Non-C2-Symmetric Bis-Benzimidazolium Salt Applied in the Synthesis of Sterically Hindered Biaryls.

A novel non-C2-symmetric bis-benzimidazolium salt derived from (±)-valinol has been prepared by a simple and straightforward process in good yield. The structure of bis-benzimidazolium salt provided a bulky steric group on the ethylene bridge; which facilitates the catalytic efficacy in the C(sp2)-C(sp2) formation. Its catalytic activity in Suzuki-Miyaura cross-coupling reaction of unactivated aryl chlorides has been found to have high efficacy in 1 mol% Pd loading. This protocol demonstrated the potential on the synthesis of sterically hindered biaryls.

An efficient class of bis-NHC salts: applications in Pd-catalyzed reactions under mild reaction conditions.

This study describes an efficient class of bis-N-heterocyclic carbene (bis-NHC) salts that can be easily made from commercially available and inexpensive starting materials. The application of these salts to Pd-catalyzed reactions is described. The palladium (Pd) catalyst generated in situ was highly effective under mild reaction conditions.

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Chiral O,N,O-tridentate Phenol Ligands Derived From Camphor.

Chiral O,N,O-tridentate phenol ligands bearing a camphor backbone were found to be effective chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in high enantioselectivities (80-95% ee) at room temperature.

Enantioselective reduction of ketones with borane catalyzed by tridentate amino alcohols derived from salicylaldehyde.

In the presence of tridentate chiral ligand 4e, 99% e.e. value was obtained by asymmetric reduction of ethyl benzoylacetate with borane in toluene at 25 degrees C. Various ligands and reaction conditions were investigated to develop a reasonable mechanism that explains the experimental outcomes.

Enantioselective synthesis of L-homophenylalanine by whole cells of recombinant Escherichia coli expressing L-aminoacylase and N-acylamino acid racemase genes from Deinococcus radiodurans BCRC12827.

L-Homophenylalanine (l-HPA) is a chiral unnatural amino acid used in the synthesis of angiotensin converting enzyme inhibitors and many pharmaceuticals. To develop a bioconversion process with dynamic resolution of N-acylamino acids for the l-HPA production, N-acylamino acid racemase (NAAAR) and l-aminoacylase (LAA) genes were cloned from Deinococcus radiodurans BCRC12827 and expressed in Escherichia coli XLIBlue. The recombinant enzymes were purified by nickel-chelate chromatography, and their biochemical properties were determined. The NAAAR had high racemization activity toward chiral N-acetyl-homophenylalanine (NAc-HPA). The LAA exhibited strict l-enantioselection to hydrolyze the NAc-l-HPA. A stirred glass vessel containing transformed E. coli cells expressing D. radiodurans NAAAR and LAA was used for the conversion of NAc-d-HPA to l-HPA. Unbalance activities of LAA and NAAAR were found in E. coli cell coexpressing laa and naaar genes, which resulted in the accumulation of an intermediate, NAc-l-HPA, in the early stage of conversion and a low productivity of 0.83 mmol l-HPA/L h. The results indicated that low activity of LAA present in the biomass is the rate-limiting factor in l-HPA production. In the case of two whole cells with separately expressed enzyme, the enzymatic activities of LAA and NAAAR could be balanced by changing the loading of individual cells. When the activities of two enzymes were fixed at 3600 U/L, 99.9% yield of l-HPA could be reached in 1 h, with a productivity of 10 mmol l-HPA/L h. The cells can be reused at least six cycles at a conversion yield of more than 96%. This is the first NAAAR/LAA process using NAc-HPA as substrate and recombinant whole cells containing Deinococcus enzymes as catalysts for the production of l-HPA to be reported.

Enantioselective synthesis of (S)-2-amino-4-phenylbutanoic acid by the hydantoinase method.

Biosynthesis of (S)-(+)-2-amino-4-phenylbutanoic acid (1) was performed by nonenantioselective hydantoinase and L-N-carbamoylase using racemic 5-[2-phenylethyl]-imidazolidine-2,4-dione (rac-2) as a substrate. The compounds involved in this biocatalysis process could be simultaneously resolved by high-performance liquid chromatography using Chirobiotic T column with a mobile phase of EtOH/H(2)O = 10/90 at pH 4.2-4.5. To our knowledge, this is the first report of the successful production of 1 by the combination of recombinant hydantoinase and L-N-carbamoylase.