CHEMICAL EDUCATION : ELEMICIN, A PHENYLPROPANOID ISOLATED FROM SPARATTANTHELIUM AMAZONUM, AS A DIDACTICAL EXAMPLE OF STRUCTURAL ELUCIDATION

REVISTA BOLIVIANA DE QUÍMICA The Bolivian Journal Of Chemistry VOLUMEN 19, No.1 - 2002

CHEMICAL EDUCATION :

ELEMICIN, A PHENYLPROPANOID ISOLATED FROM SPARATTANTHELIUM AMAZONUM, AS A DIDACTICAL EXAMPLE OF STRUCTURAL

ELUCIDATION

José Antonio Bravo;a* Michel Sauvainb

aLaboratorio de Química de Productos Naturales IIQ-IRD, Instituto de Investigaciones Químicas, Universidad Mayor de San Andrés,

CP 303, La Paz Bolivia; bInstitut de Recherche pour le Développement (ex-ORSTOM), 213 rue Lafayette, 75480 Paris cedex 10 *Corresponding author: [email protected]

Key Word Index: Sparattanthelium amazonum; Hernandiaceae; stem-bark; structural elucidation; Chemical Education. RESUMEN A partir de cortezas de tronco de Sparattanthelium amazonum (Hernandiaceae), elemicina, un fenilpropanoide fue aislado y caracterizado por técnicas espectroscópicas. En la investigación de productos naturales, el debutante se ve abrumado por el uso extensivo de las técnicas de RMN 2D. No son abundantes en la literatura los ejemplos de una aplicación global de estas técnicas, en particular con la presentación de los espectros, de manera que pretendemos ilustrar su uso sistemático a través de la elucidación estructural de la elemicina. ABSTRACT Starting from the stem bark of Sparattanthelium amazonum (Hernandiaceae), elemicin, a phenylpropanoid was isolated and characterized by spectrometric techniques. In the investigation of natural products, the beginner is overwhelmed by the extensive use of the techniques of 2D NMR. They are not abundant in the literature the examples of a global application of these techniques, particularly showing the spectra themselves, so that we seek to illustrate their use in a systematic way through the structural identification of elemicin. INTRODUCTION Among the works on the search of antiparasitic, antibacterial and antifungal vegetal active principles that we have been pursuing, the species Sparattanthelium amazonum Martius (Hernandiaceae), has been surveyed. This species, in a previous research, revealed containing the antimalarial alkaloid (-)-roemrefidine.1 In the present investigation, the petrol extract of the stem bark

permitted after application of a VLC chromatography the isolation of elemicin. The structure was deduced from NMR analysis and confirmed by EIMS. The small family Hernandiaceae, gathers five genus, four of them are trees (Gyrocarpus, Hernandia, Illigera and Valvatera) and the last one consist of lianas, (Sparattanthelium). In Bolivia, two genus have been found: Sparattanthelium (seven species identified) and Hernandia.2 Chemical studies showed that aporphinic alkaloids are ubiquitous in the family. Isoboldine, nandigerine,3 N-methylnandigerine,4 N-methylhernovin,5 isocoridin6 and hernangerine6 have been reported as constituents of species belonging to genus Hernandia. Gyrocarpus americanus7, 8 possess benzylisoquinoleine alkaloids like O-methyl limacusine and limacine, this one has been tested against paludisme. Illigera pentaphylla6 possess actinodaphnine and laurotetanine. The leaves of S. amazonum are used in decoction by the Chacobo Indians against vomits, diarrhea and general stomachaches.9

RESULTS AND DISCUSSION How to deal with a structural problem starting from the set of NMR spectra? Interpretation must follow a logic sense starting from 1DNMR information. A primary but careful analysis of the proton and 13C spectra gives rich and unique information to identify structural elements of the molecule. This elements’ description can be still enriched by data afforded by NMR multi - pulse experiments in one of or both of the frequencies in play, such as the DEPT experiment in the case of the 13C data for example. In order to make clearer some ideas regarding the more precise nature of these elements and in a prospective manner, the 2DNMR spectra can be surveyed. An exhaustive analysis of the 2DNMR homo and hetero nuclear distant and close connectivities will permit to establish the final pathway for the elements evoked

25


from the primary structural analysis, giving so the researched structure. A first qualitative and external approach to elemicin let appreciate some physical characteristics like its oily appearance and its deep aromatic smell, pointing out a possible phenolic or a monoterpenique structure. The final structure was established by the

application of most of the 2D NMR arsenal available. The discussion will be based in the description of a method to interpret the set of NMR spectra acquired. An analysis by electronic impact mass spectrometry confirms through the molecular peak and following molecular fragments the proposed structure by the NMR analysis.

H

H

1'

16'

5'

4'3'

2'

1'

CH30

CH30

CH30 13

2

H-3 H-3'

The 1HNMR spectrum.-permits to distinguish centered at δ 3.33 (2H,chemical shift gives information that correspdirectly bonded to amethylene with chemicwould show a singlet, hcloser look to the signadouble triplet for twononequivalent protons sconstant of 17.0 Hz and Then the signal is defin17.0 Hz, J3, 2= 6.7 Hz, Habove. Two intense singlets corgroups substituting distinguishable, the deshielded at δ 3.84 (6correspond to two meth

17

6.7

Geminal coupling (Hz)

Vicinal coupling (Hz)

17

6.7 6.7

H-3/H-3'

H-3/H-2, H-3'/H-2

Elemicin 1HNMR spectrum, 250 MHz, CDCl3

At first sight, this spectrum a broadened doublet peak

d, J3,2= 6.7 Hz, H-3). This already by itself fruitful

onds to an allylic methylene n aromatic ring. Such a al shift equivalent protons

owever in the present case, a l proton reveals in reality a methylene chemical shift howing a geminal coupling a vicinal coupling of 6.7 Hz. ed as : δ 3.33 (2H, td, J3, 3’ = -3) The split pattern is shown

responding to three methoxy aromatic protons are

more intense and more H, s,CH3O-3’and CH3O-5’) oxy groups, the other singlet

appears at δ 3.82 (3H, s, CH3O-4’). In the spectral portion δ 5.20 – 5.00 a grouping of peaks corresponding to ene protons appear, this ensemble will be depicted later in the text. The next signal is composed by a 10 rays signal shifted until δ 5.95 (1H, ddt, J2, 1 = 16.9 Hz, J2, 1’ = 11.0 Hz, J2, 3 = 6.7 Hz, H-2). This is another ene proton surely forming an ethylenic system with the protons described in the previously mentioned ene zone (δ 5.20 – 5.00). The ethylene is probably terminal, this presumption is confirmed by the DEPT 135 experiment that shows an ene methylene (=CH2) at 115.8 ppm This information let deduce already one extreme of the structure through the allyl just described (-CH2-CH=CH2). Also, the aromatic ring viewed from the chemical shift of the methylene of the terminal allyl grouping conduce to the other extreme of the molecule and we have in this manner, at least a methoxy phenyl propenoid at hand. The analysis of the complex split pattern (10 rays) of the vynilic

26


proton H-2 is as follows: A large coupling constant of 16.9 Hz with a trans ene proton (H-1), the coupling with the cis ene proton (H-1’) is defined as 11.0 Hz, finally two identical coupling constants were measured for the coupling of H-2 with CH2-3 giving a triplet of 6.7 Hz. Said this, the signal in the zone δ 5.20 – 5.00 corresponding to the CH2 of the terminal ethylene is described, first for the H-1 as the signal at δ 5.10 (1H, ddd, J1, 2 = 16.9 Hz, J1, 3 = 3.3

Hz, J1, 1’ = 1.7 Hz, H-1) and then for H-1’ as the signal at δ 5.12 (1H, ddd, J1’, 2 = 11.0 Hz, J1’, 3 = 3.3 Hz, J1’, 1 = 1.7 Hz, H-1’). Such values for coupling constants explain a spin coupling system that includes a geminal vynilic coupling H-1/H-1’ (1.7 Hz), a vicinal cis ethylenic coupling H-1’/H-2 (11.0 Hz), a vicinal trans ethylenic coupling H-1/H-2 (16.9 Hz) and long distance (4J) allylic couplings between H-1 or H-1’ and CH2-3 of about 3.3 Hz.

H-2H-1 (H-1')

16.9 (11.0)

H-1

H-1’

The end of the protonfrequencies, shows an corresponding to a 3J uncsinglet shape at δ 6.40 (2aromatic ring presents 4protons (3 CH3O- groupleaving place for onlBecause of the presence owe can presume, in the athis singlet includes twsymmetrical position in only the mass spectrum wbetween a monomeric or d The 13C NMR spectrumspectrum can be differenapplying the experiment Dbased in its generation on13CNMR spectrum (BBshows the nature of thephase the peaks for a Cputting out of phase (invepeaks) the signals for

6.7 Hz, H-2/CH2-3

16.9 Hz, H-2/trans H-1

3.3 (3.3)

N

aouH, s

ingy f obseo

theillim

.- tiaEP thD

cH

rse th

11.0 Hz, H-2/cis H-1’

1.7 (1.7)

MR spectrum at high romatic proton signal pled proton cause of its s, H-2’ and H-6’). The ubstituents of aromatic s and an allylic group) two aromatic protons. nly one aromatic singlet nce of the integral, that aromatic protons in a structure. At this point permit us to distinguish eric structure.

The nine peaks of this ted in their assignment T 135. This experiment, e broad band decoupled ) previously acquired, arbon atom, putting on 3 and CH carbons and sense to the CH3 or CH e CH2 carbons. The

quaternary carbon signals disappear in the DEPT spectrum. In a parallel approach to the proton spectrum, we can say that signals for more saturated hydrocarbons will appear at lower frequencies (high field) more to the right zone, and more unsaturated carbons will appear at high frequencies (low field) more to the left zone, in the 13CNMR spectrum. Then a comparative analysis of both 13C spectra, gives at high field a methylene at δ 40.4 (t, C-3), the multiplicity t from triplet correspond to the H-C coupling split pattern in an imaginary H-C broadband coupled 13CNMR spectrum. The chemical shift of this methylene corresponds to an allylic methylene. Two signals for three methyl ether groupings are present at δ 55.9 (q, MeO3’ and MeO5’) and δ 60.6 (q, MeO4’), q means quartet. Again as in the proton spectrum, the fact of having one signal for two groups of protons points out to a symmetrical structural disposition of such elements. These signals are the corresponding to the methoxy singlets in the proton spectrum. The relative intensity of a signal is indicative of a number of protons resonating at the same frequency. So, for methyl singlets, this relative

27


intensity gives an idea on the number of methyls for each singlet. At lower field appears an aromatic methyne (CH) at δ 105.3 (d, C-6’ and C-2’) and a CH2 ene at à δ 115.8 (t, C-1). A CH ene carbon appears very deshielded cause of its proximity to the aromatic ring at δ 137.1 (d, C-2). The rest of signals present only in the full 13CNMR spectrum are quaternary carbons all of them aromatics according to their chemical shifts, δ 135.6 (s, C-1’), δ 136.2 (s, C-4’) and δ 153.0 (s, C-5’ and C-3’). Considering the

existence of three methyl ether groupings and an allyl substituents of aromatic protons established by the above proton and 13C NMR analysis, all of the quaternary carbons are necessarily aromatic. The 2D NMR experiment XHCORR of close H-C correlation shows as well the absence of cross peaks for this carbons suggesting its quaternary nature.

Elemicin 13CNMR spectra, (BBD and DEPT 135) 62.9 MHz, CDCl3

The set of 2D NMR spectra.-The most impressing and powerful tool in structural determination is 2D NMR. Its evolution much faster than any other spectral technique in organic chemistry is due to the versatility, richness and fullness of the information it provides.10 2DNMR permits to establish: a) the plane structure thanks to homonuclear (H-H) and heteronuclear (H-C) close (1J) and distant (2J and 3J) connectivities; and b) sometimes the definition of stereochemistry through besides H-C distant connectivities, through space H-H correlations giving so a complete information on chemical structure. The COSY spectrum.- A natural approach to 2D information begins with the COSY spectrum. A 1HNMR spectrum rich in spectral data, particularly coupling constants can be reflected in a more explicit manner in the COSY spectrum. The COSY experiment permits to solve the two basic limitations associated to proton decouplings,10 the decoupling technique was, until the advent of COSY, the tool used to establish the vicinal protons existence. First, the homonuclear decoupling acquires a more and

more non selective comportment of irradiations as the structure and thence the proton spectrum becomes more complex. And secondly, a very overwhelmed cluster of signals where through a monodimensional proton spectrum no much information of proton vicinal disposition can be extracted due to absence of clarity for definition of split patterns and coupling constants, can be easily resolved by homonuclear correlations depicted by cross peaks in a two dimensions graphic. For elemicin, signals for H-1 and H-1’ are an ensemble of three multiplets centered at 5.1 ppm. From a theoretical stand point each proton should exhibit a triple doublet: a large trans ethylenique coupling, a medium size long distance allylic coupling, and a small geminal ethylenique coupling. The measure of coupling constants forces to the assignment for H-1 of δ 5.10 ddd (16.9, 3.3, 1.7 Hz) and for H-1’ of δ 5.12 ddd (11..0, 3.3, 1.7 Hz). The COSY spectrum shows a stack plot with cross peaks that permit to remark the geminal relationship between H-1 and H-1’. This spectrum shows also clearly, the vicinal correlation between H-2 and H-1/1’, and the

28


long distance coupling (4J ) between the aromatic couple of protons 6’/2’ and the methylene CH2-3. This cross peak let relate the two structural elements

previously evoked : the aromatic ring and the terminal allylic group.

H

H

H

H

H

C

3,3 Hz

3,3 Hz

16,9 Hz

11,0 Hz

1,7 HzH2

1'

16'

5'

4'3'

2'

1'

CH30

CH30

CH30 13 2

Elemicin: COSY correlations

The XHCORR spectrum.- And its analog experiments HMQC and HSQC highly utilized because of the powerful information it provides. Through the 2D graphic it is possible to establish the direct heteronuclear (H-C) correlation. This means that every proton can be related to the carbon supporting it, becoming thus an invaluable tool in total assignment of the carbon spectrum. The XHCORR spectrum of elemicin shows cross peaks for all protons and hydrogenated carbons in the

structure. The only exception is H-2 δ 5.95 (1H, ddt, J2, 1 = 16.9 Hz, J2, 1’ = 11.0 Hz, J2, 3 = 6.7 Hz) that lacks of correlation with C-2 due to the diminished intensity of H-2 signal provoked by its high multiplicity (10 rays), anyway the COLOC spectrum shows such a peak. In the XHCORR spectrum graphic, a spot has been added to make it more explicit, and so more didactical.

29


Elemicin: XHCORR spectrum

The COLOC spectrum.- This spectrum analog of the HMBC experiment, conducts to the assembly of the different structural elements and so to the establishment of the hydrocarbon skeleton. This can be done through the cross peaks 2JXH and 3JXH, that are present in the two dimensional graphic. This graphic makes evident four cross peaks corresponding to distant correlations for H-3 resonating at δ 3.33 (2H, d, J3, 2= 6.7 Hz). These

peaks establish connections between H-3 and C-2 (δ 137.1, d), C-1’ (δ 135.6, s), C-1 (δ 115.8, t) and C-6’/C-2’ (δ,105.3, d). It means that the methylene CH2-3 is surrounded by a sp2 hybrid systems: three CH, one CH2, and a quaternary carbon. The only manner to ensemble these elements justifying thus the correlation peaks is the following:

H2

H

H

HH

CC

H

CC

C

C

2

2'

6'1'

1

3J

3J

3J

3

CD: Direct Coupling

Elemicin: COLOC correlations

It must be noticed that the three methoxy groupings, are far enough form H-3 to suggest the absence of a distant correlation 2JXH or 3JXH. However we must indicate at this point that this not presence of neither 2JXH nor 3JXH cross peaks only suggests the absence of a correlation but it doesn’t ensure such a distant enough spatial nuclear disposition within the structure. Also, we notice the chemical shift equivalence of carbons and protons 2 and 6,

imposing thus a symmetric moiety in the molecule that must be in accordance to a free rotation about the axe C-1’ - C-3. In the next step in this correlation pathway of the hydrocarbon skeleton we look for correlations either between H-2’/H-6’ and next carbon atoms or between C-2’/C-6’ and next protons in order to find new structural references. Thus in the 2D spectrum H-2’/H-6’, δ 6.40 (2H, s) are related to two quaternary sp2 carbons besides C-1’, and these

30


are : C-5’ and C-3’ (s) at δ 153.0, and δ C-4’ (s) at δ 136.2. Considering the structural symmetric moiety mentioned, these correlations permit to close the six membered aromatic ring. Obviously from the three methyl ether groupings (CH3O-), two of them chemical shift equivalents, must be placed on quaternary carbons that are correlating exactly to H-

2’ and H-6’. To corroborate this symmetric substitution pattern, those correlations like δ 3.84 (6H, s,MeO3’and MeO5’) and δ 153.0 (s, C-5’ and C-3’), and like δ 3.82 (3H, s, MeO4’) and δ 136.2 (s, C-4’) appear as cross peaks in the contour plot of the COLOC experiment.

Elemicin: EIMS spectrum

The electronic impact mass spectrum- This technique even destructive regarding the sample, gives valuable information and some times complements the structural elucidation achieved by the different highly performing NMR tools. First advantage over NMR is due to the relative much less quantity of sample necessary for analysis. Secondly, EIMS solves the question about dimeric possible structures invisible to NMR techniques providing a peak M.+ corresponding to the molecular mass of the substance under survey. A series of fragmentations from M.+, gives a sequence of peaks in decreasing m/z values that correspond to parts of the molecule. The molecular fragments give a final idea about the global structure. For elemicin, the formula deduced from the NMR analysis, C12H16O3, fits well with the molecular mass given by the peak M.+ at m/z 208. The most significant subsequent fragments can be explained with partial structures in the following pathway. From the molecular peak M.+ at m/z 208, the peak at m/z 193 correspond to the loss of 15 m/z units ([M].+ - Me), sequentially the loss of a carbonyl is appreciated at m/z 165 (193 - CO).

O

- CO+

m/z 193

CH30

CH30

.+- .CH3

.+

m/z 208

CH3-0

CH30

CH30

The next fragmentation step involves a methyl loss and then a carbonyl loss with peaks at m/z 150 (165 - Me) and m/z 122 (150 - CO).

O

- CO.

+

m/z 150

CH30- .CH3

..+

m/z 165

CH3-0

CH30

+

m/z 122

CH30

From the molecular peak m/z 208 the peak at m/z 181 represent the loss of a vynil-H ([M].+ - CH2=CH).

-.CH=CH2.+

.+

m/z 208CH30

CH30

CH30

+

m/z 181

CH30

CH30

CH30

Finally from [M].+, separation of oxymethylene generates m/z 178 ([M].+ - CH2O) and m/z 177 ([M].+ - CH2O – H).

31


H

HC

O

-.CH2O

H2

.+

.+

m/z 208

CH30

CH30

H

H

H +

m/z 177

CH30

-.H.+

m/z 178

CH30

CH30CH30

Thus the structural elucidation demonstrated that the compound is a phenylpropenoid: 3-(3’,4’,5’-trimethoxy)-phenyl-1-propene or elemicin isolated previously from Uvariodendron connivens.11 The present paper constitutes an advance in spectral data for elemicin11, 12 being this the first report on 2D NMR (H-H and H-C COSY as well as long distance H-C correlations). Also some 1HNMR data has been enhanced regarding the literature, thanks to the higher frequency of the spectrometer we utilized. A possible biosynthetic route, derivates elemicin from L-phenylalanine or L-tyrosine coming from ammonia lyase or tyrosine ammonia lyase that after trimethoxydation gives the trimethoxy cynnamic acid. The acid is four times reduced on its acidic extreme to give the trimethoxy-phenyl-propane. A final oxidation produces the trimethoxy-phenyl-propene. EXPERIMENTAL

Sparattanthelium amazonum Martius

(Hernandiaceae). Illustration by C. Maldonado, LPB. NMR spectra were run in a AC 250 BRUKER spectrometer. Mass spectra acquired under electronic impact at 70 eV. VLC Alumina gel : 60 MERCK.

TLC plates: WHATMAN (250 and 500 µm, PK 6F, gel 60A). The stem bark of Sparattanthelium amazonum was collected in October 1993 in the Alto Beni region, Vaca – Diez province, Beni department in Bolivia. Voucher specimen is findable at the LPB Bolivian National Herbarium under SB-628, No. 819. 750 g of dried and pulverized stem bark was successively extracted in petrol (4 l, 24 hs.), then in CH2Cl2 (4 l, 24 hs.) and then in EtOH 95° (4 l, 72 hs.) in a Soxhlet apparatus. The petrol extract was treated in a VLC column in alumina gel using petrol, CH2Cl2 and CH2Cl2/MeOH as elution systems. Five fractions were obtained: fr. 1 petrol, 300 ml, fr. 2, 3 and 4 (CH2Cl2, 300 ml)X3 and fr. 5: CH2Cl2-MeOH (90:10), 300 ml. Fractions 2 and 3 (0,974 g, 0,13%) presented pure elemicin. Elemicin, 3-(3’,4’,5’-trimethoxy)-phenyl-1-propene: Oil, MS 70 eV, m/z (rel. int.) : 208 (100), 193 (88), 181 (35), 177 (59), 165 (55), 161 (27), 150 (50), 137 (20), 133 (54), 122 (25), 118 (43), 109 (18), 105 (37), 95 (16), 91 (34), 81 (10), 77 (24), 69 (19). 1HNMR (250 MHz, in CDCl3, δ 1H from TMS): δ 3.33 (2H, td, J3, 3’ = 17.0 Hz, J3, 2= 6.7 Hz, H-3); δ 3.82 (3H, s, CH3O-4’); δ 3.84 (6H, s,CH3O-3’and CH3O-5’); δ 5.10 (1H, ddd, J1, 2 = 16.9 Hz, J1, 3 = 3.3 Hz, J1,

1’ = 1.7 Hz, H-1) ; δ 5.12 (1H, ddd, J1’, 2 = 11.0 Hz, J1’, 3 = 3.3 Hz, J1’, 1 = 1.7 Hz, H-1’); δ 5.95 (1H, ddt, J2, 1 = 16.9 Hz, J2, 1’ = 11.0 Hz, J2, 3 = 6.7 Hz, H-2); δ 6.40 (2H, s, H-2’ and H-6’). 13CNMR (62.9 MHz, in CDCl3, δ 1C from CDCl3 at 77,0 ppm): δ 40.4 (t, C-3); δ 55.9 (q, MeO3’ and MeO5’); δ 60.6 (q, MeO4’); δ 105.3 (d, C-6’ and C-2’); δ 115.8 (t, C-1); δ 137.1 (d, C-2); δ 135.6 (s, C-1’); δ 136.2 (s, C-4’) ; δ 153.0 (s, C-5’ and C-3’). ACKNOWLEDGMENTS We thank the following persons and institutions for their collaboration to the present work. Dr. Sylvie Bergeron from IFEA for plant material and botanical characterization and the National Herbarium of Bolivia. Dr. Alberto Giménez and Lic. Patricia Mollinedo from UMSA. Prof. Catherine Lavaud and Mr. Philippe Sigaut from the University of Reims, for the mass spectrum. The French Government for the donation of the 250 MHz NMR spectrometer. The IFS for financial support. The FONAMA for project covering.

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REFERENCES 1 MUÑOZ, V., SAUVAIN, M., MOLLINEDO, P., CALLAPA, J., ROJAS, I., GIMÉNEZ, A., VALENTIN A., MALLIE, M. Planta Med., 1999, 65, 1-2 2 GENTRU, A. H., A Field Guide, The Families and Genera of Woody Plants of North West South America (Colombia, Ecuador, Perú), 1993,

Conservation International, Washington D.C. 3 GUINAUDEAU, H., LEBOEUF, M., CAVE, A. Lloydia, 1975, 38, 275-338. 4 CHALANDRE, M. C., BRUNETON J. J. of Nat. Prod., 1985, 49, 101-105. 5 CHALANDRE, M. C.,JACQUEMIN, H., BRUNETON J. J. of Nat. Prod., 1985, 48, 333. 6 ROSS, S., ROBERT, D., SHAMMA, M. J. of Nat. Prod., 1985, 48, 835-836. 7 DUTE, P., CHALANDRE, M. C., CABALION, P., BRUNETON, J. Phytochemistry, 1988, 27, 655. 8 BRANDAO M., BOTELHO M., KRETTLI A.

Ciencia y Cultura, 1985, 37, 1152-1163. 9 MOLLINEDO, P. P. A., GIMENEZ, A., SAUVAIN, M. Chemistry BS Thesis San Andrés Major Univesity, 1996, La Paz, Bolivia. 10 BRAVO J. A. The Bolivian Journal Of Chemistry, 2001, 18, 102-113. 11 MOHAMMAD, I., WATERMAN, P. G., THOMAS D. W.

J. Nat. Prod., 1985, 48, 328. 12 GIESBRECHT, A. M., FRANCA, N. C., GOTTLIEB, O. R. Phytochemistry, 1974, 13, 2285.

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Documents

CHEMICAL EDUCATION : ELEMICIN, A PHENYLPROPANOID ISOLATED FROM SPARATTANTHELIUM AMAZONUM, AS A DIDACTICAL EXAMPLE OF STRUCTURAL ELUCIDATION