Title | Structural, Mechanistic, and Computational Analysis of the Effects of Anomeric Fluorines on Anomeric Fluoride Departure in 5-Fluoroxylosyl Fluorides |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Lee, SSeo, Greig, IR, Vocadlo, DJ, McCarter, JD, Patrick, BO, Withers, SG |
Journal | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY |
Volume | 133 |
Pagination | 15826-15829 |
Date Published | OCT 12 |
ISSN | 0002-7863 |
Abstract | The effects of fluorine substitution at the C-5 center of pyranosyl fluorides on the reactivity at the C-1 anomeric center was probed by studying a series of 5-fluoroxylosyl fluoride derivatives. X-ray structures of their per-O-acetates detailed the effects on the ground-state structures. First-order rate constants for spontaneous hydrolysis, in conjunction with computational studies, revealed that changes in the stereochemistry of the 5-fluorine had minimal effects on the solvolysis rate constants and that the observed rate reductions were broadly similar to those caused by additional fluorine substitution at C-1 but significantly less than those due to substitution at C-2. Differences in the trapping behavior of 5- versus 2-fluoro-substituted glycosyl fluorides with alpha- and beta-glycosidases arise more from differences in steric effects and hydrogen-bonding interactions than from intrinsic reactivity differences. |
DOI | 10.1021/ja204829r |