Asymmetric synthesis of enantiomerically pure zingerols by lipase-catalyzed transesterification and efficient synthesis of their analogues

The achiral zingerone 1, readily available from ginger, can be easily transformed into chiral derivatives. Zingerol 2, a reduced product of zingerone 1 is expected to be an important new medicinal lead compound. We have achieved a concise synthesis of optically active zingerol (R)-2 and (S)-2 by the lipase-catalyzed stereoselective transesterification of racemic 2. Under the optimized conditions, a lipase from Alcaligenes sp. (Meito QLM) and vinyl acetate in i-Pr₂O or hexane at 35 °C within 1 h gave the alcohol (S)-2 and the acetate (R)-9 with high enantioselectivity without producing acetylated by-products. Since optically active (S)-2 and (R)-9 were obtained through lipase-catalyzed transesterification, other enantiomerically pure novel compounds could all be synthesized.     

Radiative X(3872) Decays in Charmonium-Molecule Hybrid Model

We study the radiative decays of the X(3872) in the charmonium-molecule model combined with the quark potential model. We obtain \({\Gamma(X(3872) \to J/\psi \, \gamma) = 29.2\,{\rm keV}}\) and \({\Gamma(X(3872) \to \psi' \, \gamma) = 6.3\,{\rm keV}}\) . The ratio of these two is 0.22, which is much smaller than the BABAR observation. We find that the result is very sensitive to the amount of the \({\chi_{c1}(1P)}\) component in the X(3872).     

Three new flavonoid glycosides, byzantionoside B 6'-O-sulfate and xyloglucoside of (Z)-hex-3-en-1-ol from Ruellia patula

Three new flavonoid glycosides, demethoxycentaureidin 7-O-β-D-galacturonopyranoside, pectolinarigenin 7-O-α-L-rhamnopyranosyl-(1?→4″)-β-D-glucopyranoside and 7-O-α-L-rhamnopyranosyl-(1?→4″)-β-D-glucuronopyranoside, a new megastigmane glucoside, byzantionoside B 6'-O-sulfate, and a new (Z)-hex-3-en-1-ol O-β-D-xylopyranosyl-(1″→2')-β-D-glucopyranoside, were isolated from leaves of Ruellia patula JACQ., together with 12 known compounds, β-sitosterol glucoside, vanilloside, bioside (decaffeoyl verbascoside), acteoside (verbascoside), syringin, benzyl alcohol O-β-D-xylopyranosyl-(1″→2')-β-D-glucopyranoside, cistanoside E, roseoside, phenethyl alcohol O-β-D-xylopyranosyl-(1″→2')-β-D-glucopyranoside, (+)-lyoniresinol 3α-O-β-D-glucopyranoside, isoacteoside and 3,4,5-trimethoxyphenol O-α-L-rhamnopyranosyl-(1″→6')-β-D-glucopyranoside. Their structures were elucidated by means of spectroscopic analyses.     

UCHP Method for Oligosaccharide Combinatorial Library Synthesis

A new methodology for oligosaccharide combinatorial library synthesis using a special hydroxy protecting group, the uni-chemo hydroxy protection (UCHP) group, was developed. The UCHP group was composed of oligomeric amino acid derivatives. The amino terminals of UCHP groups were protected by either Boc or Fmoc groups. By using these two types of UCHP, five kinds of trigalactoses [Galβ1-3Galβ1-3Gal, Galβ1-3(Galβ1-4)Gal, Galβ1-4Galβ1-3Gal, Galβ1-3Galβ1-4Gal, and Galβ1-4Galβ1-4Gal] were successfully synthesized on a solid support as a model of oligosaccharide combinatorial library. Each step of all reactions was also successfully monitored using a combination of two colorimetric tests, chloranil and methyl red-DIC.     

Thermal properties and detectability of neutron stars - I cooling and heating of neutron stars

In this report, we first review earlier and recent developments in some of thermodynamic problems of neutron stars, especially those involving cooling mechanisms and theoretical predictions of surface temperatures of neutron stars. Emphasis is placed particularly on: the effect of equations of state and hence that of nuclear and strong interactions; the effect of better treatment of various neutrino cooling mechanisms, especially those involving pion condensates; and implication of these better and more detailed theoretical estimates on the prospect of directly observing thermal radiation from the surface of neutron stars. In connection with the last problem, we briefly review recent developments on the observational side — the HEAO-B and other programs already existing or expected to be planned for near future, which are directly related to the above problem. In connection with the possibilities of observing older neutron stars we briefly summarise various heating mechanisms.From these studies, we see that exciting possibilities exist through the HEAO-B and some other programs which may be realised in the 1980's, that we may observe radiation directly from neutron star surfaces if they are ? (3?5) × 10⁵°K. If such radiation is detected, the observed surface temperatures and further spectral studies may give invaluable insight into various important problems, such as magnetic properties of dense matter, equations of state, pion condensates, and other fundamental problems in nuclear, particle and high energy physics. If the surface temperatures of younger members of these stars (? 10⁴ years) are observationally found to be less than ≈ (5?10) × 10⁵°K (depending on the individual objects), we note that at the moment only pion coolings are consistent with observations, and the outcome may be equally far reaching. Among various observed neutron stars (pulsars) and neutron star candidates (e.g. supernova remnants), the Vela pulsar may prove to be the most rewarding one. If regular pulsar-like periodicities are discovered in radiations from any of supernova remnants, we can assume the presence of neutron stars in these objects. In that case, some supernova remnants, such as SN 1006, may also turn out to be promising. If we defect surface radiations from older pulsars (? 10⁵ years), that may support some of heating theories. At the end, we point out that there may be many point sources of very soft weak thermal X-rays across the sky (as old neutron stars accrete interstellar matter) and some of the closest ones may be detectable through the HEAO-B and similar devices.     

Pi-interaction tuning of the active site properties of metalloproteins

The influence of pi-interactions with a His ligand have been investigated in a family of copper-containing redox metalloproteins. The Met16Phe and Met16Trp pseudoazurin, and Leu12Phe spinach and Leu14Phe Phormidium laminosum plastocyanin variants possess active-site pi-contacts between the introduced residue and His81 and His87/92 respectively. The striking overlap of the side chain of Phe16 in the Met16Phe variant and that of Met16 in wild type pseudoazurin identifies that this position provides an important second coordination sphere interaction in both cases. His-ligand protonation and dissociation from Cu(I) occurs in the wild type proteins resulting in diminished redox activity, providing a [H(+)]-driven switch for regulating electron transfer. The introduced pi-interaction has opposing effects on the pKa for the His ligand in pseudoazurin and plastocyanin due to subtle differences in the pi-contact, stabilizing the coordinated form of pseudoazurin whereas in plastocyanin protonation and dissociation is favored. Replacement of Pro36, a residue that has been suggested to facilitate structural changes upon His ligand protonation, with a Gly, has little effect on the pKa of His87 in spinach plastocyanin. The mutations at Met16 have a significant influence on the reduction potential of pseudoazurin. Electron self-exchange is enhanced, whereas association with the physiological partner, nitrite reductase, is only affected by the Met16Phe mutation, but kcat is halved in both the Met16Phe and Met16Trp variants. Protonation of the His ligand is the feature most affected by the introduction of a pi-interaction.     

Design of peptides that form amyloid-like fibrils capturing amyloid beta1-42 peptides

Amyloid beta-peptide (Abeta) plays a critical role in Alzheimer's disease (AD). The monomeric state of Abeta can self-assemble into oligomers, protofibrils, and amyloid fibrils. Since the fibrils and soluble oligomers are believed to be responsible for AD, the construction of molecules capable of capturing these species could prove valuable as a means of detecting these potentially toxic species and of providing information pertinent for designing drugs effective against AD. To this aim, we have designed short peptides with various hydrophobicities based on the sequence of Abeta14-23, which is a critical region for amyloid fibril formation. The binding of the designed peptides to Abeta and the amplification of the formation of peptide amyloid-like fibrils coassembled with Abeta are elucidated. A fluorescence assay utilizing thioflavin T, known to bind specifically to amyloid fibrils, revealed that two designed peptides (LF and VF, with the leucine and valine residues, respectively, in the hydrophobic core region) could form amyloid-like fibrils effectively by using mature Abeta1-42 fibrils as nuclei. Peptide LF also coassembled with soluble Abeta oligomers into peptide fibrils. Various analyses, including immunostaining with gold nanoparticles, enzyme-linked immunosorbent assays, and size-exclusion chromatography, confirmed that the LF and VF peptides formed amyloid-like fibrils by capturing and incorporating Abeta1-42 aggregates into their peptide fibrils. In this system, small amounts of mature Abeta1-42 fibrils or soluble oligomers could be transformed into peptide fibrils and detected by amplifying the amyloid-like fibrils with the designed peptides.     

Bioactive constituents from Chinese natural medicines. XX. Inhibitors of antigen-induced degranulation in RBL-2H3 cells from the seeds of Psoralea corylifolia

The ethyl acetate-soluble fraction of the methanolic extract from the seeds of Psoralea corylifolia was found to inhibit the release of beta-hexosaminidase, as a marker of antigen-IgE-induced degranulation in RBL-2H3 cells. Sixteen constituents were isolated from the ethyl acetate-soluble fraction and several constituents, Delta(1),3-hydroxybakuchiol (IC(50) = 49 microM), Delta(3),2-hydroxybakuchiol (69 microM, bavachin (58 microM), and psoralidin (ca. 100 microM), showed inhibitory activities against the antigen-induced degranulation.     

Medicinal flowers. XVII. New dammarane-type triterpene glycosides from flower buds of American ginseng, Panax quinquefolium L

Five new dammarane-type triterpene glycosides, floralquinquenosides A, B, C, D, and E, were isolated from the flower buds of American ginseng, Panax quinquefolium L., together with 18 known dammarane-type triterpene glycosides and 3 flavonoid glycosides. The structures of new floralquinquenosides were elucidated on the basis of chemical and physicochemical evidence.     

Improvement in the quality of hematopoietic prostaglandin D synthase crystals in a microgravity environment

Human hematopoietic prostaglandin synthase, one of the better therapeutic target enzymes for allergy and inflammation, was crystallized with 22 inhibitors and in three inhibitor-free conditions in microgravity. Most of the space-grown crystals showed better X-ray diffraction patterns than the terrestrially grown ones, indicating the advantage of a microgravity environment on protein crystallization, especially in the case of this protein.