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

The enantiospecific synthesis of (−)-cinatrin C₁ (3) and (+)-cinatrin C₃ (5) from the D-arabinose derivative 9 is described. The stereochemistry at C2 was introduced via a chelation-controlled addition of a carbanion to α-hydroxy ketone 8. The best selectivity was achieved by use of the Grignard reagent derived from trimethylsilylacetylene. Transformation of the terminal alkyne into methyl ester 17 followed by acetal hydrolysis and selective lactol oxidation gave cinatrin C₁ dimethyl ester (7). Base hydrolysis and acid induced relactonization then gave a 1 : 1 mixture of cinatrins C₁ (3) and C₃ (5).