Enantioselective construction of nitrogen-substituted quaternary carbon centers adjacent to the carbonyl group in the cyclohexane ring was performed with respect to the asymmetric synthesis of anesthetic (S)-ketamine 1. Diastereoselective nucleophilic 1,2-addition reaction of phenyllithium to α-ketoxime-ether acetal 9 bearing chiral auxiliary on the α-carbonyl function gave benzyloxyamine 11 major in 83% yield with 82% de, which was converted to the corresponding amino ketone 12.However, the reaction of 2-chlorophenyllithium did not work in which this route was unavailable for the synthesis of 1. Then, an alternative strategy directed toward 1, starting with a compound having 2-chlorophenyl groups in advance, was designed so that the chiral quaternary carbon center bearing a nitrogen atom in the ring is created by the enantioselective reduction of the atropisomeric intermediate ketone 18, and the sequential allyl cyanate-to-isocyanate rearrangement with complete 1,3-chirality transfer. The first asymmetric synthesis of 1 with excellent selectivity (>99% ee) was accomplished by a short path according to the strategy.

Abstract--[IrCl(cod)] 2 catalyzed the oxidative esterification of a variety of aldehydes with methanol as a solvent in combination of K 2 CO 3 under mild conditions (rt, 12 h). The oxidative esterification reaction of aliphatic aldehydes also took place with olefinic alcohols as reagents in toluene under similar conditions.

A 48-year-old Japanese female with left hypochondralgia presented at our hospital. Esophagogastroduodenoscopy (EGD) revealed gastric cancers and carpeting fundic gland polyposis (FGPs) without Helicobacter pylori infection. Computed tomography showed multiple liver metastases. Total colonoscopy revealed a colonic tubular adenoma but not polyposis. She was diagnosed as having advanced gastric cancer with liver metastasis and received chemotherapy. Her mother had died from gastric cancer, and her elderly brother and niece had FGPs as revealed by EGD. Thus, the pedigree was diagnosed as gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Germline mutation analysis exhibited a point mutation in exon1B of the APC gene (c.-191T > C). Adenocarcinoma showed a gastric mucinous phenotype and was positive for a somatic mutation of p53, suggesting that p53 mutation may play a role in FGPs carcinogenesis. This is the first family with GAPPS in Asia in whom germline mutation of APC exon 1B has been detected.

SummaryWe hypothesized that, with oral or intestinal administration of amino acids (AA), we may reduce hypothermia during general anesthesia as effectively as with intravenous AA. We, therefore, examined the effect of bolus oral and continuous intestinal AA in preventing hypothermia in rats. Male Wistar rats were anesthetized with sevoflurane for induction and with propofol for maintenance. In the first experiment, 30 min before anesthesia, rats received one bolus 42 mL/kg of AA solution

The stereocenter in the intermediate alcohol (86% ee), created by enantioselective oxazaborolidinone-promoted aldol reaction, was transferred to the stereocenter in the cyclohexanone ring, necessary for (S)-ketamine, via allyl cyanate-to-isocyanate rearrangement. The second asymmetric synthesis of (S)-ketamine has been achieved (87% ee).