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Despite extensive studies into the design of effective chiral catalysts for asymmetric halolactonizations, the development of highly enantioselective catalytic bromolactonization of 4‐aryl‐4‐pentenoic acids, which is one of the benchmark reactions, has not been completely satisfactory. Herein, we report the use of BINOL‐derived chiral bifunctional sulfide catalysts to achieve highly enantioselective bromolactonizations of 4‐aryl‐4‐pentenoic acids. The importance of the bifunctional design of chiral sulfide catalysts was clearly demonstrated in the present study. Furthermore, the present catalytic asymmetric reaction system could be applied to highly stereoselective desymmetrizing bromolactonizations. The highest reported enantioselective bromolactonization of 4‐aryl‐4‐pentenoic acidsto produce optically active γ‐butyrolactones was accomplished via the use of chiral bifunctional sulfide catalysts bearing a hydroxy group.

Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8and TRPA1mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 gkgday for 12 days) and Oxp (intraperitoneal dose: 4 mgkg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4–L6 DRG were removed and the expression of TRPM8and TRPA1mRNA was determined using RT-PCR. The expression of TRPM8and TRPA1in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8and TRPA1mRNA.

Effects of two kinds of quilt with different thermal insulation properties between the upper and lower halves on human core temperature during night sleep were compared at an ambient temperature of 16°C and a relative humidity of 50% in five healthy adult women. One quilt has a thick part ( 110 mm) in the upper half and a thin part ( 63 mm) in the lowest half ( Quilt A), and the other has a thin part ( 63 mm) in the upper half and a thick part ( 110 mm) in the lower half ( Quilt B). Subjects, wearing shirts with half-sleeves and breeches, slept on a bed with sleeping mat, being fully covered by either Quilt A or Quilt B from 22:00 to 06:00. The major finding was that rectal temperature fell more quickly in Quilt B after retiring at 22:00, being kept at a lower level during one third of the whole night. We suggest that the reduced level of rectal temperature in Quilt B might be ascribed to lower thermal insulation in the upper half side of the Quilt B and partly to different core-peripheral blood redistribution in the lower extremities between the two kinds of quilt. Rapid fall and lowered level rectal temperature in Quilt B might be of significance for ease in sleep onset and sleep depth