Asymmetric dithioacetals III: The preparation of the enantiomers of 3-((((3-(2-(7-chloroquinolin-2-YL)-(E)-ethenyl)phenyl)-3-dimethylamino-3-oxopropylthio)methyl)thio)propionic acid (l-660,711) (mk-571), an antagonist of leukotriene D4

The application of a novel method for the preparation of chiral dithioacetals to the synthesis of the enantiomers of L-660,711, an antagonist of leukotriene D4, is described. Reaction of 3-(t-butyld1phenylsilyloxymethyl)benzaldehyde or isophthalaldehyde with (R)-(-)-α-methoxyphenylthiolacetic acid and N,N-dimethyl-3-mercaptopropionamide provides diastereomeric acylthioalkylthioacetals (10,11 or 17a,b) which are readily separable and can be subsequently deacylated with sodium methoxide and the resultant thiolate anion alkylated with methyl acrylate to provide enantiomeric dithioacetals (12a,b or 14a,b) which are converted to the enantiomers of L-660,711. © 1989.

Duke Scholars

Author Michael J. Therien Chemistry