A Butyrolactone → 1,3‐diol Strategy for the Obtention of Tolypothrix Polyethers – Total Synthesis of the Tolypothrix Pentaether from Enantiomerically Enriched S‐Glycidol

Abstract

AbstractPermethyl ether 1 from Tolypothrix conglutinata was synthesized following the retrosynthetic analysis of Scheme 1. According to it, we combined aldehyde 3 [prepared from S‐glycidol (7); cf. Schemes 2, 3] and lactone 4 (also prepared from S‐glycidol (7); cf. the preceding communication[2] and Scheme 4) to the enantiopure and diastereopure trimethoxy lactone 2 (Scheme 5). The CO group of this lactone was removed through the Criegee rearrangement of a derived lactol peroxonosylate (Scheme 6); thereby, the CCO bond of lactone 2 was replaced with complete retention of configuration by one COH bond of the resulting syn‐configured diol 18. Protecting group manipulations (Schemes 6, 7) and oxidation of the resulting alcohol 21 to aldehyde 31 (Scheme 10) initiated the three final operations: C2‐homologation with Ph3PCH‐CHO (→ enal 32), tosyl hydrazone formation (→ 34), and reduction/concomitant CC bond migration. They led to the target ether 1 as a 89:11 mixture with the CHCH‐richer ether 36.