Strategic approaches to the synthesis of pyrrolizidine and indolizidine alkaloids

Abstract

The principal methods for the synthesis of pyrrolizidine and indolizidine alkaloids and their unnatural analogs are described. Six main “strategic” approaches in regard to a key step forming azabicyclic skeleton are identified. Namely, these are: 1) hydrogenation of the corresponding heteroaromatic compounds; 2) various condensations of carbonyl compounds and their surrogates; 3) cycloaddition reactions; 4) sigmatropic shifts and other rearrangements; 5) transition metal-mediated cyclizations (including the ring-closing alkene metathesis); and 6) radical processes. Such important issues, as retrosynthetic analysis, chiral pool synthesis, and chiral auxiliaries, are also discussed.