Preparation and characterization of phospholanes and phospha sugars as novel anti-cancer agents

Abstract

Diastereo isomeric erythro and threo forms of 2, 3-epoxy-l- phenylphospholane 1-oxides were synthesized from threo and erythro forms of 2-bromo-3-hydroxy-l-phenylphospholane 1-oxides being prepared from l-phenyl-2-phospholene 1-oxide. Alternatively, the epoxides were also prepared by the epoxidation of the 2-phospholene with peroxides such as sodium peroxide and hydrogen peroxide. The reactivity and regioselectivity for the reaction of erythro and threo forms of the 2, 3-epoxides with nucleophiles were investigated by using amines, and the reaction afforded 2-amino-3-hydroxy-l- phenylphospholane 1-oxides, which correspond to phospha sugar N-glycosides. 2, 3-Dibromo-3-methyl-l-phenylphospholane 1-oxides were first prepared from 3 -methyl-1-phenyl-2-phospholene 1-oxide. The prepared phospholanes or phospha sugars werebiologically qualified by MTT (3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyltetrazolium bromide) in vitro method to find that some of these phosphorus heterocycles or phospha sugars have quite efficient anti-cancer activity for leukemia cells in manners of (i) wide spectra, (ii) high activities, and (iii) high specificities.