SYNTHESIS OF (-)-TALAUMIDIN, A NEUROTROPHIC 2,5-BIARYL- 3,4-DIMETHYLTETRAHYDROFURAN LIGANAN, AND ITS STEREOISOMERS

摘要

The enantioselective total synthesis of a neurotrophic (-)-talaumidin (1) was achieved in 16 steps from 4-benzyloxy-3-methoxybenzaldehyde in ca. 10.7% overall yield. The synthesis features the construction of the two successive chiral centers C-2 and C-3 by Evans asymmetric anti-aldol protocol as well as of the two chiral centers C-4 and C-5 in a highly stereocontrolled fashion by hydroboration/oxidation and epimerization, followed by Friedel-Crafts arylation. Its stereoisomers (2S,3S,4S,5R)-1a and (2S,3S,4R,5S)-1b were also synthesized from a key intermediate 10 with the 2S and 3S configurations.