The synthesis and biological activities of some analogs of streptozotocin.

The aand /?-methyl glycosides (IV and V, respectively) of the antibiotic streptozotocin (I) have been synthesized. In addition, analogs involving epimeric changes at C2 (III) and C4 (II), and of two Q analogs, 3-/?-Dglucopyranosyl-1-methyl-l-nitrosourea (XXIII) and the corresponding Dgalactopyranosyl compound (XXV), together with their tetra-O-acetates (XXII and XXIV, respectively) have been prepared. An open-chain analog was obtained by the synthesis of l-deoxy-l-(3-methyl-3-nitrosoureido)-D-glucitol (XXIX), but the 2-deoxy-D-glucitol derivative (XXVII) decomposed on attempted isolation. Epimerization at C2 reduces the antibacterial activity markedly; all other changes made destroy it. All of the analogs show cytotoxic activity in the range of streptozotocin or higher, and all are devoid of diabetogenicity.