Stereocontrolled lincomycin synthesis

Article abstract of DOI:10.1021/jo00292a044

The synthesis from methyl α-D-galactopyranoside (6) of methyl thiolincosaminide (2), the direct synthetic precursor to lincomycin (1), is presented. The key step for controlling the off-pyranose stereocenters C-6 and C-7 is a novel intramolecular nitrogen delivery reaction using epoxy alcohol 10. Reaction of 10 with dimethylcyanamide in the presence of sodium hydride and imidazole leads to the oxazoline 14, a protected vicinal amino alcohol. The synthesis is completed by efficient exchange of acetal for thioacetal, followed by hydrolysis of the oxazoline and removal of the benzyl groups. The target 2 is obtained in 22 steps and 28% overall yield from 6.