A convergent approach toward phoslactomycins and leustroducsins

Synthetic studies devoted to the development of a convergent approach toward phoslactomycins and leustroducsins, a family of natural products inhibitors of serine/threonine phosphatase 2A, are reported. A formal synthesis of phoslactomycin B was achieved in which the key steps are a [2,3]-Wittig rearrangement to control the C4 and C5 stereocenters, a diastereoselective addition of an acetylenic Grignard reagent to an alpha-alkoxy ketone to create the C8 tertiary alcohol, and a relay ring-closing metathesis to construct the alpha,beta-unsaturated delta-lactone. In this approach, all the stereocenters originate, either directly or indirectly, from catalytic enantioselective reductions of acetylenic ketones. (C) 2010 Elsevier Ltd. All rights reserved.