Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent
摘要:
A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl chain tether and substituted phenyl group as a lipophilic tail have been prepared as agonists of PPAR alpha and gamma. c-5-[6-(4-Methanesulfonyloxyphenyl) hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid 13c exhibited potent hypoglycemic and lipid lowering activity with high oral bioavailability in animal models. (C) 2008 Elsevier Ltd. All rights reserved.
作者:Thomas J. A. Graham、Thomas H. Poole、Charles N. Reese、Brian C. Goess
DOI:10.1021/jo200262r
日期:2011.5.20
A one-pot, three-step strategy for the regioselective semihydrogenation of dienes is described. This procedure uses 9-BBN-H as a temporary protective group for alkenes. Yields range from 55% to 95%, and the reaction is tolerant of a variety of common functional groups. Additionally, the final elimination step of the sequence can be replaced with a peroxide-mediated alkylborane oxidation, generating regioselectively semihydrogenated product alcohols.