合成路线1

Palladium-catalyzed coupling between (S)-4-ethynyl-2,2-dimethyl[1,3]dioxolane (I) and ethyl 5-bromothiophene-2-carboxylate (II) afforded the acetylene adduct (III), which was further hydrogenated to (IV) in the presence of Pd/C. Acid hydrolysis of the acetonide function of (IV) gave diol (V). In order to invert the configuration of the chiral center of (V), its primary hydroxyl group was protected as the silyl ether (VI) and the secondary alcohol was subsequently converted to mesylate (VII). After desilylation of (VII) by means of tetrabutylammonium fluoride, the resultant mesylate alcohol was cyclized to epoxide (VIII) upon treatment with NaH in THF. Epoxide ring opening in (VIII) with NaN3 furnished azido alcohol (IX). Then, azide reduction in the presence of Boc2O gave rise to the Boc-protected amine (X). Introduction of a sulfur atom was accomplished by conversion of alcohol (X) to mesylate (XI), followed by displacement with potassium thioacetate to yield (XII). Concomitant thioacetate ester (XII) hydrolysis and alkylation of the intermediate thiol with chloromalonate (XIII) provided the mercaptomalonate (XIV).