Asymmetric formal total synthesis of (–)-swainsonine

Abstract

A new concise noncarbohydrate-based enantioselective approach to (–)-swainsonine 1 is described, utilizing the kinetic resolution of α-furfuryl amide 4 and the Sharpless AD reaction of 9a as key steps. Kinetic resolution of α-furfuryl amide 4 using the modified Sharpless asymmetric epoxidation reagent with D-(–)-DIPT as the chiral ligand, gave the chiral building block the dihydropyridone 5. Reduction of the α,β-unsaturated ketone 6a with sodium boranuide gave the 3β-OH product 7. Dihydroxylation of 9a, with Sharpless AD reagent using DHQ-CLB as the chiral ligand, provided the 1,2-glycols 10a and 10b in ratio of 10 : 1. Detosylation of the triol 11 afforded the amino alcohol, which underwent intramolecular cyclization by treatment with CC1₄–PPh₃–Et₃N giving (–)-8-benzyloxy-swainsonine 12. Compound 12 was converted into the acetonide 13, which underwent subsequent formal deprotections to afford (–)-swainsonine 1.