Enantiospecific synthesis of the phospholipase A2 inhibitors (-)-cinatrin C1 and (+)-cinatrin C3

The enantiospecific synthesis of (-)-cinatrin C-1 (3) and (+)-cinatrin C-3 (5) from the D-arabinose derivative 9 is described. The stereochemistry at C2 was introduced via a chelation-controlled addition of a carbanion to alpha-hydroxy ketone 8. The best selectivity was achieved by use of the Grignard reagent derived from trim ethylsilylacetylene. Transformation of the terminal alkyne into methyl ester 17 followed by acetal hydrolysis and selective lactol oxidation gave cinatrin C-1 dimethyl ester (7). Base hydrolysis and acid induced relactonization then gave a 1 : 1 mixture of cinatrins C-1 (3) and C-3 (5).