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 alpha-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).
Cuzzupe
Anthony N
AN
School of Chemistry, The University of Melbourne, Victoria, 3010, Australia.
Di Florio
Romina
R
White
Jonathan M
JM
Rizzacasa
Mark A
MA
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007783:Lactones; C073569:cinatrin C1; C073571:cinatrin C3; D010741:Phospholipases A; D054467:Phospholipases A2