SE-77 NMR AND CRYSTALLOGRAPHIC STUDIES OF SELENAZOFURIN AND ITS 5-AMINO DERIVATIVE

Studies presented here examine the hypothesis that the close Se-Ol' contact observed in the chemotherapeutic agent selenazofurin is electrostatic in origin. The crystal structure and 77Se spectrum of selenazofurin are compared with those of the 5-amino derivative. The 77Se spectrum of selenazofurin shows a doublet of doublets at 774.2 (5) ppm downfield of dimethyl selenide. A two-bond J coupling of 44.3 Hz is observed between Se and the selenazole heterocycle proton H5. A three-bond J coupling of 3.2 Hz is observed between Se and the furanose proton H1'. These observations are consistent with a positively charged selenium in a partially delocalized selenazole ring, in agreement with earlier X-ray studies. The 77Se signal for the 5-amino derivative appears as a doublet at 687.5 (5) ppm relative to dimethyl selenide and 87 ppm upfield from that observed for the parent compound. A two-bond J coupling between Se and H1' of 4.2 Hz is observed in the 5-amino derivative. The crystal structure of 5-aminoselenazofurin shows an unusually high glycosidic torsion angle with an increase in the Se-Ol' distance relative to that found in the parent compound. These findings are consistent with a decrease in positive charge on the selenium in the 5-amino derivative, resulting in a decrease in the attractive component of the Se-Ol  interaction and a shift in conformation about the C-glycosidic bond. © 1990, American Chemical Society. All rights reserved.