EFFICIENT TOTAL SYNTHESIS OF 1R,2R,3R,9R,9AR)-1,2,3,9-TETRAHYDROXYQUINOLIZIDINE AND ITS ENANTIOMER

Concise syntheses of two enantiomeric tetrahydroxyquinolizidines, 10 a nd ent-10, have been achieved from D-arabinose and L-arabinose, respec tively. Highly diastereoselective homologation of imine 5 (or ent-5) u sing 2-(trimethylsiloxy)furan provided the nine-carbon butenolide 6 (o r ent-6) which was elaborated into the quinolizidine 10 (or ent-10) vi a a clean sequence involving, as key operations, DBU-promoted gamma-la ctone to delta-lactam ring expansion (e.g. 7 to 8) and cyclodehydratio n of a fully-deprotected hydroxypiperidine employing Ph3P, CCl4, Et3N (e.g. 9 to 10). The procedure comprises five steps from 5 or ent-5 and provides the title quinolizidine 10 or its enantiomer ent-10 in 36-37 % overall yields.