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 elongationof 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.