A Facile Synthesis of ¹⁴C Labeled Novel Anti-PAF Active Thiazolidin-4-one

Abstract

(2R, 5S) - (+) -cis-3, 5-Dimethyl-2- (3-pyridyl) thiazolidin-4-one hydrochloride (SM 12502), a new PAF antagonist, was labeled with carbon-14 at C 2 of the thiazolidinone ring for use in metabolic studies. The synthesis was achieved according to the scheme illustrated in Fig, 3. ¹⁴C-Carbonation of 3-pyridyllithium (3) followed by chlorination and esterification gave mehyl [carbonyl-¹⁴C] nicotinate (6) . Reduction of 6 with diisobutylaluminium hydride produced a mixture of the alcohol (7) and the aldehyde (8) . Oxidation of the mixture with manganese dioxide gave 8 as a sole product. Condensation of 8 with methylamine and subsequent cyclocondensation of the imine (9) with (S) -2-mercaptopropionic acid (10) yielded a cis and trans mixture of the thiazolidinone (11) . Isolation of the desired stereoisomer by chiralphase HPLC and subsequent treatment with hydrochloric acid afforded 1. The overall yield of 1 was 22% from 2.