SYNTHESIS OF O-METHYLSULFONYL DERIVATIVES OF D-GLUCOSE AS POTENTIAL ALKYLATING-AGENTS FOR TARGETED DRUG-DELIVERY TO THE BRAIN - EVALUATION OF THEIR INTERACTION WITH THE HUMAN ERYTHROCYTE GLUT1 HEXOSE TRANSPORTER

In order to obtain hydrophilic analogues of 1,4-dimethylsulfonyloxybut ane (busulfan) with enhanced selectivity and improved brain penetratio n, we have synthesized 6-O-methylsulfonyl-D-glucose, 3-O-methylsulfony l-D-glucose, 3,6-di-O-methylsulfonyl-D-glucose, 4-O-methylsulfonyl-D-g lucose, and 4,6-di-O-methylsulfonyl-D-glucose, and we have studied the ir interactions with the human erythrocyte GLUT1 hexose transport syst em. Mesylation of OH-4 and OH-6 of glucose resulted in a slightly dimi nished affinity for the GLUT1 glucose transporter, whereas mesylation of OH-3 led to complete loss of affinity. (C) 1997 Elsevier Science Lt d.