Total Synthesis of Dolabelide C: A Phosphate-Mediated Approach

• DOI: 10.1021/jo2003506
• Publication Date: 2011-04-29T14:34:43Z
• Authors: Paul R. Hanson; Rambabu Chegondi; John Nguyen; Christopher D. Th...; Joshua D. Waetzig; Alan Whitehead
• Keywords: Cyclization; Stereoisomerism; Macrolides; 540; 01 natural sciences; Catalysis; Phosphates; 0104 chemical sciences

The first synthesis of dolabelide C (1), a cytotoxic marine macrolide, is reported utilizing a phosphate tether-mediated approach. Bicyclic phosphates (S,S,S(P))-5 and (R,R,R(P))-5 serve as the central building blocks for the construction of two major 1,3-anti-diol subunits in 1 through selective cleavage pathways, regioselective olefin reduction, and cross-metathesis. Overall, phosphate-mediated processes provided copious amounts of both major subunits allowing for a detailed RCM macrocyclization study to the 24-membered macrolactone 1.