Synthesis and sequential diastereoselective incorporation of hydroxyl groups into hexahydrofuro[3,2-f]indolizin-7(2H)-one to give mono-, di- and tetra-hydroxyfuroindolizidines.

Abstract

Dihydrofuro[2,3-f]indolizidinone obtained from biosourced reagents even at multigram-scale was used as an advanced building-block with up to five points of chemical diversification. This resulted in the sequential synthesis of a series of mono-, di- and tetra-hydroxyfuranoindolizidines belonging to a very scarce and elaborate tetrahydrofuran-fused indolizidine family with up to six controlled stereogenic centers. These sequences include, among others, diastereoselective olefin epoxidation, stereoselective epoxide ring opening into tetrahydrofuran trans-diols, their protection as an ester or acetonide, and lactam carbonyl reduction ultimately followed by acetate or acetonide deprotection.