Total synthesis of indole and dihydroindole alkaloids. 14. A total synthesis of vindoline

A Review on Recent Developments in Syntheses of the Post-Secodine Indole Alkaloids. Part I: The Primary Alkaloid Types

“…The conversion of benzyloxymethyl group to a carbonyl was addressed next, which proceeded via the osmium tetroxide-mediated dihydroxylation of an exocyclic olefine. After substitution of a methyl for the highly stabilising N-mesyl group in 390, the final diol scission completed synthesis of the tetracyclic ketone 383, which constitutes a formal synthesis of the racemic alkaloid 143 …”

Alkaloids

“…Ellipticine (340) [333] and olivacine (341) [334] lack the normal tryptamine unit in their fundamental structure; however, they are placed with the Aspidosperma alkaloids as they were found in Aspidosperma species. Interest in the synthesis of these alkaloids stems from their marked antitumor activity.…”

“…The first synthesis of ellipticine (340) was achieved by Woodward [335]. Olivacine (341) was synthesized by several groups [336]. Uleine (342), apparicine (343), and vallesamine (344) also do not bear a tryptamine unit as a distinguishable feature in their fundamental structure, but they are normally grouped under the Aspidosperma family since they occur in Aspidosperma species.…”

“…Stork's first synthesis of aspidospermine (345) utilized an enamine annelation reaction and Fischer indole cyclization of a phenylhydrazone derivative [339]. The synthesis of vindoline (348), a major component of Vinca rosea, was accomplished by Büchi [340] and Kutney [341], and this alkaloid is an important compound because it is the precursor of dimeric indole alkaloids possessing antitumor activity. Treatment of vincadifformine, obtained from tabersonine (347) by partial reduction with formic acid and formamide followed by reduction, afforded vincadine and quebrachamine (346 …”

Stereocontrolled total synthesis of (+)-vincristine

“…Numerous synthetic studies have been directed toward Vinca alkaloids (7)(8)(9)(10)(11)(12)(13)(14), and to date four total syntheses of vinblastine (1) have been reported (15)(16)(17)(18). In contrast, vincristine (2), which is more difficult to obtain than vinblastine (1) because of very low content in the plant (Ϸ0.0003% yield from C. roseus),…”