Bis(oxazoline)–ligand-mediated asymmetric [2,3]-Wittig rearrangement of benzyl ethers: reaction mechanism based on the hydrogen/deuterium exchange effect

We have investigated the mechanism of chiral induction in the asymmetric [2,3]-Wittig rearrangement of allyl benzyl ether in the presence of a bis(oxazoline) chiral ligand [(S,S)-Box–tBu] by comparing the reaction of both enantiomers of monodeuterated benzyl ether 1a–d. As a result, we found that chirality was induced via enantioselective deprotonation followed by efficient chirality transfer of the resulting chiral benzyl carbanion with the inversion of stereochemistry. It was revealed that the chiral ligand facilitates selective deprotonation as well as prevents the chiral carbanion from racemization. Moreover, we examined the effect of the o-methoxy substituent on the benzene ring.     

Correlation analyses on binding affinity of sialic acid analogues and anti-influenza drugs with human neuraminidase using ab initio MO calculations on their complex structures--LERE-QSAR analysis (IV)

We carried out full ab initio fragment molecular orbital (FMO) calculations for complexes comprising human neuraminidase-2 (hNEU2) and sialic acid analogues including anti-influenza drugs zanamivir (Relenza) and oseltamivir (Tamiflu) in order to examine the variation in the observed inhibitory activity toward hNEU2 at the atomic and electronic levels. We recently proposed the LERE (linear expression by representative energy terms)-QSAR (quantitative structure-activity relationship) procedure. LERE-QSAR analysis quantitatively revealed that the complex formation is driven by hydrogen-bonding and electrostatic interaction of hNEU2 with sialic acid analogues. The most potent inhibitory activity, that of zanamivir, is attributable to the strong electrostatic interaction of a positively charged guanidino group in zanamivir with negatively charged amino acid residues in hNEU2. After we confirmed that the variation in the observed inhibitory activity among sialic acid analogues is excellently reproducible with the LERE-QSAR equation, we examined the reason for the remarkable difference between the inhibitory potencies of oseltamivir as to hNEU2 and influenza A virus neuraminidase-1 (N1-NA). Several amino acid residues in close contact with a positively charged amino group in oseltamivir are different between hNEU2 and N1-NA. FMO-IFIE (interfragment interaction energy) analysis showed that the difference in amino acid residues causes a remarkably large difference between the overall interaction energies of oseltamivir with hNEU2 and N1-NA. The current results will be useful for the development of new anti-influenza drugs with high selectivity and without the risk of adverse side effects.     

On the surface chemical reactions of metal and oxide XPS samples at 300–400° at a high vacuum produced by oil diffusion pumps

Metal and oxide surface reactions formed by heating in the spectrometer at 300–400° at a vacuum of ca. 10^?9 Torr (oil diffusion pumps) were studied. As a result of spectral observations before and after heating, the metals studied were classified into five groups. In the first group, oxide films on the metal surface are easily evaporated because of the high vapour pressure of oxide; in the second, the oxide films are easily reduced in the spectrometer; in the third, the oxide film formed on the metal is reduced but the bulk oxide is not easily reduced; in the fourth, very stable oxide films are formed and the bulk oxide is also stable; and finally in the fifth, the oxide film formed on the metal is apparently reduced, yet the bulk oxide is very stable.     

Increased gamma-aminobutyrate aminotransferase activity in brain of patients with Alzheimer's disease

In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma-aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter.