Shigeyasu Motohashi

Chirality in dynamic supramolecular nanotubes induced by a chiral solvent.

Amplification of chirality has been reported in polymeric systems. It has also been shown that related effects can occur in polymer-like dynamic supramolecular aggregates, if a subtle balance between noncovalent interactions allows the coupling between a chiral information and a cooperative aggregation process. In this context, we report a strong majority-rules effect in the formation of chiral dynamic nanotubes from chiral bisurea monomers. Furthermore, similar helical nanotubes (with the same circular dichroism signature) can be obtained from racemic monomers in a chiral solvent. Competition experiments reveal the relative strength of the helical bias induced by the chiral monomer or by the chiral solvent. The nanotube handedness is imposed by the monomer chirality, whatever the solvent chirality. However, the chirality of the solvent has a significant effect on the degree of chiral induction.

Cucurbitane Triterpenoids from the Leaves of Momordica charantia, and Their Cancer Chemopreventive Effects and Cytotoxicities

Seventeen cucurbitane‐type triterpenoids, 1–17, including six new compounds, (23E)‐3β,25‐dihydroxy‐7β‐methoxycucurbita‐5,23‐dien‐19‐al (1), (23S*)‐3β‐hydroxy‐7β,23‐dimethoxycucurbita‐5,24‐dien‐19‐al (6), (23R*)‐23‐O‐methylmomordicine IV (7), (25ξ)‐26‐hydroxymomordicoside L (8), 25‐oxo‐27‐normomordicoside L (9), and 25‐O‐methylkaravilagenin D (12), were isolated from a MeOH extract of the leaves of Japanese Momordica charantia. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Compounds 1–17 were examined for their inhibitory effects on EpsteinBarr virus early antigen (EBV‐EA) activation induced with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells, a known primary screening test for inhibitors of tumor promotion. Four compounds, 1, (23E)‐3β,7β‐dihydroxy‐25‐methoxycucurbita‐5,23‐dien‐19‐al (2), karavilagenin D (11), and 12, showed potent inhibitory effects on EBV‐EA induction with IC50 values in the range of 242–264 mol ratio/32 pmol TPA. In addition, compounds 1 and 11 exhibited inhibitory effects on skin‐tumor promotion in an in vivo two‐stage mouse skin carcinogenesis test based on 7,12‐dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as a promoter. Furthermore, upon evaluation of the cytotoxic activities of compounds 1–17 against human cancer cell lines, compounds 2, 5–7, 9, and 14 showed potent activities against HL60 cell line, and compound 2 against SK‐BR‐3 cell line.

Alkane diols from flower petals of Carthamus tinctorius

Abstract Eleven novel secondary alkane-1,3-diols were isolated from a methanol extract of dried flower petals of Carthamus tinctorius . Their structures were determined to be syn ( R , S and/or S , R )-C 36 -alkane-6,8-diol, syn -C 28 -, C 30 -, C 32 , C 34 ,- and C 36 -alkane-7,9-diols, and syn -C 27 , C 29 -, C 31 -, C 33 - and C 35 -alkane-8,10-diols by spectral methods.

A new reverse worm-like micellar system from a lecithin, multivalent carboxylic acid and oil mixture.

We developed new lecithin organogels composed of reverse worm-like micelles with lecithin/multivalent carboxylic acid/oil systems, and discussed their phase behavior and rheological properties. The most important findings in this study are the following. From a screening test of many carboxylic acids for gelation, it was found that the number and position of the carboxyl groups of the multivalent carboxylic acids are the determinants for the formation of reverse worm-like micelles, and appropriate carboxylic acids such as citric acid and 1,2,3-propanetricarboxylic acid can change the lecithin/oil solution into a gel. Furthermore, upon addition of these carboxylic acids, the zero-shear viscosity of solutions increased monotonically until phase separation or cloudiness occurred. For example, when citric acid was used, the maximum zero-shear viscosity of the solution was 70,000,000 times larger than that of n-decane. From studies on the scaling of rheological parameters, it was found that further addition of multivalent carboxylic acids not only induced the formation of linear reverse worm-like micelles but also brought about their branching.

Asymmetric Synthesis of γ-Hydroxy α-Enones by 1,8-Diazabicyclo[5.4.0]undec-7-ene-Catalyzed Stereoselective Rearrangement of Chiral α-Sulfinyl Enones

The asymmetric rearrangement of optically active alpha-sulfinyl enone 1 induced by catalytic DBU and triphenylphosphine gave optically active gamma-hydroxy alpha-enone derivatives (up to 99% ee) in good yield following treatment with aqueous hydrogen peroxide.

In Vitro and in Vivo Anti-Influenza Virus Activity of Diarylheptanoids Isolated from Alpinia Officinarum

Background: Diarylheptanoids (AO-0002 [7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-4E-hepten-3-one] and AO-0011 [(5S)-5-hydroxy-7-(4″-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated from Alpinia officinarum have been reported to exhibit anti-influenza virus activity in vitro. Hence, efficacies against influenza virus infection and the mode of antiviral action were evaluated in vivo and in vitro, respectively. Methods: In a murine influenza virus infection model, diarylheptanoids were orally administered three times daily to mice infected with influenza A/PR/8/34 virus for 6 days after infection. AO-0002 was examined for its antiviral activity against the wild types of influenza viruses A/PR/8/34 (H1N1), oseltamivir-resistant A/PR/8/34 (H1N1), A/Bangkok/93/03 (H1N1), A/Ishikawa/7/82 (H3N2), A/Fukushima/13/43 (H3N2), B/Singapore/222/79 and B/Fukushima/15/93 in plaque reduction or yield reduction assays. The mode of anti-influenza virus action was assessed by a virus adsorption assay, immunofluorescence assay of viral antigens, and inhibition of viral messenger RNA synthesis using real-time reverse transcriptase PCR. Results: AO-0002 at 100 mg/kg was significantly effective in reducing the body weight loss and prolonging survival times of infected mice without toxicity, but AO-0011 was not. AO-0002 at 30 and 100 mg/kg significantly reduced virus titres in bronchoalveolar lavage fluids of the lungs on days 3 and 6 after infection. AO-0002 exhibited anti-influenza virus activity against all viruses used, including the oseltamivir-resistant strain in vitro. The compound had no effect on virus adsorption or invasion into cells, but dose-dependently suppressed the expression of viral messenger RNA and antigens. Conclusions: AO-0002 was suggested to have a different anti-influenza virus action to that of oseltamivir and was verified to show anti-influenza activity in vitro and in vivo.

The asymmetric favorskii rearrangement: A synthesis of optically active α-alkyl amides from aldehydes and (−)-1-chloroalkyl p-tolyl sulfoxide

Abstract The first asymmetric Favorskii rearrangement is described. Optically active α-alkyl amides of enantiomeric excess up to 94% were realized from aldehydes and optically active (−)-1-chloroalkyl p-tolyl sulfoxides via the Favorskii rearrangement of optically active α-chloro α-sulfonyl ketones.

A novel synthesis of α, β-unsaturated γ-hydroxy carbonyl compounds from enones with carbon homologation

Abstract The alkylation of enone with 1-chloroalkyl phenyl sulfoxide followed by treatment with thiophenolate afforded α-phenylthio-β, γ-unsaturated carbonyl compound, which was oxidized and then hydrolyzed to give α, β-unsaturated γ-hydroxy carbonyl compound in good yield.

Glycosidic Inhibitors of Melanogenesis from Leaves of Passiflora edulis

A new flavonoid glycoside, chrysin 6‐C‐β‐rutinoside (chrysin α‐L‐rhamnopyranosyl‐(1→6)‐C‐β‐glucopyranoside; 2), and two new triterpene glycosides, (31R)‐31‐O‐methylpassiflorine (7) and (31S)‐31‐O‐methylpassiflorine (8), along with 14 known glycosides, including three flavonoid glycosides, 1, 3, and 4, six triterpene glycosides, 5, 6, and 9–12, three cyano glycosides, 13–15, and two other glycosides, 16 and 17, were isolated from a MeOH extract of the leaves of Passiflora edulis (passion flower; Passifloraceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. Upon evaluation of compounds 1–17 against the melanogenesis in the B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), three compounds, isoorientin (1), 2, and (6S,9R)‐roseoside (17), exhibited inhibitory effects with 37.3–47.2% reduction of melanin content with no, or almost no, toxicity to the cells (90.8–100.2% cell viability) at 100 μM. Western blot analysis showed that compound 2 reduced the protein levels of MITF, TRP‐1, and tyrosinase, in a concentration‐dependent manner while exerted almost no influence on the level of TRP‐2, suggesting that this compound inhibits melanogenesis on the α‐MSH‐stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of TRP‐1 and tyrosinase. In addition, compounds 1–17 were evaluated for their inhibitory effects against the EpsteinBarr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.

Stereochemically Controlled Asymmetric 1,2-Reduction of Enones Mediated by a Chiral Sulfoxide Moiety and a Lanthanum(III) Ion

Enantiomerically pure (Z)-β-sulfinyl allylic alcohols of either handedness can be readily prepared from (Z)-β-sulfinyl enones using NaBH(4) or DIBAL reductants in the presence of LaCl(3) as a chelating agent. A chiral sulfoxide auxiliary induces the remote 1,2-asymmetric reduction (1,4-induction) to afford various chiral allylic alcohols in high yields with excellent stereoselectivities (up to 100% de).