Aspidospermine group derivatives

The three alkaloids named in the title (XXXII, XXXIII, and XXXIV) are respectively the A -formyl, -acetyl, and -propionyl derivatives of aspidospermidine (Section II, E). Demethoxypalosine (XXXIV) has been isolated from Aspidosperma limae (40) and A. discolor (40a) and was characterized as an iVa-acyldihydroindole by its UV-spectrum (Table III) and IR-absorption at 5.89 p. A strong band in the IR-spectrum at 13.1 p indicated an unsubstituted benzene ring. The foregoing information was confirmed and the substance was shown to belong to the aspidospermine group by NMR- and mass spectrometry. In the NMR-spectrum (Table IV) the 17-proton absorption is found at 8.13 well downfield from the three-proton multiplet due to the other aromatic protons which is centered at 7.07 8. This shift is due to the proximity of the carbonyl group of the iVa-propionyl group. In the aliphatic part of the spectrum, absorptions which are characteristic of the... 

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. 

Conclusive evidence that the aliphatic portion of the pyrifolidine molecule was in fact identical with that of aspidospermine (II) was obtained from the mass spectra of their deacetyl derivatives (XLVII and VI, Table V). These proved to be identical, save only in the shift of 30 units observed in the peaks attributable to fragments containing the aromatic nucleus, this shift being due to the extra aromatic methoxyl group. 

The structure of ervinidine was determined as 68 on the basis of the above information and the rationale that follows. The two carbonyls of the lactam and the ketone were placed adjacent to each other in order to account for the facile loss of 28 mu, as shown in Scheme 1, and from the same intermediate the important fragment at m/e 168 is produced. An alternative initial fragmentation (Scheme 1) leads to the ions at 228, 214, and 154 mu. Lithium aluminum hydride afforded the aspidospermine derivative 69 by cyclization. One of the problems associated with this particular structure is the possibility that it would not exist as described but rather as the 3-acylindole derivative 70. In this event, the carbonyl at 1720 cm-1 would be assigned to the ester group and that at 1690 cm-1 to the 3-acylindole function. The C-20 stereochemistry was not determined. 

From the [a]D and ORD of these alkaloids it was concluded that they all belonged in absolute stereochemical series of (—)-aspidospermine (137). The stereochemistry of the 19-hydroxy group was determined by examining the rotatory dispersion of the methylxanthate derivative of 135, which indicated the -stereochemistry for this center, as shown (62). 

---