The Yohimbane Group

Several new alkaloids of this group have been recently described (see Table I, Part 1). Venenatine, isovenenatine (5, 6), and venoxidine (venenatine-Ai,-oxide) (7) from Alstonia venenata as well as oxygambir- 

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A great deal of endeavor has been spent lately in the elaboration of new synthetic approaches to the yohimbane group of alkaloids, some interesting syntheses having been reported. 

Several groups of workers have reported briefly on new or modified syntheses of the yohimbane ring system.59 The last of these communications59e describes syntheses of 14-isogambirtannine and related compounds. 

The methoxyl group was placed at C-ll (yohimban numbering) by analogy with harmine, but C-10 could not be excluded with certainty. However, it has since been shown that the spectrum of alstoniline chloride is similar to that of synthetic 3-(6-methoxy-3-methyl-2-indolyl)-2-methylisoquinolinium iodide (XXII), whereas the spectrum... 

Autrey and Scullard used this fragmentation in a synthesis of corynantheine (11) from yohimban-l7-one (7). The synthesis also involved a novel desulfurization of the enol thioether (9) without reduction of the vinyl group. This step... 

In this section are described the syntheses of some simple indolo-[2,3-a]quinolizine derivatives which bear a close relationship to the alkaloids of the yohimbane and corynane groups. 

The route employed to prepare indanone 51 involved the cycloaddition-hydrolysis-aldol sequence shown in Scheme 3.9. Accordingly, condensation of cyclopentenone 52 with ynamine 53 (84) afforded the bicyclic enamine 54 which was converted to indanones 51 and 55 by hydrolytic cyclobutane ring opening followed by intramolecular aldol condensation. Interestingly, treatment of 54 with aqueous formic acid yielded indanone 51 which has stereochemistry complementary to that at C(15) and C(20) in reserpine. In contrast, hydrolysis of this substance with aqueous hydrochloric acid afforded the trans-fused indanone 55. Subsequent to this work, the Ficini group found that esterification of 51 followed by photochemically induced addition of methanol afforded adduct 56 which has four of the reserpine stereocenters in place (23). While no further work on this problem has been reported, these preliminary investigations demonstrate a novel use of [2 -h 2] photocycloaddition chemistry in potential approaches to yohimbane alkaloid synthesis. 

The carbomethoxy group of 387 was removed to give in poor yield the yohimbane 389 which had previously been converted to yohimbol (390) by Okamura and Yamada (114). 

Monoterpene Bases.—Yohimbine-Corynantheine (and Related Oxindoles)-Pier aline Group. It is well known that 3,4-dehydroyohimbane (35a) is reduced by zinc-acetic acid to a mixture of yohimbane (35c) and i/ -yohimbane (35d) however, when 10-methoxy-3,4-dehydroyohimbane (35b) was similarly treated, a 2,3,4,7-tetrahydro-derivative (17 % yield) was formed as well as the corresponding 10-methoxy-yohimbanes. It was shown that this did not arise by further reduction of either of the methoxy-yohimbanes and no explanation is yet available for this interesting difference. Reserpine, a 6-methoxyindole, underwent C(3)-N(4) bond fission on reaction with zinc-acetic acid, as did indoles with no ring A methoxy-group. Cleavage of the C(3)-N(4) bond with the formation of N(4)-cyano-C(3)-alkoxy- or hydroxy-seco-derivatives was observed when yohimbine, i/ -yohimbine, and methyl reserpate were subjected to von Braun degradation conditions in alcohol or aqueous solution. 

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