Isolation of indole (β-carboline), pyridine, and indole–pyridine alkaloids from ...
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COMMUNICATIONS Isolation of indole (P-carboline), pyridine, and indole-pyridine alkaloids from Nauclea diderrichii STEWART MCLEAN AND D. G. MURRAY Department of C/zemistry, Unicersity of Toronto, Toronto, Ontario Received December 5, 1969 The bark of N. diderrichii has afforded alkaloids of novel structure and of biogenetic significance. Pyridines, a-carbolines, and more complex alkaloids that contain both of these units or modifications of them have been identified among the bases isolated. Canadian Journal of Chemistry, 48, 867 (1970) The genus Nauclea (Sarcocephalus) of the Rubiaceae appears to have attracted relatively little phytochemical interest in the past (1). We have now isolated a considerable number of bases, each in low yield, from the bark of Nigerian N. diderrichii. The alkaloids were separated by thin-layer chromatography (t.l.c.), their molec- ular formulae were determined mass spectro- metrically, and as many spectroscopic charac- teristics were recorded as the amounts of material obtained would allow. Structures deduced on the basis of these data were in most cases confirmed by synthesis, but in some of the more complex cases structural assignments are still incomplete. We have identified pyridines, P-carbolines, and alkaloids that incorporate both an indole com- ponent, apparently tryptamine-derived, and a pyrid~ne component that may be of terpenoid origin. Although the first reports of the co- existence of both pyridine and "C,,-indole" alkaloids in a single plant have appeared recently (2), the indole-pyridine alkaloids we describe appear to constitute a new structural class. This structural novelty and the potential biogenetic significance of the isolation of all 3 classes of alkaloids from a single plant lead us to give a preliminary account of our results. (i) Simple Pyridines Four 5-substituted derivatives of methyl nicotinate (la-d) were obtained, and each was synthesized from nicotinic acid through the ketone le, m.p. 90-92", by standard methods. The natural materials la-c were optically active and all, including Id, were obtained as oils, as were the racemic synthetic products; identity was therefore demonstrated by comparison of spectroscopic and t.1.c. characteristics. qR2 R1 2 a R1 = CH3;Rp = H b R1 = C02Me; R, = H c R1 = CH3; R2 = C02Me d R1 = CONHZ; R2 = H (ii) Simple P-Carbolines Three P-carbolines (2a-c), which have been described previously (3), were obtained. Harman (2a) is readily available and comparison samples of 26 and 2c were synthesized by established procedures (4). From one extraction, which employed ammonia, 2d was isolated; this was also obtained by the reaction of synthetic 2b with ammonia, and is therefore probably an artifact. 3 (iii) Indole-pyridine A lkaloids Three of the bases isolated have been placed with some confidenceill this group: C,,H, ,N,O,, Can. J. Chem. Downloaded from www.nrcresearchpress.com by SAN DIEGO STATE UNIVERSITY on 11/11/14 For personal use only.
Transcript of Isolation of indole (β-carboline), pyridine, and indole–pyridine alkaloids from ...
COMMUNICATIONS
Isolation of indole (P-carboline), pyridine, and indole-pyridine alkaloids from Nauclea diderrichii
STEWART MCLEAN AND D. G. MURRAY Department of C/zemistry, Unicersity of Toronto, Toronto, Ontario
Received December 5 , 1969
The bark of N. diderrichii has afforded alkaloids of novel structure and of biogenetic significance. Pyridines, a-carbolines, and more complex alkaloids that contain both of these units or modifications of them have been identified among the bases isolated.
Canadian Journal of Chemistry, 48, 867 (1970)
The genus Nauclea (Sarcocephalus) of the Rubiaceae appears to have attracted relatively little phytochemical interest in the past (1). We have now isolated a considerable number of bases, each in low yield, from the bark of Nigerian N. diderrichii. The alkaloids were separated by thin-layer chromatography (t.l.c.), their molec- ular formulae were determined mass spectro- metrically, and as many spectroscopic charac- teristics were recorded as the amounts of material obtained would allow. Structures deduced on the basis of these data were in most cases confirmed by synthesis, but in some of the more complex cases structural assignments are still incomplete. We have identified pyridines, P-carbolines, and alkaloids that incorporate both an indole com- ponent, apparently tryptamine-derived, and a pyrid~ne component that may be of terpenoid origin. Although the first reports of the co- existence of both pyridine and "C,,-indole" alkaloids in a single plant have appeared recently (2), the indole-pyridine alkaloids we describe appear to constitute a new structural class. This structural novelty and the potential biogenetic significance of the isolation of all 3 classes of alkaloids from a single plant lead us to give a preliminary account of our results.
( i ) Simple Pyridines Four 5-substituted derivatives of methyl
nicotinate ( la-d) were obtained, and each was synthesized from nicotinic acid through the ketone l e , m.p. 90-92", by standard methods. The natural materials la-c were optically active and all, including Id, were obtained as oils, as were the racemic synthetic products; identity was therefore demonstrated by comparison of spectroscopic and t.1.c. characteristics.
qR2 R1
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a R1 = CH3;Rp = H b R1 = C02Me; R, = H c R1 = CH3; R2 = C02Me d R1 = CONHZ; R2 = H
(ii) Simple P-Carbolines Three P-carbolines (2a-c), which have been
described previously (3) , were obtained. Harman (2a) is readily available and comparison samples of 26 and 2c were synthesized by established procedures (4). From one extraction, which employed ammonia, 2d was isolated; this was also obtained by the reaction of synthetic 2b with ammonia, and is therefore probably an artifact.
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(iii) Indole-pyridine A lkaloids Three of the bases isolated have been placed
with some confidenceill this group: C,,H, ,N,O,,
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868 CANADIAN JOURNAL OF CHEMISTRY. VOL. 48, 1970
m.p. 84-90", C,,H,,N,O,, m.p. 102-124", and C,,H2,N30,, m.p. 108-114". Structure 3. assigned to the first alkaloid, has been confirmed by its synthesis from tryptamine and If under Bischler-Napieralski conditions (5). Present data, which include hma,(MeOH) 224 (E 40 700), 276 (E 9500), 290 mp (sh, E 7900), hma,(CHC13) 5.80 p, a methyl singlet at T 6.14, and signals from 4 indole protons near .r 2.7 and 3 pyridine protons at T 1.03 (d, J -- 2 Hz), 1.48 (d, J 2 Hz), and 1.89 (3 lines, splitting - 2 Hz) in the nuclear magnetic resonance spectrum, indicate that the second is a tetracyclic secondary amine (acylable) and contains a simple indole unit and an isolated 5-substituted methyl nicotinate unit. The third appears, on the basis of data of a similar nature, to be a pentacyclic tertiary anline and to contain a simple indole unit and a disub- stituted (probably 4,5- ) methyl nicotinate unit.
(iz;) Other Alkaloids At least 6 other bases are present in the extract,
including C,,H,,N,02, m.p. 229-232" and C,,H2,N,0,, m.p. 209-211"; the former prob- ably belongs in group (iii), but it appears struc- turally more complex than those already assigned to that group. All extractions afforded a con- siderable amount of a coil~pon~vnt which had the characteristics of a high molecular weight polyhydroxy base.
The con~position of the total extract was variable and appeared to depend on factors such as the age of the tree from which the bark was obtained. The question of whether pyridines are
true alkaloids or artifacts produced by reaction of a precursor with ammonia during isolation has been raised previously (6). Our earlier procedures did employ ammonia in the extraction and chromatography steps, but, in a control isolation which carefully avoided ammonia at every stage, we obtained the same pyridine as in the former procedure; unfortunately, none of the more complex alkaloids was isolated by either procedure on this occasion.
We thank Professor D. M. James, University of Ibadan, and her collaborators for collecting and iden- tifying the plant material. Operating and Scholarship support from the National Research Council of Canada and a Province of Ontario Graduate Fellowship are gratefully acknowledged.
I . E. FUJITA, T. FLJITA, and T. SUZUKI. Chem. Pharm. Bull. 15, 1682 (1967); L. A. SILVA, L. N. PRISTA, and A. C. ALVES. Garc~a de Orta, 11, 89 (1963); F. E. K r h ~ and L. JURD. J. Chem. Soc. 1192 (1953).
2. A. B. RAY and A. CHATTERJEE. Tetrahedron Lett. 2763 (1968); H. R. ARTHUR, S. R. JOHUS, J . A. LA\%BERTON, and S. N. Loo. Aust. J. Chem. 20. 2505 (1967).
3. H. ACHEXBACH and K. BIEMANK. J. Amer. Chern. Soc. 87, 4177 (1965); L. D. ANTOXACCIO and H. BUDZ~KIEWICZ. Monatsh. Chem. 93, 962 (1962).
4. H. R. SNYDER, H. G. WALKER, and F. X. WERBER. J. Amer. Chem. Soc. 71, 527 (1949); H. R. SNYDER, C. H. HAXSCH, L. KATZ, S. M. PARMERTER, and E. C. SPAETH. J. Amer. Chem. Soc. 70, 219 (1948).
5. A. SZAKOLCAI. Unpublished results from this labora- torv.
6. N.'K. HART, S. R . JOHNS, and J. A. LAMBERTON. Aust. J. Chem. 21, 1321 (1968). W. A. AYER and T. E. HABGOOD. The alkaloids. Vol. XI. Edited by R. H . F . MAYSKE. Academic Press, New York, 1968. Chap. $0
Reaction of trialkylboranes with diazoacetaldehyde. A new synthesis of aldehydes
JOHN HOOZ AND GEOFFREY F. MORRISON Department of Chemistry, Uniuersity of Alberta, Edmontorz. Alberta
Received December 12, 1969
A new aldehyde synthesis has been developed, based on the reaction of organoboranes with diazoacetaldehyde.
Canadian Journal of Chemistry, 48, 868 (1970)
Previous publications have described syntheses ized and homologated. We have expanded this of ketones (I), nitriles (2), esters (2), and diketones versatile method to include a new, mild aldehyde (3), in which olefins, via their organoborane synthesis which permits a 2-carbon-atom exten- derivatives, have been simultaneously functional- sion (ethanaiation) of olefins by the reaction of
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