General methods for modification of sialic acid at C-9. Synthesis of N-acetyl-9-deoxy-9-fluoroneuraminic acid

Abstract

Methyl 5-acetamido-3,5-dideoxy-2- O-methyl- d- glycero- d- galacto-2-nonulopyranosate was converted into the 9- O-trityl derivative and the remaining hydroxyl groups were protected as benzyl ethers. Removal of the trityl group, followed by treatment with diethylaminosulfur trifluoride gave the 9-deoxy-9-fluoro derivative, and deprotection N-acetyl-9-deoxy-9-fluoroneuraminic acid ( 8). In another procedure, coupling of 2-acetamido-2,6-dideoxy-6-fluoro- d-glucopyranose with potassium di( tert-butyl) oxaloacetate, followed by hydrolysis and decarboxylation gave 8. Some of the derivatives were active as inhibitors of growth of mouse mammary adenocarcinoma (TA 3) and L1210 cells in culture.