On topography and functionality in the B-D rings of cephalostatin cytotoxins

Analogues 12′β-hydroxycephalostatin 1 (9), 7′-deoxyritterazine G (10), and 14-epi-7′-deoxyritterazine B (11) were prepared via our protocol for unsymmetrical pyrazine synthesis. Cytotoxicity against human tumors was also determined for the first time for ritterazines, with femtomolar potency and a high correlation to cephalostatins observed. The SAR of these and related compounds provide insight into the importance of topography and certain chemical functionality in the B-D and B′-D′ rings of cephalostatin type antineoplastics.