Synthesis and amphiphilic properties of glycosyl-1,4-benzodiazepin-2,5-diones

Glycosyl-l,4-benzodiazepin-2,5-diones were prepared by coupling polyhydroxy lated groups at N-1 of the corresponding benzodiazepine. The groups include 1-deoxy-D,L-xylit-1-yl, 6-deoxy-D-glucopyranos-6-yl, and 6-deoxy-3-O-R-D-g lucopyranos-6-yl (R = n-CnH2n+1 n = 8, 12, and 16). The structural variatio ns of the sugar group allowed comparison of such amphiphilic data as water solubility (Sw), critical micelle concentration (CMC), and corresponding su rface tension (gamma) values. At 25 degrees C, unsubstituted benzodiazepine s have Sw values from 0.9 to 4.2 10(-3) mol L-1, whereas xylit-1-yl and 6-d eoxy-D-glucopyranos-6-yl derivatives are, respectively, 7.4-25 and 58-204 t imes more soluble. Also, compounds with R = n-C8H17 are more soluble than c orresponding benzodiazepines (1.4-5.8 times) and give micelles with CMC fro m 2.7 to 5.6 10-3 mol L-1 and corresponding gamma from 29 to 37 mN m(-1). I n contrast, compounds with R = n-C12H25 and n-C16H33 are not soluble enough to reach the critical micelle concentration. (C) 2000 Elsevier Science Ltd . All rights reserved.