simple Plant Isoquinolines

Spirobenzylisoquinolines

The ortho (2, 1-Me) attack

This family is classified in this collection as an ortho-attack on al,l-disubstituted tetrahydroisoquinoline where there is a methyl, orsome other group (an ortho (2,1-XX)attack).

Dibenzopyrrocolines

The ortho (2,N) attack

Here the hypothetical2,N (or 2,2) attack produces a five-memberedring. The tetracyclic product is treated here as an isoquinoline, but itcan also be seen as a disubstituted dihydroindole. The usual chemicalclassification is that of a substituted pyrrocoline, the name for the het-erocycle that is the middle two rings of this system.

Introduction xxv

Protoberberines (Berberines) and Protopines

The ortho (2,N-Me) attack

with ring C aromatic

The N-methyl oxo and oxy forms

Thisis one of the more common ortho attacks, and gives rise to theprotoberberines and, with a minor substitution change, the protopines.I have always assumed that the protoberberines were the saturatedprecursoralkaloids (proto- meaning early or source) which upon aro-matizationgave the berberines with an aromatic ring "c." It now looksasifthe entire group is often simply called the protoberberines. In thefour-ringprotoberberine with the ring "C" aromatized, the hydroxyla-tionof the carbon atom that was the original N-methyl group leads to

XXVI The Simple Plant Isoquinolines

a group of compounds called 8-oxy (or 8-oxo) berberines. This tauto-meric interconversion is shown above.

If there is a hydroxy group as well as a benzyl group on the I-posi-tion and there are two N-methyls in the THIQ ring (the quaternarysalt), another family can be explored through this 2,N-Me attack. Thesealkaloids are of the protopine class, but to understand their structureslittle tautomeric manipulation is needed.

an ortho (2,N-Me) attack Tautomeric equilibrium

A tautorner is a bit of structural sophistication. One can move theelectrons around, without moving any of the atoms, and some end upwith quite a different looking thing. Which is it? It's a bit like theproblem with the duality of the photon. It is a particle and it is a wave,both. It pretty much depends on how you look at it. The middle struc-ture, with an 0- and an N+, should be rather soluble in water. It is anionic doubly charged molecule, after all. But the structure on the rightis a ketone and an amine, and would probably be lipophilic, andwouldn't dissolve in water. Is it water soluble? Hard to use that as away of telling the structure because just the act of putting it in watermight shift the electrons towards the ionic configuration. As they sayin quantum mechanics, you can't observe anything without changingit in some way. These compounds will be portrayed in the 4-ring struc-ture with the 0- shown as a hydroxy group in the structural index.

Introduction xxvii

Pavines

The ortho (2,3) attack

The pavine family, created by the ortho-3 attack, has an unusualproperty not shared by any other isoquinoline group. The pavine canbe viewed in either of two ways, left to right, or right to left. This isbest seen in the above structural diagram on the right. View the left-handbenzene ring as the aromatic ring of the THIQ, and then go to thefirst carbon atom at the 4 0'clock position. The nitrogen bond in thecenterdemarks the second ring of the isoquinoline, with the I-positionbeing the point between these two locations, at the bottom. The car-bonbond out to the right of this point shows the benzyl group.

Now view the right-hand benzene ring as the aromatic ring of theisoquinoline,and then go to the carbon atom at the 10 0'clock position.The nitrogen bond in the center demarks the second ring of theisoquinoline; the point above is the I-position, and the carbon bondout to the left is the benzyl group.

Thus any pavine with different substituents on the two benzenerings could result from an ortho (2,3) attack of either of two differentisoquinolines. These items are entered both ways in this book. And inthe caseof pavines here, and the isopavines below, if there is a methylgroup on the nitrogen, it will be represented by the abbreviation Meinstead of CH3.

XXV111 The Simple Plant Isoquinolines

Isopavines4

1 4~ 2I

~

~

The ortho (2,4) attack

Unlike the pavines, the unusual internal N-bridged heterocycle ofthe isopavines admits to an isoquinoline classification in just one di-rection.

Morphanans

The ortho (2,4a) attack

This ortho-4a attack, forming the carbon skeleton of the morphinemolecule, is one that is not easily visualized by non-chemists. It re-quires an out-of-plane manipulation to bring the benzyl group into con-junction with the ring-juncture 4a carbon atom. The I-benz yl-isoquinoline is shown in its conventional form on the left. To picturethe attack, mentally take hold of the benzyl group and bring it back,

Introduction XXIX

out of the plane of the paper, to where the 2-position is pointing di-rectlyat the 4a-position. This is the only one of the ortho attacks that issuperficially not an oxidation. The consequence is that the aromaticresonancestatus of the benzenoid ring of the THIQ is permanently lost.Thelocation of the residual double bonds and other electrons dependstotally on the substitution pattern of the isoquinoline aromatic ring.Once the attack has been achieved, the plant world makes many fur-ther chemical steps, leading to a host of alkaloids related to thebaineand morphine, both of which contain an additional heterocyclic furanring. They lie beyond the scope of this compila tion. An unna tural, butfascinating compound is the (+) isomer of the product of this attackwith a 4-methoxybenzyl on the I-position, a methyl on the nitrogen,and hydrogenation of the resid ual benzene ring of the pa ren tisoquinoline. This product is the broadly abused antitussive,dextromethorphan, or DXM.

Another family of alkaloids, the Hasubanans, are often lumped to-getherwith the Morphinans beca use of a superficially similar morphol-ogy. As an illustration:

HO

CHsO

CHsOo OCHs

Sinoacutine (a Morphinan) Cepharamine (a Hasubanan)

They are actually indoles, not isoquinolines, and so they are notincluded in this listing.

xxx The Simple Plant Isoquinolines

Azaluoranthenes

The ortho (2,8) attack (with a 1-phenyl)

Although most ring-substituents on the 'l-position of the naturaltetrahydroisoquinolines are substituted benzyl groups or isobenzo-furanones, occasionally a phenyl grou p is observed, bound directly tothe isoquinoline ring. An ortho (2,8) attack leads directly to theindino[l,2,3-ij]isoquinolines, known commonly as the azafluoranthenes.

Aporphines

The ortho (2,8) attack (with a 1-benzyl)

This family is viewed as an ortho-attack on the S-position of theisoquinoline ring. This produces a four-ring system known as anaporphine.

Well over a hundred years ago it was discovered that morphine,when treated with a strong acid, gave rise to the compound apomor-phine, an aporphine. It is now known that the lower of the two aro-matic rings of apomorphine is the result of the rearomatization of thebenzyl group, which was compromised by the ortho-4a attack men-

Introduction XXXI

tionedabove. But at the time it was thought to be a simple conversion,and for a long while the structure of apomorphine was thought to rep-resentthe skeleton of morphine itself.

Cularines

The ortho (2,8-0H) attack

Hereis the generation of a 7-membered oxygen-containing heterocycle.

Proaporphines

The (1,8) attack

This is a Ll-spirobenzyl intermediate to what is quite likely theentire family of the aporphines. The "pro" part of the name suggeststhat this is a biosynthetic precursor to these alkaloids. Very often thereis a keto function at the 4-position of the benzyl group (equivalent to ahydroxyl group on the original benzyl), to facilitate the spiro loss ofaromaticityneeded to achieve this type of coupling. This is directlyanalogousto the (2,4a)attacks needed to get into the morphinans, where

XXXll The Simple Plant Isoquinolines

a ketonic presentation of an aromatic hydroxyl group permits the bond-ing to occur.

5-p hen y lfurano [2,3,4- ijIisoq uino 1ines

/OH/8-HO a-H

The a,B-HO attack

There are several reports of tetrahydroisoquinolines with a fusedfuran ring that could be argued (for the sake of the classification usedin this collection) as an oxidative attack by the a-hydrogen of the 1-benzyl onto the 8-HO substituent, in a manner similar to the formationof a seven-membered ether ring seen in the cularines. It can also beseen as a similar oxidative attack from an a-hydroxy group (a com-monly encountered benzyl substituent) on the 8-hydrogen position. Thefirst of these two mechanisms (illustrated above) is used in this collec-tion.

THE SECOISOQUINOLINES

The prefix "seco" is an unusual term occasionally encountered inthe literature of natural products. Just as the term "or tho-attack" indi-cates the generation of a new ring, the term "seco" indicates the de-struction of a ring. A secoisoquinoline is formed from a 1-substitutedtetrahydroisoquinoline by the loss of the 1,2-bond. Transferring a hy-drogen atom from the a-carbon to the nitrogen, and reshuffling theelectrons, results in the formation of a new double bond.

Introduction

Phenethylamines

a a

1,2 seeo bond loss

Inan appendix to the book "TIHKAL: The Continuation" there werelisteda number of the phenethylamines known to be in the cactus fam-ily. Thesewere all of classical simplicity with the phenyl ring substi-tuted with one or more hydroxys and methoxys, and an occasionalmethylenedioxy group. There was also an occasional hydroxy groupon the beta position of the chain, and on the nitrogen atom there werezero, one, or two methyl groups. There was no mention made of asubclassof phenethylamines which are intimately associated with theisoquinolines. The chemical term "seco" is a clever device for main-taining a structural relationship between two chemicals after having,magically,removed a structural bond. Illustrated here is an aporphinewith the electrons from that l,2-bond having been rearranged into themiddle ring. It would probably be chemically classified as anaminoethyl-substituted phenanthrene, rather than a phenethylaminewhich had been fused (2,3a) with a naphthalene, but in this book itwill be listed in the section describing the parent I-benzyl-tetrahydroisoquinoline, modified with an ortho attack if appropriate,followedby a l,2-seco bond removal.

XXX111

XXXIV The Simple Plant Isoquinolines

With the simpler l-benzyl derivatives (those which have not un-dergone any ortho-attack), the removal of the 1,2-bond usually pro-duces a 2-styryl substituted phenethylamine. Again, this would be lo-cated in the entry that described the parent isoquinoline.

The second illustration above is a phthalide THIQ, and thesephenethylamines are sometimes referred to as secophthalide-isoquinolines. Here, the oxygen atom of the original isofuranone ringis substituted on the newly formed double bond. This structure caneasily open up to the corresponding ketonic carboxylic acid. These seco-modifications of the attacked isoquinoline (first example, illustratedwith an aporphine) and the simpler I-substituted isoquinolines (sec-ond example, as illustrated by the isobenzofuranone) are the only onesincluded in this book. The standard phenethylamines that are com-monly found in cacti, compounds which are not from these seco-mecha-nisms, have been tabulated in TIHKAL and will not be repeated here.

There have been many compounds excluded from this compila-tion, but to give examples would increase the mass of this collectionwithout any useful information. They are, in a general hand-wavingsense, those compounds not explicitly allowed in the above inclusioncriteria.

To all rules, there are always exceptions. These have been made toallow unexpected natural isoquinolines that just happen to presentunexpected substituents that nature for some reason chose to contrib-ute to this collection. Mention has been made of an occasional carbo-nyl group disrupting the aromaticity of the benzene ring (this is thebasis of the quinonic isoquinolines). The nitrogen atom (position 2)occasionally displays an amide group (these have been entered at thefourth letter of the structural alphabet). Several natural compoundsdemand a hydroxyl or methoxyl function at the isoquinoline 3- or 4-positions. When this occurs, the compound is listed as a footnote un-der the parent structure.

More difficult to generalize, are the isoquinolines with new ringsresulting from biosynthetic attacks from here to there that are excludedfrom this study. In a broad, inclusive statement the line has again beendrawn to exclude everything that has not been included above.

Originally it was intended to list every plant in which these natu-ral isoquinolines are found, documented with a literature reference.The project became unmanageable in that some of the more commonalkaloids have been found in literally hundreds of plants. So, in somecases, if there are many species from one Genus, the plant listing willbe condensed to mention the particular Genus, the family, plus a lit-erature reference; e.g., Corydalis spp. (Papaveraceae) jnp 51, 262 '88.This way the broadness of distribution is established. Also, there are

Introduction xxxv

sectionsin the structural index where there is a compound that hasoneormore synonyms. In some instances, synonyms of what are sup-posed to be the "same" compound have been given different lists ofplants. So, it could be that different names are given to represent dif-ferentoptical isomers, we don't know. But in most cases the differen-tiation was respected, the lists of plants to a given name were keptseparatewithin a given section.

Formuch of the plant information we are most grateful for beingallowedaccess to the NAPRALERT (sm) database at the University ofIllinoisat Chicago, and would highly recommend the use of their ser-vicesif more detailed information is wanted. In particular, we appre-ciate the help of Douglas Trainor there. Also, we'd like to give greatthanksto Jim Bauml, the Senior Biologist at the Arboretum of Los An-gelesCounty, for helping to resolve many plant name and family is-sues,Amy Rasmussen for her supurb proofreading skills, and FraniHalperin for her artwork on the cover of this book.

Trivial Name Index

TRIVIAL NAME INDEX

Acetonyl-reframidineN-AcetylanolobineN-AcetylanonaineN-AcetylanhalamineN-AcetylanhalonineN-AcetylasimilobineD-AcetylfumaricineN-AcetyllaurelliptineN-AcetyllaurolitsineN-Acetyl-3-methoxynornantenineN-Acetyl-3-methoxynornuciferineN-AcetylnomantenineN-AcetylnomuciferineN-Acetyl-seco-N -methylla urotetanineN-AcetylstepharineD-AcetylsukhodianineN-AcetylxylopineActinodaphnineAcutifolidineAdlumiceineAdlumiceine enol lactoneAdlumidiceineAdlumidiceine enol lactoneAdlumidineAdlumineAducaineAequalineAlborineAlkaloidFk-5AlkaloidPO-3Allocryptopinea-AllocryptopineAlpinone

I

312263252431445571651336840739622917219618128226928485

24324334434434024113970

45010896

327327223

2 The Simple Plant Isoquinolines

AmurensineAmurensinineAmurineAmurinol IAnalobineAnaxagoreineAnhalamineAnhalidineAnhalinineAnhalonidineAnhalonineAnhalotineAnibacanineAnicanineAnisocyclineAnnocherine AAnnocherine BAnnolatineAnnonelliptineAnolobineAnomolineAnomuricineAnomurineAnonaineAobamineAobamidineApocavidineApocrotonosineApocrotsparineApoglaziovineAporeineAporheineAporpheineArgemonineArgemonine me tho hydroxideArgemonine N-oxideArgentinineArgentinine N-oxideArizonineArmepavineArosineArosinine

2923011541552625942943143943244343293175403104105107388262388376399246324344157601001032482482482132182145656354178152133

Trivial Name Index

Artabonatine AArtabonatine BArtavenustineAryapavineAsimilobineAsimilobine- 2-0-~-D-glucosideAtherolineAtherospermidineAtherosperminineAtherosperminine N-oxideAurotensineAyuthianineBackebergineBaicalineBelemine2-Benzazinel-BenzylisoquinolineBerberastineBerbericineBerbericinineBerberilycineBerberineBerberrubineBerbervirineBerbineBerbin-8-oneBerbithineBerbitineBerlambineBernumicineBemumidineBemumineBerolineBharatamineBicucullineBicucullinidineBicucullinineBiflorineBisnorargemonineBoldineBoldinemethiodideBracteoline

2554106344954551994111721721142611614242643939

29929721030029728532440

2853213212995316553

28591

342243345329

71, 1226768138

3


BreoganineBromcholitinBulbocapnineBulbocapnine methiodideBulbocapnine N-oxideBulbodoineBuxifolineCaaverineCalifomineCalifomidineCalycinineCalycotomineCanadalineCanadinea-Canadine~-CanadineCanadinic acidCanelillineCapaurimineCapaurineCapaurine N-oxideCapnoidineCapnosineCapnosinineN-CarbamoylanonaineN-CarbamoylasimilobineN-CarboxamidostepharineCarlumineCamegineCarpoxidineCaryachineCaryachine methiodideCaseadineCaseadine N-oxideCaseadinium quatCaseamineCase amine N-oxideCaseanadineCaseanidineCaseanineCassamedineCassameridine

34921428628828632641291

311314318166296296296296324934364374373409016225157182242164305

82,28783,288

365365365362362364364207419317

CassyfilineCassyformineCassythicin eCassythidineCassythineCatalineCatalpifolineCavidineCeltineCeltisineCephakicin eCephamonineCephamulineCephasugineCerasodineCerasonineChakranineCheilanthifolineCherianoineCinnamolaurineCissaglaberrimin eCissamineOarkeanidineClaviculineCoclanoline BCoclaurineCocsarmineCodamineCodamine N-oxideColchiethanamineColchiethineColletineColumbamineConstrictosin eCoptisineCorarnineCoreximineCorftalineCorgoineCorledineCorlumidineCorlumine

Trivial Name Index 5

4154152874184152172052303633494264284284261371471978142727538212835934919197

2041411418585

10614342309121121335898686242


CorphthalineCorunnineCorybrachylobineCorybulbineCorycavidineCorycavamineCorycavineCorycularicineCorydaldineCorydalidzineCorydalineCorydalisolCorydalispironeCorydalmineCorydalmine methochlorideCorydalmine N-oxideCorydecumbineCorydineCorydine methineCorydine N-oxideCorydinineCorygovanineCoryrnotineCorynoxidineCorypallineCorypalmineCoryphenanthrineCoryrutineCorysamineCorysolidineCorystewartineCorytenchineCorytenchirineCorytensineCorytuberineCoryximineCotarnineCotarnolineCoulteroberbinoneCoulteropineCrabbineCrassifoline

33515222179

328331331353239722203213322022212033351431521453291542212098874217338315157326196196340120325447445448448194359


Crassifoline methineCrebanineCrebanine N-oxideCristadineCrotoflorineCrotonosineCrotsparineCrotsparinineCrychineCrykonisineCryprochineCryptaustolineCryptocavineCryptodorineCryptopineCryptopleurospermineCryptostyline ICryptostyline IICryptostyline IIICryptowolidineCryptowolineCryptowolinolCucolineCulacorineCularicineCularidineCularidine N-oxideCularirnine

Cularine Cularine N-oxideCyclanolinel a-Cyclanolinet p.cyclanolineIDanguyelline

l~DasymachalineDauricoside Decumbenine Decumbenine-CC Decumbensine epi~-Decurnbensine~lucopterocereine

Deglucopterocerelne N-oxide

361281281134996099993111781791462333072333341671671688215415865

34935335035136336636612812812837730563

335334340340372372


Dehassiline1,2-Dehydroanhalarnine1,2-Dehydroanhalidinium quat1,2-DehydroanhalonidineDehvdroanonaineDehydroboldineDehydrocapaurimineDehydrocavidineDehydrocheilanthifolineDehydrocorybulbineDehydrocorydalineDehydrocorydalmineDehydrocorydineDehydrocorypallineDehydrocorytenchineDehydrocrebanineDehydrodicentrineDehydrodiscretamineDehydrodiscretineDehydroformouregineDehydroglaucentrineDehydroglaucineDehydroguattescine1,2-Dehydroheliarnine1,2,3,4-DehydroheliamineDehydroisoboldine3,4-DehydroisocorydioneDehydroisocorypalmineDehydroisolaurelineDehydroisothebaine1,2-DehydrolemaireocereineDehydrolirinidineDehydronantenineDehydroneolitsine6,6a-Dehydronorglaucine6,6a-DehydronorlaurelineDehydronomuciferine1,2-Dehydronortehuanine1,2-DehydronorweberineDehydronuciferineDehydroocopodineDehydroocoteine

1084304324332476743723081792212031468819628130270763961462162711611611272381432689537092227312206277169391455171323417


1,2-Dehydropach ycereine1,2,3,4-Dehy dropach ycereine1,2-Dehydropellotinium quatDehydrophanostenineDehydrophoebineDehydropredicentrineDehydropseud och eilanthifo lineDehydroremerinea-DehydroreticulineDehydroroemerine1,2-Dehydrosalso lidineDehydrostephalagineDehydrostephanineDehydrostesakineDehydrothalicmineDehydrothalicsimidineDehydroxylopineDehydroxyushinsunineDelporphine6-O-Demethyladlumi dine6-O-DemethyladlumineN-Demethy lamurine8-DemethylargemonineDemethylcoclaurineN-Demethylcolletine1Q-O-Demethylcoryd ine3'-0-Demeth ylcularine1Q-O-Demethyldiscretinen-0-Demeth yldiscretineDemethyleneberberineN-Demethy lfumaritine0-7' -Demethy 1-l3-hydrastine9-O-DemethylimeluteineN-Demethy lisocorytuberineN-Demethyllinoferine04-Demethy lmurarnine3'-Demethylpa paverine7-DemethylpapaverineN-Demethylstephalagine3-0-Demethy lthalicthuberine2-Demethylthalimonine9-Demethylthalimonine

4564574352934067815425011425016440926028041740226724837816086153

147,2034710513736071665015733539313420120019014040984

237,42384,423


10-Demethylxylopinine 203Densiberine 217Deoxythalidastine 2677-0-Desmethylisosalsolidine 90Desmethylnarcotine 446O-Desmethylweberine 455N,O-Diacetyl-3-hydroxynornuciferine 375N,O-Diacetylisopiline 386N,O-Diacetylnoroliveroline 257Dicentrine 301Dicentrinone 306Didehydroaporheine 250Didehydroocoteine 417Didehydroglaucine 216Didehydroroemerine 2505,6-Dihydroconstrictosine 42Dihydrocoptisine 3095,6-Dihydro-3,5-di-O-methylconstrictosine 43Dihydroguattescine 271Dihydroimenine 3978,9-Dihydroisoroemerialinone 202Dihydro1inaresine 322Dihydromelosmine 3871,2-Dihydro-6,7-methylenedioxy-l-oxoisoquinoline 3333,4-Dihydro-l-methyl-5,6,7-trimethoxyisoquinoline 3923,4-Dihydronigellimine 1648,14-Dihydronorsa1utaridine 110Dihydronudaurine 155Dihydroorientalinone 13511,12-Dihydroorientalinone 135~-Dihydropallidine 124Dihydropalmatine 209Dihydroparfumi dine 165Dihydrorugosinone 3228,14-Dihydrosa1utaridine 119Dihydrosecoquettamine 3574,6-Dihydroxy-3-methoxymorphinandien-7-one 494,6-Dihydroxy-2-methyltetrahydroisoquinoline 413,9-Dihydroxynornuciferine 3765,6-Dimethoxy-2,2-dimethyl-l-(4-hydroxybenzy1)-I,2,3,4-THIQ quat 466,8-Dimethoxy-l,3-dimethylisoquinoline 3486,7-Dimethoxy-N,N-dimethyl-l-(2-methoxy-4-hydroxybenzy1)-THIQ 188

Trivial Name Index

1,2-Dirnethoxy-ll-hydroxyaporphine1,2-Dirnethoxy-3-hydroxynora porp hine1,2-Dirnethoxy-3-hydroxy-5-oxonora porphine2,9-Dimethoxy-3- hydroxypa vinane6,7-Dirnethoxy-l-(6',7 -methy 1enedioxyisobenzofurano1, 3'-y 1)-

2,2-dimethy1-1,2,3,4- THIQ6,7-Dimethoxy-l-(3,4-meth y1enedioxypheny 1)-2-methy 1-DHIQ6,7-Dimethoxy-l-(3,4-methy 1enedioxypheny 1)-2-methy 1-IQ6,7-Dirnethoxy-l-( 4-methoxybenzy l)-IQ6,8-Dirnethoxy-l-methyl-3- hydroxymethy lisoquinoline6,7-Dimethoxy- 2-met hylisocarbostyril6,7-Dirnethoxy-N -meth y lisoquinoline6,7-Dirnethoxy-2-methylisoquinolium quatN,o-Dimethy1actinoda p hnineN,o-Dimethy1armepavine0,o-Dimethy1bo1dineN,o-Dimethylcassyfiline0,0- Dimethylcissamine3,5-Di-O-methylconstrictosineO,o-Dimeth ylcorytuberineN,o-Dimethy lcrotonosineN,o-Dimethy lcrotsparineO,o-Dimeth ylcyclanolineN,o-Dimethy1hemovine0,0- Dimethy1isobo1dineN,o-Dimethy 1isocorydineN,N-Dimethy llindcarpineO,N-Dimethy lliriodendronine0,0- Dimethyllongifo1onine0,0' -Dimethy1magnoflorine0,o-Dimethy1munitagineN,o-Dimethy1nandigerineN,o-Dimethy1oreolineN,o-Dimethy1oridineN,N-Dimethy1pavinium quatN,o-Dimethy 1thaicanineDinorargemonineDisco1orineDiscretamineDiscretineDiscoguattineDomesticine

175373373

44,106

24416816818434824024016230118521432321843

21217917921876

2142186893

186218

212,371300180180218403

71,122487076

320155

11


DomestineDoryafranineDoryanineDoryfornineDoryphornineDoryphornine methyl etherDuguespixineDuguetineDuguevanineDuguexineDuguexine N-oxideDysoxylineEgenineElmerrillicineEnneaphyllineEpiberberineEpiglaufidine10-Epilitsericine6-Epioreobeiline14-EpisinomenineEpisteporphineEscholamidineEscholamineEscholidineEscholineEscholinine (also see under Romneine)EschscholtzidineEschscholtzidine methiodideEschscholtzineEschscholtzine N-oxideEschscholtzinoneEximineEvoeuropinea-FagarineFiliformineFissiceineFissicesineFissicesine N-oxideFissilandioneFissisaineFissistigine AFissistigine B

2262793341601602405830541926426423934041136022514527412466249293312293129303

225,301228,304

311311317301178327416289183183326378318348

Trivial Name Index

Fissistigine CFissoldineFK-3000FlavinantineFlavinineFloripavidineFloripavineFormouregineN-FormylanhalamineN-FormylanhalinineN-FormylanhalonidineN-FormylanhalonineN-FormylanonaineN-Formylbuxifoline7-Formyldeh ydro hernanergineN-Formyldehydronorn uciferine7-Formyldeh ydrothalicsimidineN-FormylduguevanineN-FormylhernangerineN-Formyl-0-meth ylan halonid ineN-FormylnomantenineN-FormylnornuciferineN-FormylovigerineN-FormylpurpureineN-FormylputerineN-FormylstepharineN-FormylxylopineFugapavineFumaflorineFumaflorine methyl esterFumaramidineFumaramineFumaricineFumaridineFumarilineFumarine

~ Fumaritine~ Fumaritine N-oxide[ Fumariz'" meJ FumarophycinolIFumschleicherineiFuzitine

13

14731842513813456118395430440436445251413290173405420294442229173314404269181269275236236243346165339283329108108324108346189


GandhararnineGentryamine AGentryamine BGigantineGindarineGlaucentrineGlaucineGlaucine methineGlaucine methiodideGlaucinoneGlaufidineGlaufineGlaufinineGlaunidineGlaunineGlauventGlauvineGlaziovineGnoscapineGorchacoineGortschakoineGoudotianineGouregineGovadineGovanineGroenlandicineGuacolidineGuacolineGuadiscidineGuadiscineGuadiscolineGuatterineGuatterine N-oxideGuattescidineGuattescineGuattouregidineGuattouregineGusanlungAGusanlungBGusanlungCGusanlungDn-Hainanine

18234834737320714321421921922214563201152199214152102452358358376455137146813183202652733204104102652713873882852974424879

Trivial Name Index

HeliamineHemiargyrineHenderineHernagineHernandia baseHernandia base IIHernandia base IVHernandia base VIIIHernandonineHernangerineHernovine (also see under Ovigerine)HexahydrofugapavineHexahydromecambrineHexahydrothalicminineHigenamine~-HomochelidonineHomolaudanosineHomolinearisineHomomoschatolineHumosine-AHunnemanineHydrastidineHydrastinea-HydrastineI}-HydrastineHydrastinimideHydrastinineHydrocotarnineHydrohydrastinine4-Hydroxyanonaine4-Hydroxybulbocapnine4-Hydroxycrebanine7-Hydroxydehydroglaucine3-Hydroxy-6a,7 -deh y dronuciferine8-Hydroxydehydroroemerine4-Hydro xydicentrine4-Hydroxyeschschol tzi dine3-HydroxyglaucineN-Hydroxyhernangerine41}-Hydroxyisocory dine2'-HydroxylaudanosinelO-Hydroxyliriodenine

16112244620129029030629231629069

27627641547

32723961

396340289335336337336339333447245247287281222374259302

235,382380294194234277

15


1o-Hydroxymagnocurarine13~-Hydroxy-N-rnethylstylopine quatHydroxynantenine3-Hydroxynantenine4-Hydroxynantenine3-Hydroxynornantenine4-Hydroxynornantenine3-HydroxynornuciferineN-Hydroxynorthalicthuberine3-HydroxynuciferineN-Hydroxyovigerine8-Hydroxypseudocoptisine4-Hydroxysarcocapnidine4-Hydroxysarcocapnine8-Hydroxystephenanthrine8-Hydroxystephenanthrine N-oxide13~-Hydroxystylopine3-Hydroxy-2,9,10-trirnethoxytetrahydroprotoberberine4-HydroxywilsonirineHyndarinHypecournineIrneluteineIrnenineIntebrirnineIntebrineIsoanhalarnineIsoanhalidineIsoanhalonidineIsoapocavidineIsoauturnnalineIsobackebergineIsoboldineIsocalycinineIsocanadineIsococlaurineIsocoptisineIsocorexirnineIsocorybulbineIsocorydineIsocorydine N-oxideIsocorydioneIsocoryne

1053182303812243802243732273743143113603652592593167414020733439339716333442742742784863701243183005931166150192194238336

IsocorypallineIsocorypalmineIsocorypalmine N-oxideIsocorytuberineIsocularineIsodomesticineIsofugapavineIsoguattouregidineIsohydrastidineIsolaurelineIsolaureline N-oxideIsomoschatolineIsonorargemonineIsonorteh uanineIsonorweberineIsooconovineIsoorien talinoneIsopachycereineIsopacodineIsopellotineIsopilineIsopycnarrhineIsoquinolineIsoremerineIsoroemerialinoneIsosalsolidineIsosalsolidine N-oxideIsosalsolineIsosalutaridineIsoscoulerineIsosendaverineIsosevanineIsosinoacutineIsotembetarineIsothebaidineIsothebaineIsouvariopsineIsovelucryptineIzmirinelaculadine[acularineJatrorrhizine

Trivial Name Index

5214114213736483

276384335268268375

77, 19439145638913545773

4283855239

24820116416490

1236552

2841373619495

2796287609975

17


[uziphine[uziphine N-oxideJuzirineKarnalineKikernanineKuafurnineKukolineLaetanineLaetineLarnbertineLanuginosineLastourvillineLatericineLaudaneLaudanidineLaudanineLaudanosineLaudanosolineLauforrnineLaunobineLaurelineLaurelliptineLaurepukineLaurifolineLauroli tsineLauroscholtzineLaurotetanineLauterineLedeborineLedecorineLernaireocereineLeonticineLeucolineLeucoxineLeucoxylonineLeucoxylonine N-oxideLirnousarnineLinaresineLincangenineLindcarpineLinearisineLiridinine

35535610057

202414656980

3032735010219119119120749

2742842791112631326419519027915732337035739

3214214213513223796461

383

LiridineLirinidineLirinineLirinine N-oxideLiriodendronineLiriodenineLirioferineLiriotulipiferineLitsedineLitseferineLitsericineLitsoeineLongifolidineLongifolonineLongimammamineLongimammatineLongimammidineLongimammosineLophocereineLophocerineLophophorineLophotine saltLotusineLuteanineLuteidineLuxandrineLysicamineMachiglineMachilineMadeyineMacrantaldehydeMacrantalineMacrantoridineMagnococlineMagnocurarineMagnoflorineMagnoporphineMajarineManibacanineMarshalineMecambridineMecambrine


39692

3743744725720472

295290274190370100454245419191

444444621921594917028997

329451449449358104129218297175324450275


MecambrolineMelosmidineMelosmineMenisperineMescalotama-N -MethopapaverberbineMethoxyatherosperminineMethoxyatherosperminine N-oxideI-Methoxyberberine10-Methoxycaaverine3-Methoxyglaucine3-MethoxyguattescidineMethoxyhydrastine10-MethoxyliriodenineIl-Methoxyliriodenine3-Methoxynordomesticine3-Methoxynuciferine3-Methoxyoxoputerine13-Methoxy-8-oxyberberine4-MethoxypalmatineMethoxypolysignine3-Methoxyputerine8-MethoxyuvariopsineN-MethylactinodaphnineN-Methyladlumine3-MethylallocryptopineO-MethylanhalidineN-Methylanhalidine quatO-MethylanhalonidineN-Methylanhalonidinea-8-MethylanibacanineN-MethylanolobineO-MethylanolobineN-MethylanonaineN-MethylapocrotsparineN-Methylarmepavineo-MethylarmepavineO-Methylarmepavine N-oxideN-MethylasimilobineN-Methylasimilobine-2-0-~-D-glucopyranosideN-Methylasimilobine-2-o-a-L-rhamnopyranosideO-Methylatheroline

276399387197442448395395447105402412452279273390395414305403217412282287242328440432441434942632662481031811851855555561220

Trivial Narne Index

N-MethylboldineQ-MethylbracteolineN-MethylbulbocapnineQ-Methylbulbocapninea-Q-Methylbulbocapnine N-oxide~O-Methylbulbocapnine N-oxideN-MethylbuxifolineN-MethylcalifomineN-MethylcalycinineQ-Methy1calycinineN-MethylcanadineQ-Methy1capaurineQ-MethylcaryachineN-Methylcaryachinium quatN-MethylcassyfilineQ-MethylcassyfilineN-MethylcassythineQ-MethylcassythineN-Methylcheilanthifoline quatQ-MethylcinnamolaurineN-MethylcoclaurineQ-7-Methy1coclaurine13-Methylcolumbarnine3-Q-Methy1constrictosineN-MethylcoreximineQ-Methy1corledineN-MethylcorydaldineN-Methy1corydaline quatN-Methylcorydalrnine quatN-MethylcorydineQ-Methy1corydineQ-Methy1corydine NsoxideN-MethylcorypallineQ-Methylcorypallinel-Methylcorypalline2-MethylcorypalliniumN-Methylcorypalrninell-MethylcorytuberineN-MethylcrotonosineN-MethylcrotsparineN-MethylcrotsparinineN-Methylcrychine

68149288300300300413314319320303442

225,30183,288

41541641541683

2791001761514313224123922120415121221289

162908979

14361

102103314

21


O-MethylcularicineN-MethylcularineN-MethyldanguyellineO-MethyldehydroisopilineN-Methyldihydroberberine quat0-Methyl-8,9-dihydroisoorientalinoneO-MethyldihydrosecoquettamineO-MethyldomesticineN-MethyldomesticiniumN-MethylduguevanineN-MethylelmerrillicineO-Methylelmerrillicine6,7-Methylendioxy-1-

Trivial Name Index

0-MethylisopilineN-MethylisopilineN-Methylisosalsoline1-0-MethylisothebaidineN-MethylisothebaineN-Methylisothebainium cation0-MethylisovelucryptineN-Methyllaudanidinium iodideN-MethyllauformineN-MethyllaunobineN-Methyllaurelliptine9-0-Methylla urolitsineN-MethyllaurotetanineN-Methyllaurotetanine N-oxideO-MethylledecorineN-Methyllindcarpine0-MethyllirinineN-MethyllitsericineN-Methyllophophorine quatN-Methylmecambridine2-Methyl-1-(4-methoxybenzyD-

6,7-methylenedioxyisoquinolinium quatN-Methyl-10-G-methylhernovineO-MethylmoschatolineN-MethylnandigerineN-Methylnandigerine ~-N-oxideN-MethylnantenineN-Methyl-a-narcotineO-MethylnarcotolineN-Methylneocaryachine quatD-Methylnorarmepa vine9-0-Methylnorboldine8-O-MethyloblongineN-Methyloreophiline saltD-MethylorientalinoneN-MethylovigerineN-Methyloxoh ydrasteineD-MethyloxopukateineN-MethylpachycereineN-MethylpachypodanthineN-Methylpachypodanthine N-oxideN-Methylpalaudium quat

27876

396292292228454452

288,36918473

371450201310339273457256256197

23

39438590

1759696

18919727628612473

19519632466

395276444450


O-MethylpallidineO-Methylpallidine N-oxideO-Methylpallidinine13-MethylpalmatineN-MethylpapaveraldineN-Methylpapaverine quatN-MethylpavineO-MethylpellotineN-Methylpellotine quat0-Methylpeyomvic acid0-Methylpeyoxylic acid0- MethylplatycerineN-Methylplatycerinium quat0-Methylprechilenine0-Methylpreocoteine0-Methyl przewalskiinone8a-Methylpseudoanibacanine8~-MethylpseudoanibacanineN-Methylpseudolaudanine0-MethylpukateineN-MethylputerineN-Methylsecoglaucine0-MethylseverzineN-MethylsinactineN-MethylsparsiflorineN-MethylstenantherineN-Methylstepharine0-MethylstepharinosineN-Methylstylopinium quata-N-Methylstylopinium quat~-N-Methylstylopinium quatN-Methyltetrahydrocolumbamine1-Methyl-1,2,3,4-tetrahydroisoquinolineN-MethyltetrahydropalmatineN-MethyltetrahydropapaverineN-Methylthaicanine0-MethylthaicanineN-Methylthalbaicaline0-MethylthalicmidineN-Methylthalidaldine0-MethylthalisopavineN-Methyl-2,3,6-trimethoxymorphinandien-7 -one N-oxide

147149149221220217213442435441441

212,371197,367

33240222094947826726721924122810339817918731331331315139218207380402380214408214149


N-MethylushinsunineG-MethylvelucryptineN-MethylviguineN-MethylxylopineN-Methylxylopine N-oxideN-MethylzenkerineMichelalbineMichelanugineMicheline AMicheline BMichepressineMiltanthalineMilthanthineMocrispatineMollinedineMoschatolineMunitagineMuramineNandazurineNandigerineNandinineNantenineNarceimineNarceineNarceine imideNarceinoneNarcosineNarcotinea-Narcotinep-NarcotineNarcotinediolNarcotine hemiacetalNarcotolineNarcotolinolNarlumicineNarlurnidineNeocaryachineNeolitsineNigellimineNigellimine N-oxideNokoensineNoramurine

25518624526826810625327025425727643617950307383

117,362222156290285226345454454454452452452453451452446446345345

286,368312164164437153


NoranicanineNorannuradhapurineNorargemonineNorarmepavineN-NorarmepavineNoratherosperminineNorboldineNorbracteolineNorbulbocapnineNorcanelillineNorcarnegineNorcinnamolaurineNorcoclaurineNorcorydineNorcorypallineNorcularicineNorcularidineNordelporphineNordicentrineNordomesticineNorfissilandioneNorfumaritineNorglaucineNorgorchacoineNorguattevalineNorimeluteineNorisoboldineNorisocorydineNorisocorydioneNorisocorytuberineNorisocularineNorisodomesticineNorjusiphineNorjuziphineN-NorlaudanosineNorlaurelineNorleucoxylonineNorliridinineNorlirioferineNornantenineNornarceineNorneolitsine

174280

147,2031761761716413428493163274471398835235037729515332515720635837639311118923713436380354354205277421383201223453307

NomuciferidineNomuciferineNomuciferine IO-NomuciferineNoroconovineNoroliveridineNoroliverineNoroliverolineNororientalineNororientinineNoroxyhydrastinineNorpachyconfineNorpachystaudineNorpallidineNorphoebineNorpredicentrineNorpreocoteineNorprotosinomenineNorpurpureineNorreframidineNorreticulineNorrufescineNorsalutaridineNorsarcocapnineNorsarcocapnidineNorsecocularidineNorsecocularineNorsecosarcocapnidineNorsecosarcocapnineNorsinoacutineNorsonodioneNorstephalagineNorstephanineNortehuanineNorthalicmineNorthalicthuberineNorthalifolineNorushinsunineNoruvariopsarnineNorweberineNoryuziphineNoscapalin


1731699255

40027027225313395

33258

25611140573

38963

401307109392110363359351366360364110237409260391416227159253186455354452


Noscapineu-NoscapineNoscopine hemiacetalNuciferidineNuciferinNuciferineNuciferolineNudaurineNummularineOblongineObovanineOchotensidineOchotensimineOchotensineOcobotrineOcokryptineOcominarineOcominaroneOconovineOcopodineOcoteineOcotominarineOcoxylonineOduocineOliveridine Oliveridine N-oxideOliverineOliverine N-oxideOliverolineOliveroline P-N-oxideOphiocarpineOphiocarpinoneOpianOpianineOreobeilineOreolineOreophilineOridineOrientalineOrientalinoneOrientidineOrientine

45245245217417017018115553

356262327238871204233254224013234174224204182702702722722542543053064524521249945099135135183184


OrientinineOureguattidineOvigerineOxoanolobineOxoasimilobine7-oxobaicaline8-oxoberberrubineOxobuxifoline8-0xocanadineOxocompostelline8-0xocoptisineOxocrebanine13-0xocryptopineOxocularidineOxocularicineOxocularine7-0xodehydroasimilobineOxodicentrineOxoduocineOxoglaucineOxohydrastinineOxoisocalycinine8-0xoisocorypalmineOxolaurelineOxolaurenine 'Oxo-N -methylhydrasteine13-0xomuramineOxonantenineOxonuciferineOxophoebine8-0xopolyalthiaine13-0xoprotopineOxopukateineOxopurpureineOxoputerineOxosarcocapnidineOxosarcocapnineOxosarcophyllineOxostephanineOxostephanosine8-0xotetrahydropalmatine8-0xotetrahydrothalifendine

963863062665842528541429736931028323335235336858

306419220333319142279279339223231170407158331266404273362367352261259209291


8-0xothaicanineOxoushinsunineOxoxylopineOxyberberineN-Oxycodamine8-0xycoptisineOxydehydrocorybulbineN-OxyduguexineN-OxyguatterineOxyhydrastinineN-OxyoliveridineOxynarcotineN-OxypachyconfineOxypalmatine13-0xyprotopineN-Oxyspixianine8-0xythalifendinePachycereinePachyconfinePachyconfine N-oxidePachypodanthinePachystaudinePacodinePalaudinePallidinePallidinine'Palma tinePalmatrubinePancoridinePancorininePapaveraldinePapaveraldinium quatPapaverinePapaveroxidinePapaveroxinePapaveroxinolinePapracinePapracininePaprafuminePaprainePapralineParfumidine

37925727329914131080

26441033327045359211331319292456595925625714019012312421019214014021922020645245145133910734651245166

ParfuminePavinePecteninePellotinePeruvianinePeshawarinePessoinePetalinePetaline methinePeyoglutamPeyophorinePeyorovic acidPeyotine quatPeyotlinePeyoxylic acidPhanosteninePhellodendrinePhoebe basePhoebe base IIPhoebinePhyllocryptinePhyllocryptoninePilocereinePlatycerinePolyalthinePolyberbinePolycarpinePolygosperminePolysigninePolysuavinePrechileninePredicentrinePreocoteinePreocoteine N-oxidePrepseudopalmanineProaporphinePromucosinePronuciferineProtopineProtosinomenineProtothalipinePseudoanibacanine

Trivial Name Index

1072051644341763451093583574384454344354344342931326662

406288289240

192,36541332123540518626532977

3893892234018217932965

20094

31


PseudoberberinePseudocheilanthifolinePseudocolumbaminePseudocoptisinePseudojatrorrhizinePseudolaudaninePseudomanibacaninePseudopalmatinePseudoprotopinePseudorinePseudoroninePsilopinePterocereinePukateinePulchinePurpureinePuterinePycnarrhineQuettamineRaddeanamineRaddeanidineRaddeanineRaddeanoneRefractamideReframidineReframineReframine methiodideReframolineRehybrineRemerinRemerineRemerine N-oxideRemerolineRemrefidineRemrefineReticulineReticuline N-oxideRhopalotineRoefractineRoehybrineRoemecarineRoemecarine N-oxide

3001541463117673175213331787841137226310640226688

35723223223123230731122622883135248248249263250228111114145621357474


n-RoemehybrineRoemeramineRoemerialinoneRoemerineRoemerine N -oxideRoemerolidineRoemerolineRoemrefidineRoemrefineRogersineRomneine (also see under Escholinine)RomucosineRomucosine GRomucosine HRotundineRufescineRugosinoneRurrebanidineRurrebanineSalSalsolidineSalsolineSalsolinolSalutaridineSalutaridine N-oxideSalutarineSanjoinine IaSanjoinine IbSanjoinine ESanjoinine KSarcocapnidineSarcocapnidine N-oxideSarcocapninecis-Sarcocapinine N-oxideSarcophyllineSauvagnineSaxoguattineSchefferineScoulerineSebiferineSecocularidineSecocularine

136275201248249264263250228195295252404199

71,122,20739332237539647163524711811911816918917097

359360364364350323200202114147351367


SecoglaucineSecophoebineSecoquettamineSecosarcocapnineSecosarcocapnidineSecoxanthoplanineSendaverineSendaverine N-oxideSetigeridineSetigerineSevanineSeverzineSewerzineSiamineSiaminineASiaminine BSibiricineSinactineSinacutineSinoacutineSinococulineSinomendineSinomenineSonodioneSparsiflorineSpermatheridineSpiduxineSpinosineSpixianineSpixianine N-oxideSplendabolineSplendidineSrilankineStenantherineStephabinamineStephabineStephadiolamine 13-N-oxideStephalagineStephanineStepharanineStepharineStepharinosine

2174063573673611988989231222153160160347347347317224118118426416523810025723618831931939817478

398436438255409260136177187


StephenanthrineStephenanthrine N-oxideStephodelineStepholidineSteporphineStesakineStesakine-9-0-l3- D-glucopyranosideStipitatineStylophyllineStylopineSuavedolSuaveolineSubsessilineSukhodianineSukhodianine-~-N-oxideTakatonineTannagineTaxilamineTehuanineTehuanine N-oxideTelazolineTeliglazineTelikovineTelitoxineTembetarineTepenineTetradehydrocapaurineTetradehydrocheilanthifolineTetradehydroscoulerineTetrahydroberberineTetrahydroberberrubineTetrahydrocolumbarnineTetrahydrocoptisineTetrahydrocorysarnineTetrahydrojatrorrhizineTetrahydropalmatineTetrahydropalmatrubineTetrahydropapaverineTetrahydroprotoberberineTetrahydropseudoberberineTetrahydrosinacutineTetrahydrostephabine

25125142913624928028037233730710218839828228240042923439139292

3861741671273714378111729628514130731574

20719120540

300120438


ThaicanineThailandineThaipetalineThalactamineThalbaicalidineThalbaicalineThalflavineThalicmidineThalicmidine methineThalicmidine N-oxideThalicmineThalicminineThalicsimidineThalicpureineThalicthuberineThalicthuberine N-oxideThalictricavineThalictricineThalictrimineThalictrineThalictrisineThalictuberineThalidastineThalidicineThalidineThalifaurineThalifendineThalifendlerineThalifolineThalihazineThalimicrinoneThalimonineThalimonine N-oxideThaliporphineThaliporphine methineThalisopavineThalisopynineThaliphendineThalphenineThalprzewalskiinoneTrichoguattineTriclisine

37926137840838037942514915215041741840240322822930429432712929422829113812382291399160407400

237,424237,424

149152194401291159200252166

Trivial Name Index

Tridictyophylline3,10,11-Trihydroxy-l,2-methylenedioxynoraporphineTrilobinine2,3,7-Trimethoxy-8,9-methylenedioxy-N -methyl pavinane5,6,7-Trimethoxy-N-methylisoquinolinium quat1,2,11-Trimethoxy-6a-noraporphine2,3,6-Trimethoxy-N -normorphinandien-7 -one1,2,3-Trimethoxy-5-oxonoraporphineN,O,O- TrimethyllaurelliptineN,O,O- TrimethylsparsiflorineTritopineTuduranineTuliferolineTurcamineTurcomanidineTurcomanineUberineUmbellatinUshinsunineUshinsunine l3-N-oxideUthongineUvariopsamineUvariopsamine N-oxideUvariopsineVaillantineVelucryptineVeronamineViguineWeberidineWeberineWilsonirineWorenineXanthalineXanthopetalineXanthoplanineXanthopuccineXyloguyellineXylopineXylopinineXylopinine N-oxideYenhusomidineYenhusomine

438382158

235,41639218313939421418519117839635418810946

2972542542831871872685110639924544

456139316219292198296384266212213234234

37


Yuanhunine 205Yuzirine 100Yuziphine 355Zanoxyline 185Zanthoxyphylline 184Zenkerine 105Zijinlongine 449Zippelianine 428Zizyphusine 51

Structural Index - Unsubstituted 39

UNSUBSTITUTED ISOQUINOLINES

IsoquinolineLeucoline

2-Benzazine

Cistanche salsa (Orobanchaceae) yh 8, 522 '88Nicotiana tabacum cv (Solanaceae) abc 41, 377 '77Papaver somniferum (Papaveraceae) abf 21, 201 '84Spigelia anthelmia (Loganiaceae) pm 52, 378 '86

OQHI-Methy l-l,2,3,4-tetrah ydroisoq uinoline

Pachycereus weberi (Cactaceae) ac 57, 109 '85

I-Benzylisoquinoline

\ benzyl IH IQ

Thalictrum spp. (Ranunculaceae) yfz 10,72 '90


benzylMe THIQ

8,8a-SecoberbineNot a natural product.syn 9, 887 '92

Iwith a (2,N-Me) attack: ITetrahydroprotoberberine

Berbine

Berberis beaniana (Berberidaceae) tl25, 951 '84Fumaria officina lis (Papaveraceae) abs 4

4-HO-benzylMe THIQ

Compound unknown

Iwith a (1,8) attack: IProaporphine

Phoebe formosan a (Lauraceae) pptp 27, 65 '93

Structural Index - Monosubstituted

5-SUBSTITUTED lSOQUINOLINES

Compound unknown5-MeO2,3-MeO ,MeO-u,u- M e,HO-benzylH IQ

Iwith a (6,8) attack: I

Sinomendine

Sinomenium acutum (Menispermaceae)jnp 57, 1033 '94

6-SUBSTITUTED ISOQUINOLINES

6-HOHMe THIQ

H0Yi(l~NCH3

Longimammosine

Dolichothele longimamma (Cactaceae) joe 41,319 '76

OH

HO~

~~CH3

Iwith a 4-hydroxy group: I4,6-Dihydroxy-2-

methyltetrahydroisoquinoline

Theobroma cacao (Sterculiaceae) llyd 41, 130 '78

41


6-HO Compound unknown4-HO-benzyl, HOMe THIQ

with a (2,N-Me) attackand loss of hydrogen:

HO

OH

5,6-Dihydroconstrictosine

Aristolochia constricta (Aristoloehiaeeae)aa 13, 737 '83

Iwith a 3,4-ene: I HO

OH

Constrictosine

Aristolochia constricta (Aristolochiaceae)aa 13, 737 '83

6-MeOHH THIQ

Longimammatine

Dolichothele longimamma (Cactaceae) joe 41, 319 '76Dolichothele uberiformis (Cactaceae) joe 41, 319 '76


Not a natural product.tet 37, 3175 '81

6-MeO4-HO-benzyl, HOMe THIQ

with a (2,N-Me) attack,loss of hydrogen,and a 3,4-ene:

3-0-Methylconstrictosine

Aristolochia constricta (Aristolochiaceae) aa 13, 737 '83

Not a natural product.joc 44, 3730 '79

6-MeO4-MeO-benzyl, HOMe THIQ

with a (2,N-Me) attackand loss of hydrogen:

5,6-Dihydro-3,5-di-O-meth ylconstrictosine


Iand a 3,4-ene: I

3,5-Di-O-methylconstrictosine


43

OH



7-HO4-HO-benzylH THIQ

Compound unknown

with a 1,2 seco,with an N-carbomethoxy:

Gusanlung C

Arcangelisia gusanlung (Menispermaceae)phy 39, 439 '95

HO

Weberidine7-MeOHH THIQ

Pachycereus weberi (Cactaceae) ac 57, 109 '85

Compound unknown7-MeO3,4-MeO,HO-benzylMe THIQ

Iwith a (6,3) attack: I

2,9-Dimethoxy-3-hydroxypavinane

CH30

Argemone munita (Papaveraceae) joe 38, 3701 '73

also under: 6,7 MeO HO R Me THIQR= 4-MeO-benzyl (2,3) attack



Longimammidine8-HOHMe THIQ

Dolichothele longimamma (Cactaeeae) joe 41, 319 '76Dolichothele uberiformis (Cactaeeae) llyd 40, 173 '77Theobroma cacao (Sterculiaceae) llyd 41, 130 '78

Iwith a 4-hydroxy group: I

Longimammamine

Dolichothele longimamma (Cactaeeae) joe 41, 319 '76Dolichothele uberiformis (Cactaeeae) llyd 40, 173 '77

~NCH3

OH

OH

q)NCH3OH

45


5,6-DISUBSTITUTED ISOQUINOLINES

5-MeO 6-MeO4-HO-benzylMe,Me+ THIQ

5,6-Dimethoxy-2,2-dimethyl-l-(4-hydroxybenzy1)-l,2,3,4- THIQ quat

Desmos yunnanensis (Annonaceae) tcyyk 12, 1 '00


Uberine5-MeO 7-HOHMe THIQ

Dolichothele uberiformis (Cactaceae) jnp 40, 173 '77


None found in plants

Structural Index - 6,7-HO,HO-Substituted

6,7-DIHYDROXYSUBSTITUTED ISOQUINOLINES

H0:GQ~ I S NHHO

CH3

6-HO 7-HOMeH THIQ

SalsolinolSal

Aconitum carmichaeli (Ranunculaceae) yx 17, 792 '82Musa paradisiaca (Musaceae) jafc 24, 189 '76Theobroma cacao (Sterculiaceae) jafc 24, 900 '76

Compound unknown6-HO 7-HOa-keto-benzylH IQ

HO

Iwith a (2,8) attack: I LiriodendronineHO

Liriodendron tulipifera (Magnoliaceae)phy 16,2015 '77

HOHigenamineNorcoc1aurine

Demethylcoc1aurine

6-HO 7-HO4-HQ-benzylH THIQ HO

HO

Aconitum carmichaelii (Ranunculaceae) kjp 29, 129 '98Aconitum japonicum (Ranunculaceae) jnp 44, 53 '81Aconitum koreanum (Ranunculaceae) kjp 29, 129 '98Aconitum kusnezoffii (Ranunculaceae) kjp 29, 129 '98

47


Aconitum napiforme (Ranunculaceae) kjp 29,129 '98Annona reticulata (Annonaceae) tl28, 1251 '87Annona squamosa (Annonaceae) jnp 44, 53 '81Asiasarum heterotropoides (Aristolochiaceae) cpb 26, 2284 '78Asiasarum sieboldii (Aristolochiaceae) cpj 44, 211 '92Euodia rutaecarpa (Rutaceae) book 1Gnetum parvifolium (Gnetaceae) jnp 62, 1025 '99Nelumbo nucifera (Nymphaeaceae) cpb 18,2564 '70

HO6-HO 7-HO4-HO-benzylMe THIQ

(d1)-N-Methylhigenamine

Gnetum parvifolium (Gnetaceae) jnp 62, 1025 '99

I the N-oxide: I(-)-N-Methylhigenamine N-Oxide

Gnetum parvifolium (Gnetaceae) jnp 62, 1025 '99

with a (1,8) attack,and reduction of a double bond and ofthe carbonyl group in the benzyl ring:

Discolorine

Croton discolor (Euphorbiaceae) rlq 1, 140 '70Croton plumieri (Euphorbiaceae) rlq 1, 140 '70

I the glucoside at the 7-0H position: I

N-Methylhigenamine, 7-0-[3- D-glucopyranoside

Phellodendron amurense (Rutaceae) phy 35,209 '94

HO

HO

HO

HO

Structural Index - 6,7-HO,HO-Substituted 49

6-HO 7-HO4-MeO-benzylMe,Me+ THIQ

HOLuxandrine

HO

Pseudoxandra sclerocarpa (Annonaceae) phy 25,2693 '86

6-HO 7-HO3,4-HO,HO-benzylMe THIQ

HO

HOLaudanosoline

Papaver somniferum (Papaveraceae) book 4 HO

OH

6-HO 7-HO3,4-HO,MeD-benzylH THIQ

Compound unknown

Iwith a (2,4a)attack: I

Croton bonplandianus (Euphorbiaceae)phy 20, 683 '81

4,6-Dihydroxy-3-methoxymorphinandien-7-one

o


Compound unknown6-HO 7-HO3,4-HO,MeO-benzylMe THIQ

Iwith a (2,4a) attack: I Mocrispatine

Monodora crispata (Annonaceae) aua 17, 105 '81

o

TetrahydroprotopapaverineNot a natural product.jcspt 2, 1696 '80

6-HO 7-HO3,4-MeO,MeO-benzylMe THIQ

with a (2,N-Me) attackand aromatization of the c-ring:

HO

OCH3

HO

Demethyleneberberine OCH3

Stephania venosa (Menispe

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The Simple Plant Isoquinolines