Quinolizidines. XVIII. Syntheses of (-)- and (+)-ankorines through a lactim ether route.

Abstract

A formal chiral synthesis of the Alangium alkaloid (-)-ankorine [(-)-6] has been accomplished in the form of the synthesis of the lactam phenol (+)-14 from the (+)-trans-lactim ether (+)-5 and 2-benzyloxy-3, 4-dimethoxyphenacyl bromide through the intermediates (+)-10 and 11. A parallel sequence of conversions starting from the (-)-trans-lactim ether (-)-5 and proceeding through the intermediates (-)-10, 24, (-)-14, (-)-15, 26, (+)-27, and (+)-28 produced the enantiomer [(+)-6] of natural ankorine. For an alternative chial synthesis of (-)-6, ethyl cincholoiponate [(+)-19] was acetylated and the resulting N-acetyl derivative (+)-20-was oxidized with RuO4 to give the 6-piperidone (+)-21, and 2-piperidone (-)-23 in 55% and 27% yields, respectively. The (-)-cis-lactim ether (-)-16, obtained by ethylation of (+)-21 with triethyl-oxonium fluoroborate, was then converted into (-)-13, a known precursor for the synthesis of (-)-ankorine [(-)-6], in good overall yield by a lactim ether route, which proceeded through (+)-15 and 12.