Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL).

High serum fatty acid (FA) levels are causally linked to the development of insulin resistance, which eventually progresses to type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) generalized in the term metabolic syndrome. Adipose triglyceride lipase (ATGL) is the initial enzyme in the hydrolysis of intracellular triacylglycerol (TG) stores, liberating fatty acids that are released from adipocytes into the circulation. Hence, ATGL-specific inhibitors have the potential to lower circulating FA concentrations, and counteract the development of insulin resistance and NAFLD.

Chiral Discrimination in Rhodium(I) Catalysis by 2,5-Disubstituted 1,3,4,6-Tetrahydropenatalene Ligands-More Than Just a Twist of the Olefins?

Chiral dienes are useful ligands in a number of asymmetric transition-metal-catalyzed reactions. Here, we evaluate the efficiency of 2,5-disubstituted 1,3,4,6-tetrahydropentalenes as ligands to rhodium(I). 2,5-Dibenzyl and diphenyl tetrahydropentalenes were synthesized in two steps and resolved, either chromatographically, or through fractional crystallization of diastereomeric rhodium(I) salts.

Control of Enantioselectivity in Rhodium(I) Catalysis by Planar Chiral Dibenzo[a,e]cyclooctatetraenes.

Planar chiral 5,11-disubstiuted dibenzo[a,e]cyclo-octatetraenes (dbCOTs) have been developed as the first useful chiral homologs to dbCOT-ligands for asymmetric applications. Methods enabling the preparation of such compounds on a gram-scale in enantiomerically pure form are described. Evaluated as ligands in rhodium(I)-catalyzed 1,4- and 1,2-arylation reactions, tertiary and quarternary stereogenic centers were formed with excellent yields and selectivities of up to >99 % ee.

Structure-activity studies in the development of a hydrazone based inhibitor of adipose-triglyceride lipase (ATGL).

Adipose triglyceride lipase (ATGL) catalyzes the degradation of cellular triacylglycerol stores and strongly determines the concentration of circulating fatty acids (FAs). High serum FA levels are causally linked to the development of insulin resistance and impaired glucose tolerance, which eventually progresses to overt type 2 diabetes. ATGL-specific inhibitors could be used to lower circulating FAs, which can counteract the development of insulin resistance.

Iridium catalyzed carbocyclizations: efficient (5+2) cycloadditions of vinylcyclopropanes and alkynes.

Third-row transition metal catalysts remain a largely untapped resource in cycloaddition reactions for the formation of medium-sized rings. Herein, we report the first examples of iridium-catalyzed inter- and intramolecular vinylcyclopropane (VCP)-alkyne (5+2) cycloadditions. DFT modeling suggests that catalysis by iridium(I) proceeds through a mechanism similar to that previously reported for rhodium(I)-catalyzed VCP-alkyne cycloadditions, but a smaller free energy span for iridium enables substantially faster catalysis under favorable conditions.