Divergent Synthesis of Three Classes of Aryl N-Glycosides by Solvent Control
Journal of Organic Chemistry
American Chemical Society
Aryl glycosides represent a group of molecules with immense biological applications and implications. While the syntheses of aryl C-glycosides and O-glycosides have been studied extensively, the preparation for aryl N-glycosides is relatively unexplored. By employing 1,4-naphthoquinone and glycosyl azides undergoing a [3 + 2] cycloaddition, we have developed a convenient method for constructing three different classes of aryl N-glycosides that include N-glycosylated 2-aminomethylene-1,3-indanedione, benzazepine-1,5-dione, and 9,10-anthraquinone derivatives via solvent control. It was found that conducting cycloaddition in DMF formed exclusively 9,10-anthraquinone derivatives, while less polar solvent such as toluene offered all three aryl N-glycosides. The synthesis of N-glycosylated 9,10-anthraquinone derivatives is of particular interest since no known example has been documented. The synthesis of these N-glycosylated heterocyclic compounds using traditional glycosylation methods could be challenging. Therefore, our diversity-oriented protocols can be viewed as an alternative and practical glycosylation approach. In addition, we have also demonstrated that alkyl azides can also undergo the same cycloaddition, further expanding the structural repertoire available for a broader interest. Initial anticancer assays have revealed that 19f and 19k exert mean growth percent of 17.58 and −5.95, respectively.
Zhang, J.; Chang, C.-W. T. “Divergent Synthesis of Three Classes of Aryl N-Glycosides by Solvent Control.” J. Org. Chem. 2009, 74, 685-695. PubMed PMID: 19132944
PubMed PMID: 19132944