Catalytic Asymmetric Synthesis of a Potent Thiomarinol Antibiotic

Abstract

Thiomarinols, isolated from the bacterium Alteromonas rava sp. nov. SANK 73390, are potent marine antibiotics that possess both Gram-positive and Gram-negative activity. The first total synthesis of a member of the thiomarinol class of marine antibiotics was achieved in a remarkable global yield of 22% (from 3-boronoacrolein pinacolate). The highlight of this synthesis is the efficient catalytic enantio-, regio-, E/Z-, and diastereoselective three-component inverse electron demand Diels-Alder/allylboration sequence. This key operation provides a rare example of an enantioselective HDA reaction involving acyclic 2-substituted enol ethers, and it featured an unusual but fortuitous kinetic selection that favored the requisite Z-dienophile.