Attempts were made to minimize the
amounts of catalyst and solvent in the NHC-catalyzed benzoin reactions
of solid aldehydes. In some case, solid-to-solid conversions proceeded
in the solvent-free NHC-catalyzed benzoin reactions. Even if a mixture
of the substrate, N-heterocyclic carbene (NHC) precursor,
and inorganic base was initially a powdery solid, the reaction did
proceed at reaction temperature lower than the melting points of each
compound. The solid mixture partially melted or became a slurry or
suspension in the meantime. We call this solid/liquid mixture a semisolid
state. The reaction giving an optically active product was faster
than that giving a racemic mixture of the same product. Melting-point
depression was observed for a series of mixtures of the substrate
and product in different substrate/product ratios. Solvent-free solid-to-solid
conversions were accelerated by the formation of a semisolid state
resulting from the melting-point depression of the solid substrate
accompanied by the product formation. In the case of solid substrates
with high melting points, melting-point depression was useless, and
the addition of a small amount of solvent was needed. The first total
synthesis of isodarparvinol B was achieved via the NHC-catalyzed intramolecular
benzoin reaction using a small amount of solvent as an additive.
Industrial enzymes lipase PS (LPS) and lipase AK (LAK), which originate from Burkholderia cepacia and Pseudomonas fluorescens, respectively, are synthetically useful biocatalysts. To strengthen their catalytic performances, we introduced two mutations into hot spots of the active sites (residues 287 and 290). The LPS_L287F/I290A double mutant showed high catalytic activity and enantioselectivity for poor substrates for which the wild-type enzyme showed very low activity. The LAK_V287F/I290A double mutant was also an excellent biocatalyst with expanded substrate scope, which was comparable to the LPS_L287F/I290A double mutant. Thermodynamic parameters were determined to address the origin of the high enantioselectivity of the double mutant. The ΔΔH term, but not the ΔΔS term, was predominant, which suggests that the enantioselectivity is driven by a differential energy associated with intermolecular interactions around Phe287 and Ala290. A remarkable solvent effect was observed, giving a bell-shaped profile between the E values and the log P or ε values of solvents with the highest E value in i-PrO. This suggests that an organic solvent with appropriate hydrophobicity and polarity provides the double mutant with some flexibility that is essential for excellent catalytic performance.
A case of sclerosing cholangitis is presented. The patient was a 65 year‐old male and visited a hospital because symptoms of a biliary tract infection suddenly appeared. These symptoms improved in the short term with antibiotic therapy. As a high level of serum CA19–9 was found and the double wall structure of the intrahepatic bile duct and a portal thrombus were observed during an abdominal ultrasonography, the patient was transferred to our clinic for further examination of his hepatobiliary system. A malignant lesion was suspected from an endoscopic retrograde cholangiography and celiac angiography, although the patient's serum CA19–9 level rapidly decreased after admission. A liver with a smooth surface, some focal wide depressions, and an increase of white markings was observed laparoscopically. An adenomyomatosis‐like lesion was observed in the gallbladder. Bile duct destruction with periductar fibrosis was histologically proven. This is a case of histologically diagnosed sclerosing cholangitis but without the typical findings usually found during an endoscopic retrograde cholangiography.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.