Catalytic, enantioselective N-acylation of lactams and thiolactams using amidine-based catalysts.

In contrast to alcohols and amines, racemic lactams and thiolactams cannot be resolved directly via enzymatic acylation or classical resolution. Asymmetric N-acylation promoted by amidine-based catalysts, particularly Cl-PIQ 2 and BTM 3, provides a convenient method for the kinetic resolution of these valuable compounds and often achieves excellent levels of enantioselectivity in this process. Density functional theory calculations indicate that the reaction occurs via N-acylation of the lactim tautomer and that cation-π interactions play a key role in the chiral recognition of lactam substrates.

Kinetic resolution of secondary alcohols using amidine-based catalysts.

Kinetic resolution of racemic alcohols has been traditionally achieved via enzymatic enantioselective esterification and ester hydrolysis. However, there has long been considerable interest in devising nonenzymatic alternative methods for this transformation. Amidine-based catalysts (ABCs), a new class of enantioselective acyl transfer catalysts developed in our group, have demonstrated, inter alia, high efficacy in the kinetic resolution of benzylic, allylic, and propargylic secondary alcohols and 2-substituted cycloalkanols, and thus provide a viable alternative to enzymes.

Plasmodium food vacuole plasmepsins are activated by falcipains.

Intraerythrocytic malaria parasites use host hemoglobin as a major nutrient source. Aspartic proteases (plasmepsins) and cysteine proteases (falcipains) function in the early steps of the hemoglobin degradation pathway. There is extensive functional redundancy within and between these protease families. Plasmepsins are synthesized as integral membrane proenzymes that are activated by cleavage from the membrane. This cleavage is mediated by a maturase activity whose identity has been elusive. We have used a combination of cell biology, chemical biology, and enzymology approaches to analyze this processing event. These studies reveal that plasmepsin processing occurs primarily via the falcipains; however, if falcipain activity is blocked, autoprocessing can take place, serving as an alternate activation system. These results establish a further level of redundancy between the protease families involved in Plasmodium hemoglobin degradation.

Kinetic resolution of 2-oxazolidinones via catalytic, enantioselective N-acylation.

Kinetic resolution of racemic 2-oxazolidinones via catalytic, enantioselective N-acylation has been achieved for the first time and with outstanding selectivities.

2,3-Dihydroimidazo[1,2-a]pyridines: a new class of enantioselective acyl transfer catalysts and their use in kinetic resolution of alcohols.

The long-known, but previously unexplored 2,3-dihydroimidazo[1,2-a]pyridine (DHIP) has been shown to be a competent acyl transfer catalyst. Its chiral 2-phenyl derivatives obtainable in two steps from commercially available starting materials have proved to be effective acylation catalysts, giving high levels of enantioselectivity (s = 20-85) in kinetic resolution of secondary benzylic alcohols. A transition state model explaining the observed selectivity has been proposed.

Parallel approach to selective catalysts for palladium-catalyzed desymmetrization of 2,4-cyclopentenediol.

[reaction: see text] Work toward the development of a bis-phosphine ligand system for the palladium-catalyzed desymmetrization of meso-diols is reported. A parallel approach using phosphine-containing amino acids and a "representational search" was taken to find a polymer-supported catalyst system. The selectivities reported are comparable to many other polymer-bound asymmetric catalysts.