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

Abstract 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-trifluoroacetamido-β- ( 4 ) and 2-tetrachlorophthalimido-α,β- 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 [(25 R )-spirost-5-en-3β-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-β- d -glucopyranoside hydrochloride ( 11 ) and N -acylamido derivatives. The structures of all new glycosides were established by 1 H and 13 C 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.