John D. Prugh

Utilization of the chiral synthon, methyl 3-O-benzyl-2,4,6-trideoxy-6-iodo-α-D-erythro-hexopyranoside in the synthesis of a potent HMG-CoA reductase inhibitor

Abstract Compound 1 , a potent synthetic HMG-CoA reductase inhibitor, has been synthesized from the chiral synthon, methyl 3-O-benzyl-2,4,6-trideoxy-6-iodo-α-D- erythro -hexopyranoside ( 2 ), utilizing a novel palladium-mediated procedure for benzyl ether cleavage.

A convenient synthesis of 5-substituted-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-ones via a chemoselective differentiation of the two ester functions of dimethyl acetonedicarboxylate

Abstract Dimethyl acetonedicarboxylate formed the enamine1 with benzylamine and thereby converted one of the carbomethoxy groups into a less electrophilic vinylogous urethane. Subsequent sequential alkylation of the active methylene moiety, chemoselective NaBH4 reduction of the ester function, hydrolysis of the enamine moiety and reduction of the newly generated keto group afforded alcohols 5 . Hydrolysis of the ester and lactonization gave the readily separable cis and trans lactones 8 ˜ and 9 ˜ .

Chapter 17. Progress in Atherosclerosis Therapy: Hypolipidemic Agents

Publisher Summary The importance of the lipoprotein transport system to the regulation of plasma lipid levels in human is firmly established. This system is responsible for delivering triglycerides (TG) primarily to adipose and muscle tissues and for continuously shuttling cholesterol between intestine, liver, and extrahepatic tissues. The localized deposition of plasma lipids, primarily cholesteryl esters, in the intima of the arterial wall accompanies formation of the atheromatous plaque or atheroma, the characteristic lesion of atherosclerosis growth of the atheroma eventually leads to constriction of the coronary arterial lumen, and ultimately results in coronary heart disease (CHD). Statistical along with compelling epidemiological evidence implicating hypercholesterolemia as a primary risk factor for CHD have provided impetus for the development of therapeutic approaches to the prevention and treatment of atherosclerosis based on the attenuation of plasma cholesterol levels. Epidemiologically documented, major risk factors for the development of atherosclerosis and CHD include hypertension, smoking, diabetes mellitus, obesity, age, sex, and hyperlipoproteinemia. Less well established are positive correlations between CHD and dietary intake of saturated animal fat or type A social behavior. In contrast, plasma high-density lipoproteins (HDL) levels are inversely correlated with CHD, a finding that has greatly stimulated research on HDL metabolism and function.