Modifications of lincomycin involving the carbohydrate portion. Part I. The 2-O-methyl and 2-deoxy-analogues

Abstract

2-O-Methyl-lincomycin has been synthesised via the O-methylation of either methyl N-acetyl-3,4-O-isopropylid-ene-1-thiolincosaminide or its 6-deamino-7-deoxy-2′-methyl-[6,7-d]-Δ^2′-oxazoline derivative, obtained from methyl thiolincosaminide, the carbohydrate portion of the antibiotic lincomycin. The glycal obtained by treatment of either of the anomeric N-acetyl-2,3,4,7-tetra-O-acetyl-lincosaminyl bromides with zinc, reacts normally with hydrogen bromide to give the anomeric N-acetyl-3,4,7-tri-O-acetyl-2-deoxylincosaminyl bromides, thereby providing a route to 2-deoxy-α- and β-lincomycins. The effect of the structural modifications in these analogues on antibacterial activity is discussed.