From Sugar Lactones to Stereodefined γ-Alkylidenebutenolides – Synthesis of Analogs of the γ-Alkylidenebutenolide Antibiotics Lissoclinolide and Tetrenolin

Abstract

A novel strategy for the stereoselective synthesis of E- or Z-configured γ-alkylidenebutenolides was applied to the preparation of the model compounds 6/7 (E) and 8/9 (Z) of the antibiotics tetrenolin (E) and lissoclinolide (Z), respectively. For introducing the α-substituents of the target molecules the butenolide triflates ul- and lk-16 were subjected to Stille couplings with trans-Bu3Sn–CHCH–CH2–OH or trans,trans-Bu3Sn–CHCH–CHCH–CH2–OH (room temp., 10 min). Acetonide cleavages and bis(tert-butyldimethylsilylations) set the stage for introducing the CexocyclicCγ bonds through anti-selective (ds = 96:4-99:1) eliminations of triflic acid (ul-21→E-23, lk-21→Z-23, ul-22→E-24, lk-22→Z-24).