Aldol reactions of ketal-protected tartrate ester enolates. Asymmetric syntheses and absolute stereochemical assignments of phospholipase A(2) inhibitors cinatrin C-1 and C-3

An efficient approach to the syntheses of cinatrins C-1 and C-3 has been developed and used to establish the absolute configurations of these natural products. The construction of each molecule has been achieved in a five-step reaction sequence (overall yield 43% for cinatrin C-1, 33% for cinatrin C-3) from the di-tert-butyl ester of (R,R)-tartaric acid. The two contiguous, quaternary chiral centers in the cinatrin skeleton are constructed via a diastereoselective, titanium-mediated aldol coupling of a tartrate-derived silylketene acetal and an achiral alpha-ketoester. This bond construction proceeds with excellent diastereoselectivity for a variety of aldehyde and alpha-ketoester substrates. (C) 1997 Elsevier Science Ltd.