Diastereoselective Synthesis of Lincosamine Precursors

The stereoselective syntheses of the four aminodiol precursors of the diastereomers of lincosamine are reported. The procedure is based on the initial two-carbon elongation of 1,2;3,4-di-O-isopropylidene-α-D-galactohexodialdo-1,5-pyranose, followed by the stereocontrolled introduction of the amino group by nucleophilic amination. Two complementary approaches have been investigated and compared: The first one is the direct transformation of α-chloroglycidic ester into β-amino-α-keto ester. The second strategy is a three-step synthesis that is based on the treatment of the β-iodo-α-keto ester with dibenzylamine. Subsequent reduction of the β-amino-α-keto ester provides the pure D-erythro, L -threo, L-erythro, and D-threo aminodiols after chromatographic purification. Further classical transformations afford the N-acetyl derivatives, which are key precursors of the lincosamine diastereomers.