A Bidirectional S_E′ Strategy for 1,5-<i>syn</i> and 1,5-<i>anti</i> Stereocontrol toward the Synthesis of Complex Polyols

Studies report a bidirectional S_E′ strategy applicable for the stereocontrolled synthesis of nonracemic 1,5-<i>syn</i> and 1,5-<i>anti</i> diols and their derivatives. Nonracemic 1,3,2-diazaborolidine auxiliaries are incorporated by chemoselective tin–boron exchange to provide reactive allylic boranes. The convergent pathway utilizes sequential reactions with two aldehydes producing stereochemical outcomes from cyclic, closed, and open transition state preferences, respectively. Synthesis of fragment <b>16</b> of peloruside A is accomplished in four steps from readily available aldehydes <b>9</b> and <b>13</b>

Development of Novel Benzomorpholine Class of Diacylglycerol Acyltransferase I Inhibitors

Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential therapeutic target for obesity and diabetes for its important role in triglyceride biosynthesis. Herein we report the rational design of a novel class of DGAT1 inhibitors featuring a benzomorpholine core (<b>23n</b>). SAR exploration yielded compounds with good potency and selectivity as well as reasonable physical and pharmacokinetic properties. This class of DGAT1 inhibitors was tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the treatment of metabolic diseases. Compound <b>23n</b> conferred weight loss and a reduction in liver triglycerides when dosed chronically in mice with diet-induced obesity and depleted serum triglycerides following a lipid challenge