Enantioselective synthesis of indolizidine alkaloids: formal synthesis of (–)-swainsonine and of (+)-pumiliotoxin 251D

Abstract

Oxidative treatment of optically active 2-furylmethanol (furfuryl alcohol) derivative (R)-5, obtained by Sharpless kinetic resolution of the racemate, afforded the pyranone 9, which on successive reduction with lithium aluminium hydride in the presence of copper(I) iodide and with sodium boranuide (NaBH₄), followed by conversion into imidazolide 14, was subjected to a radical cyclization reaction to provide the bicyclic compound 15, stereoselectively. The cyclopentanone oxime (E)-25, derived from the ketone 23, was subjected to Beckmann rearrangement to afford lactam 26, which was further cyclized to give the indolizidine 30, an intermediate for (+)pumiliotoxin 251 D 31. Whereas dihydroxylation of lactol 32 gave triol 34, which after protection as acetonide 35 was also converted into imidazolide 37. Radical cyclization of compound 37 produced the bicyclic compound 38, stereoselectively, whose Lemieux–Johnson oxidation followed by Birch reduction gave alcohol 40. The cyclopentanone 45 was further formally transformed into swainsonine 1 by a similar synthetic route to that above.