The Aspidofractinine Group

In the case of the aspidospermine group (Section II), the nature of the carbon skeleton was elucidated for aspidospermine only, the structures of the other members of the group following by correlation with this alkaloid, either directly or mass spectrometrically. Although mass spectrometry alone suggested the structure CXVII for the skeleton of some Aspidosperma alkaloids, the final proof of CXVII rests on both 

In many spectra of alkaloids of this group, the indolic peaks are small as compared with the aspidospermine-type molecules. In some cases they stand out, however, and peaks corresponding to fragments m and n occur in the spectra of O-methyldeacctylaspidofiline (CXXXIX) and deformyl-refractidine (CXXII), while the lactams, pleiocarpinilam (CXLVI-D) and pleiocarpine lactam A (CXLV-D), exhibit intense peaks due to the fragments l and p (102). 

On the basis of the foregoing information, it has been possible to determine the complete structures of alkaloids in this group by use of reactions designed only to modify superficial substituents (80, 81, 82, 95). Other possible skeletal structures which might be compatible with the observed spectra are excluded by chemical evidence described subsequently. 

This is shown by the IR-absorption of the three lactams, pleiocarpine lactam A (CXLV-D), pleiocarpinilam (CXLVI-D), and kopsinilam (CXLII-D Section III, H), which is compatible only with their being y-lactams [compare, for example, 8- and 10-oxoaspidospermine (XX, XI), Section II, C], 

The carbon atom, C-3, which in the kopsinine subgroup bears a carbo-methoxyl substituent, has been shown by the mass spectral evidence summarized above not to be in the six-membered ring which contains Nb. That it lies in a strained six-membered ring is indicated by degradation of the carbomethoxyl groups of refractine (CL-A) and aspidofractine (CXLIII-A) to C-3 ketones (CXLIX-P and CXLII-P), whose IR-absorption occurs at unusually low wavelengths (5.76-5.78 p) (Section III, G). 

Aspidofractinine (146), the parent member of this third large subgroup of alkaloids of the aspidospermine group, does not occur widely, and the only recent report of its occurrence is in the stem bark and root bark of Hunteria elliottii Pichon (12). Its Na-methyl (147) and Na-methyl-14,15-didehydro (148) derivatives are new alkaloids, which have been found in the roots of Vinca sardoa (67). The ester alkaloids occur much more widely, and several new sources have been reported for (—)-kopsinine (149), (-)-venalstonine (150), (-)-venalstonidine (151), and several minor alkaloids (152-160) (Table I). Of the six reported isolations of 15a-hydroxykopsinine (154), one (16) does not spedfy the configuration of the hydroxyl group. Since it is described as a known alkaloid, it is presumed to be 15a-hydroxykopsinine, because 15/3-hydroxykopsinine is unknown as a natural product. 

The structure of kopsamine (158), previously unknown, has been revealed by X-ray crystallography (165). 

15-Didehydro-17a-hydroxykopsinine (162) is one of several new bases from Kopsia teoi (84,163,164). Its presumed 16-epimer 163 was later isolated from the stem bark of the same plant, but the relationship between the 

1 Hz in the alkaloid isolated by Varea et al. (8J) and formulated as 163. In other respects the spectra of these two alkaloids appear to be identical hence, their identity as two distinct epimers remains to be firmly established. 

The new alkaloids of Kopsia deverrei L. Allorge, a large Malaysian tree, are (+)-kopsinone (165) (167) and its 10-methoxy- (166) and 12-methoxy-(167) derivatives, 14,15-dihydro-lO-methoxykopsinone (168) (168), (-)-17)8-hydroxy-A a-niethoxycarbonylkopsinine (169), and its 14,15-didehydro derivative 170 (767). 

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Ten alkaloids have been isolated from A. populifolium, of which the greater part belong to the aspidofractinine group (48). They include (+ )-0-methyldeacetylaspidofiline [CXXXIX, optical enantiomer of that derived from aspidofiline (Section III, E)], its 16-methoxy analog, CXLI-A, and their respective A7a-formyl derivatives, CXLI-B and CXLI-C. The structures of all four compounds could be established by comparison of their IR-, UV-, NMR-, and especially mass spectra with... 

Although the alkaloids of Aspidosperma populifolium are preponderantly of the aspidofractinine type, one of them (CCXXIV-A) was clearly excluded from this class by its IR- (ACHCl3 5.98 and 6.25 p, MeC C—C=C) and UV- (Table III) spectra. The latter was somewhat similar to that of condylocarpine (CCXV), the differences being accountable to an aromatic methoxyl group whose presence was indicated by the NMR-spectrum (OCH3, 3.74 S, coincident with the CC Me peak 3 aromatic protons only). A further difference from condylocarpine and akuammicine lay in the presence of an ethyl (0.70 S, triplet) rather than ethylidene side chain. 

The electrochemical oxidation of the aspidofractinine-type alkaloid kopsingine in a dichloromethane/acetonitrile medium at a platinum anode in the presence of 2,6-lutidine results in the intramolecular cyclization of an hydroxy group to the intermediate iminium ion of the tertiary amine structure. Thus, kopsidine A was formed in 72% yield [19]. 

Eburnamine-Aspidospermine-Aspidofractinine Group. An A-ray analysis48 of obscurinervine hydrobromide has confirmed the structure arrived at earlier by chemical and spectroscopic means. 

Several new derivatives of kopsingine or kopsaporine with different aromatic substitution which were recently obtained include 11-hydroxykopsingine (193) [131], 11-methoxy-kopsingine (194) [131] and 11,12-methylenedioxykopsaporine (195) [132]. Another new aspidofractinine, kopsinol (196) [130] was readily shown to be the N(l)-decarbomelhoxy derivative of kopsaporine while compound 197 was assigned the structure 11-methoxy-12-hydroxykopsinol from the spectral data [131]. The position of the aromatic methoxy group in 197 was established to be at C(l I) from the observed NOE between H(10) and the aromatic OMe. 

Two new aspidofractinine compounds M arbomethoxy-l7P-hydroxykopsinine (205) and -carbomethoxy-17 i-hydroxy-A -kopsinine (206) were obtained from K. deverrei and are characterized by the absence of the C(16) hydroxyl group when compared with kopsaporine. The assignments of the stereochemistry of the C(16) methyl ester and C(I7) hydroxyl substituents as P were based on the absence of W-coupling between H(I6) and H(I7) to any of the C( 18) and C(I9) hydrogens respectively. 

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