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

Glycosyl-1,4-benzodiazepin-2,5-diones were prepared by coupling polyhydroxylated 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-glucopyranos-6-yl (R=n-CnH2n+1; n=8, 12, and 16). The structural variations of the sugar group allowed comparison of such amphiphilic data as water solubility (Sw), critical micelle concentration (CMC), and corresponding surface tension (γ) values. At 25 °C, unsubstituted benzodiazepines have Sw values from 0.9 to 4.2 10−3 mol L−1, whereas xylit-1-yl and 6-deoxy-d-glucopyranos-6-yl derivatives are, respectively, 7.4–25 and 58–204 times more soluble. Also, compounds with R=n-C8H17 are more soluble than corresponding benzodiazepines (1.4–5.8 times) and give micelles with CMC from 2.7 to 5.6 10−3 mol L−1 and corresponding γ from 29 to 37 mN m−1. In contrast, compounds with R=n-C12H25 and n-C16H33 are not soluble enough to reach the critical micelle concentration.