RODD'S CHEMISTR Y

OF CARBON COMPOUND S

A modern comprehensive treatis e

SECOND EDITION

Edited by

S . COFFEYM.Sc. (London), D.Sc . (Leyden), C .Chem., F.R.I .C.

formerly ofI.C.I. Dyestuffs Division, Blackley, Mancheste r

VOLUME IV PART L

HETEROCYCLIC COMPOUND S

Fused-ring heterocyclic compounds containing three or more nitroge natoms ; purines and related ring systems, nucleosides, nucleotides and nuclei cacids ; pteridines, alloxazines, flavins and related compounds. The bio-

synthesis of plant alkaloids and nitrogenous microbial metabolites

Heterocyclic Compounds : Fused-ring heterocyclic compounds containing three or morenitrogen atoms ; purines and related ring systems ; nucleosides, nucleotides and nucleicacids ; pteridines, alloxazines, flavins and related compounds . The biosynthesis of plant

alkaloids and nitrogenous microbial metabolites

PREFACE VII

OFFICIAL PUBLICATIONS ; SCIENTIFIC JOURNALS AND PERIODICALS XIV

LIST OF ABBREVIATED NAMES OF CHEMICAL FIRMS MENTIONED IN PATENT REFERENCES .

X V

LIST OF COMMON ABBREVIATIONS AND SYMBOLS USED XVI

Chapter 57. Purines and Related Ring Systemsby G. SHA W

1 . Purities, imidazolo[4,5-d]pyrimidines 1a. General introduction 1b. Synthetic methods

4(i) Synthesis from pyrimidines, 5 - (ii) From imidazoles, 15 - (iii) Abiogenicsynthesis, 22 - (iv) Other syntheses, 25 -

c. Purine and alkylpurines

2 7

(i) Purine, 27 - (ii) C-Alkylpurines, 28 - (iii) N-Alkylpurines, 29 -

d. Hydroxypurines

30(i) Monohydroxypurines, 31 - (ii) Dihydroxypurines and their derivatives, 32 -(iii) Uric acid, 2,6,8-trihydroxypurine, 36 - (iv) N-Alkylhydroxypurines, 42 -(v) Alkoxypurines, 51 -

e. Halogenopurines

52

(i) Methods of preparation, 52 - (ii) Properties and reactions, 55 - (iii) Individualhalogenopurines, 60 - (iv) Chlorohydroxypurines and their N-substitute dderivatives, 62 -

f. Mercaptopurines

62

(i) Synthesis, 62 - (ii) Properties and reactions, 64 - (iii) Individual purinethiols ,65 -

g. Aminopurines

69(i) Methods of preparation, 70 - (ii) Properties. 72 - (iii) Individual amino-purines, 73 -

h. Aminohydroxypurines 8 3i. Nitropurines and related compounds 84j. Purine N-oxides

8 8(i) Purine 1-oxides, 88 - (ii) Purine 3-oxides, 90 - (iii) Purine 7- and 9-oxides ;7-hydroxypurines, 91 -

k. Spectra of purines

9 6

(i) Ultraviolet, 96 - (ii) Infra-red, 98 - (iii) Proton magnetic resonance spectra ,98 - (iv) Mass spectra, 99 -

1 . Paper- and thin-layer-chromatography of purines 100

2 . Thiazolopyrimidines 100a. Thiazolo[5,4-d]pyrimidines 10 1

(i) Synthesis, 101 -

b. Thiazolo[4,5-d]pyrimidines 102

3 . Pyrazolopyrimidincs 103a. Pyrazolo[3,4-d]pyrimidines or 1,2,5,7-tetra-azaindencs 10 3

(O Synthesis . 103 - (ii) Properties, 105 -

b. Pyrazolo[4,3-d]pyrimidines or 1,2,4,6-tetra-azaindenes

107

(i) Synthesis, 107 - (ii) Properties. 108 -

4 . vie,-Triazolo[4,5-d]pyrimidines (8-azapurincs)

10 9

0) Synthesis . 109 - (ii) Properties. 112 -

Chapter 58 . Nucleosides, Nucleotides and Nucleic Acidsby D. S .

E s

1 . Nucleosides 11 7

a. Structure of nucleosides 11 8

(r) The nature of the sugar, 120 - (it) The size of the sugar ri n g , 121 - (iii) Positionand configuration of the glycosidic linkage, 121 -

b. Synthesis of nucleosides 12 5(i) Methods of synthesis . 125 - (ii) Stereochemical and mechanistic considera-tions . 133 -

c. Properties of nucleosides

I3 5

(i) Reactions of the bases, 135 - (ii) Reactions of the sugar moiety . 136 --

d. Individual nucleosides 13 9

2. Nucleotides 14 6a. Structure of nucleotides 14 8b. Synthesis of nucleotides 15 2

(i) Ribonuclcoside 5'-phosphates, 152 - (ii) Ribonucleoside 2'- or 3'-phosphates .155 - (iii) Ribonucleoside and 3',5'-dinhosnhates, 156 - (iv) Deoxyribu-nucleoside 5'-phosphates. 156 - (r) Deoxyribonucleoside 3'-phosplates. 157 -(vi) Cyclic phosphates . 158 -

c, Identification of nucleosides and nucleotides 159

3 . Nucleotide coenzymes 1 62(f) Nucleoside di- and tri-phosphates, 163 - (ii) The pyridine coenzymes, 166 -(iif) Flavin-adenine dinucleotide (FAD) . 170 -- (iv) Coenzyme A, 172 - (r) Nucle-oside diphosphate sugars . 17 5

4. Nucleic acids 18 1a. Isolation of nucleic acids 182b. Structure of nucleic acids 18 6

(1) Primary structure of DNA . 186 - (if) Secondary structure of DNA, 192 -(fii) Tertiary structure of DNA, 196 - fir) Primary structure of RNA, 199 -(v) Secondary structure of RNA . 206 -- (vi) The tertiary structure of RNA . 213 -

c. Synthesis of polynucleotides 21 5d. Properties of nucleic acids 229

Chapter 59 . Pteridines, Alloxazines, Flavins and Related Compoundsby K. OHTA, R. WRIGGLESWORTH and H. C . S. WOO D

1 . Pteridines 23 7a. Synthesis and preparative methods 23 8

(i) From pyrimidines, 238 - (ii) From pyrazines, 241 -

b. General properties

242(i) Physical properties, 242 - (ii) General chemical properties, 243 -

c. Pteridine and its derivatives 24 5(i) Pteridine, 245 - (ii) Pteridine homologues, 246 - (iii) Halogenopteridines ,247 - (iv) Aminopteridines, 248 - (v) Oxo(hydroxy)pteridines, 250 - (vi) MethoxY -pteridines, 254 - (vii) Mercapto- and alkylthio-pteridines, 254 - (viii) Amino-pteridinones, 255 - (ix) Pteridinecarboxylic acids, 262 - (x) Pteridine glycosides ,264 - (xi) Pteroylglutamic acid, pteroic acid and related compounds, 265 -

d. Hydropteridines

26 9(i) Dihydropteridines, 269 - (ii) Tetrahydropteridines . 272 -

e. Biosynthesis of dihydropteridines 27 32 . Alloxazines and flavins 27 5

a. Synthesis 27 5b. Chemical properties 278c. Alloxazines and homologues 280d. Riboflavin and related compounds

28 1(i) Biosynthesis, 285 - (ii) Chemical properties, 286 -

e. Flavin phosphoric acid derivatives 28 8

Chapter 60. The Biosynthesis of Plant Alkaloids and Nitrogenous Microbial Metabolitesby R . B . HERBER T

1 . Introduction 29 12. Pyrrolidine alkaloids 29 1

a. Tropane and related alkaloids 29 1b. Nicotine

299(1) The pyrrolidine ring, 299 - (ii) The pyridine ring, 303 -

c. Pyrrolizidine alkaloids 30 5d. Phenanthroindolizidine and related alkaloids 30 7

3 . Piperidine alkaloids 30 9a. Alkaloids derived exclusively from acetate 30 9b. Alkaloids derived from lysine 31 2

(i) Simple piperidine bases, 312 - (ii) Tetrahydroanabasine alkaloids, 320 -(iii) Lythraceae alkaloids, 322 - (iv) Lycopodium alkaloids, 323 - (v) Quino-lizidine alkaloids, 326 - (vi) Pipecolic acid and slaframine, 329 -

4. Pyridine alkaloids 33 15 . Bases derived from the tryptophan pathway 33 6

a. Gramine 33 6b. Dimethyltryptamine derivatives 33 8c. Indolmycin 33 9d. Pyrrolnitrin 340e. Sporidesmin 341

f. ß-Carboline alkaloids 342g. Calycanthine and folicanthine 343h. Isoprenoid indole bases 343

(i) Echinulin and brevianamide, 343 - (ii) Cyclopiazonic acid, 345 - (iii) Ergo talkaloids, 346 - (iv) Terpenoid indole alkaloids, 356 -

i. Phenoxazinones 36 9j. Damascenine 370k. Quinoline alkaloids 37 1

(i) Echinorine, 371 - (ii) Pseudans, 371 - (iii) Furocuinoline and relate dalkaloids, 372 -

I . Acridone alkaloids 376m. Graveoline 376n. Quinazoline alkaloids 377o. Rutaecarpine and evodiamine 379p. Benzodiazepine bases 379q. Benzoxazinones 38 1r. Phenazines 38 1s. Shihunine 38 5

6 . Bases derived from phenylalanine and tyrosine 38 6a. Introduction 38 6b. Amaryllidaceae alkaloids 38 8c. Mesembrine alkaloids 39 8d. Isoquinoline alkaloids 400

(i) Phenethylamines and simple isonuinolines, 400 - (ii) Phenylisocluinolinealkaloids . 405 - (iii) Benzylisonuinoline alkaloids, 406 - (iv) Phenethyliso-auinolines, 426 - (v) Miscellaneous. 430 -

7 . Miscellaneous types 43 8a. Dolichotheline 43 8b. Tenuazonic acid 43 9c. Azetidine-2-carboxylic acid 440d. Prodigiosin 441e. Phomazarin 44 2f. Nybomycin 44 2g. ß-Lactam antibiotics 44 3h. Mitomycins, geldanomycin, rifamycins and streptovaricins 44 6i. Steroidal alkaloids 449j. Terpenoid alkaloids 452

Index 457