Preparation of optically active succinic acid derivatives. III. Regioselective condensation reactions of optically active 2-substituted succinic acids with diimidazolide

We investigated the large scale synthesis of monocalcium bis [(2S)-2-benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl) propionate] dihydrate (KAD-1229), which has a potent hypoglycemic effect, in a single reaction vessel. (2S)-2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl) propionic acid (7) was directly obtainable from (S)-2-benzylsuccinic acid (2) and cis-hexahydroisoindoline (4), without the isolation of intermediates by the method using thionyldiimidazole (9) and/or diimidazolide of the acid 2. Sequential reaction of imidazole with thionyl chloride, 2, and 4, followed by acid catalyzed hydrolysis gave amidecarboxylic acid 7 in 86% overall yield. The acid 7 was treated with 2 N NaOH, followed by the treatment with calcium chloride to give KAD-1229 in 91% yield.     

Electrically active point defects in cadmium telluride

Hall coefficient and conductivity measurements were made on single crystals of CdTe at temperatures up to 950°C while controlling the partial pressure of either cadmium or tellurium. Measurements made with a cadmium reservoir showed the material to ben-type due to the presence of a doubly ionized native donor, in agreement with the results of Whelan and Shaw. The apparent enthalpy of formation of the donor and its concentration along the cadmium-rich solidus were obtained. Measurements made with a tellurium reservoir close to tellurium saturation are in disagreement with the usual model, which attributes formation ofp-type material under these conditions to the presence, of a native acceptor defect. The results are consistent with a hole concentration originating from an excess of acceptor impurities rather than from a native acceptor.     

Synthesis of optically active alpha-(p-chlorophenyl)pyridylmethanols with plant cell cultures

We report here on the mapping of a cDNA encoding for human cysteine-rich heart protein (HCRHP), a counterpart of the murine cysteine-rich intestinal protein CRIP. By somatic cell hybrid analysis and radiation hybrid mapping, we have located the gene CRIP1 (HGMW-approved symbol) on the subcentromeric region of the q arm of human chromosome 7, flanking a deletion associated with Williams syndrome.     

Preparation of optically active proline. Optical resolution of N-acyl-DL-proline by preferential crystallization procedure

Cross reactivity of prednisolone with an antiserum raised against dexamethasone-21-hemisuccinate conjugated with bovine serum albumin was utilized to develop a radioimmunoassay for prednisolone in unextracted plasma. The results are in good agreement with those obtained with a standard competitive protein binding method employing prior extraction and separation of the synthetic from endogenous steroids.     

Potential and limitations of an optically active crown ether for chiral separation in capillary zone electrophoresis

Capillary zone electrophoresis using optically active 18-crown-6 tetracarboxylic acid (18C6H4) as chiral selector was studied for the enantiomeric separation of primary amines. From the separation of a variety of pharmaceutical drug substances, amino alcohols and amino acids, conclusions could be made concerning the influence of the chemical structure of the analytes on the separation. In addition, the effects of experimental parameters such as pH, proportion of organic modifier and buffer composition on the separation are discussed. A synergistic effect obtained by the joint application of 18C6H4 and a cyclodextrin was exploited to resolve analytes which were separated neither by the crown ether nor by the cyclodextrin.     

In vitro and in vivo antidermatophyte activities of NND-502, a novel optically active imidazole antimycotic agent

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against Trichophyton spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.     

Synthesis of optically active amino acids from alpha-keto acids with Escherichia coli cells expressing heterologous genes

We describe a simple method for enzymatic synthesis of L and D amino acids from alpha-keto acids with Escherichia coli cells which express heterologous genes. L-amino acids were produced with thermostable L-amino acid dehydrogenase and formate dehydrogenase (FDH) from alpha-keto acids and ammonium formate with only an intracellular pool of NAD+ for the regeneration of NADH. We constructed plasmids containing, in addition to the FDH gene, the genes for amino acid dehydrogenases, including i.e., leucine dehydrogenase, alanine dehydrogenase, and phenylalanine dehydrogenase. L-Leucine, L-valine, L-norvaline, L-methionine, L-phenylalanine, and L-tyrosine were synthesized with the recombinant E. coli cells with high chemical yields (> 80%) and high optical yields (up to 100% enantiomeric excess). Stereospecific conversion of various alpha-keto acids to D amino acids was also examined with recombinant E. coli cells containing a plasmid coding for the four heterologous genes of the thermostable enzymes D-amino acid aminotransferase, alanine racemase, L-alanine dehydrogenase, and FDH. Optically pure D enantiomers of glutamate and leucine were obtained.