A Simple Entry to the 5,8-Disubstituted Indolizidine Skeleton via Hetero Diels-Alder Reaction

The 5,8-disubstituted indolizidines are the largest family of indolizidines isolated from the skin of amphibians. These compounds exhibit interesting biological activities such as noncompetitive blockers of nicotinic receptors. In this paper, we present a short, simple, and general synthesis of these alkaloids based on the hetero Diels-Alder reaction between suitable monoactivated dienes and Delta(1)-pyrroline as the dienophile. The selectivity of the process is explained based on computational studies. Concise synthesis of the indolizidine alkaloid 181B from a hetero Diels-Alder reaction was accomplished in four steps.

Automated summary

A short, simple, and general synthesis of 5,8-disubstituted indolizidines, the largest family of indolizidines isolated from amphibian skin, is presented in this paper. These compounds exhibit interesting biological activities such as noncompetitive blockers of nicotinic receptors. The selectivity of the synthesis process is explained based on computational studies. The concise synthesis of indolizidine alkaloid 181B from a hetero Diels-Alder reaction was accomplished in four steps.