Quinolizidines—V : A novel synthetic route to Ipecac alkaloids through chemical incorporation of ethyl cincholoiponate derived from the cinchona alkaloid cinchonine

A new synthetic route to (?)-emetine (1) and related Ipecac alkaloids has been exploited in terms of the synthesis of the tricyclic ester (?)-30 from ethyl cincholoiponate (+)-4], a degradation product of the Cinchona alkaloid cinchonine (7). The steps involved are those in the sequence (+)-4→(+)-8→9→10→(?)-12-→(?)-13→ (+)-21→(+)-22→28→29→(?)-30. In the Hg(OAc)₂-EDTA oxidation of the amino alcohol 9 to the 6-piperidone 10, the cis- and the trans-2-piperidone isomers 11 were the minor products. The successful conversion of the cis-lactam acid (?)-13 into the trans-lactam acid (+)-21 was effected on the basis of the fact that (±)-13 and (±)-21 are convertible to each other through cis-trans equilibration (13:21 = 33:67) at 180° in 75 min. When this isomerisation step was skipped in the above reaction sequence, the 2,3-cis-tricycle (+)-33, synthetic precursor for chiral 2,3-cis-emetines, was obtained.