Synthesis and induction of apoptosis in B cell chronic leukemia by diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride and its derivatives

2-Acetamido-2-deoxy-D-glucose hydrochloride (D-glucosamine hydrochloride) has been used for the preparation of 1,3.4.6-tetra- O-acetyl-2-deoxy-2-trifluoroacetqamido-beta- (4) and 2-tetrachlorophthalimido-alpha, beta-D-glucopyranose (6) which have been transformed into the appropriate bromides and the chloride. Both bromo and chloro sugars were used as a glycosyl donors for the glycosylation of diosgenin [(25R)-spirost-5-en-3beta-ol]. These condensations were conducted under mild conditions, using silver triflate as a promoter, and gave diosgenyl glycosides 9 and 12. Each of them was converted into diosgenyl 2-amino-2-deoxy-beta-D-glucopyranoside hydrochloride (11) and N-acylamido derivatives. The structures of all new glycosides were established by H-1 and C-13 NMR spectroscopy. These diosgenyl glycosides are the first saponins containing the D-glucosamine residue that have been synthesized. These compounds show promising antitumor activities, The synthetic saponins increase the number of apoptotic B cells, in combination with cladribine (2-CdA). that are isolated from chronic lymphotic leukemia (B-CLL) patients. (C) 2002 Published by Elsevier Science Lid.