Chemoenzymatic Preparation of Optically Active Long-Chain 3-Hydroxyalkanoates

The synthesis of optically active 3-hydroxyalkanoates of varying chain length (C_lo, C₁₄ and C₁₈) was investigated using chemoenzymatic methods. While bakers' yeast mediated reduction of 3-oxoalkanoates gave (R)-3-hydroxyalkanoates (e.e. >80%, yield —10%), both enantiomers were obtained by enzymatic resolution of racemic methyl 3-butanoyloxyalkanoates using Geotrichum candidum lipase with moderate to good optical purity (e.e. 32–92%, yield 40–60% for both enantiomers). Lipase-catalysed interesterification, however, was found to proceed with similar enantioselectivity but with slow rate of conversion.     

Stereoselective Synthesis of the Optically Active Samin Type of Lignan from L-Glutamic Acid

The optically active samin type of lignan, (1R,2S,5R, 6S)-6-(2-methoxy-4,5-methylenedioxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-2-ol, was stereoselectively synthesized from L-glutamic acid via (2R,3R)-2-[(1S and R)- 1-[(tert-butyldimethylsilyl)oxy]-1-(2-methoxy-4,5-methylenedioxyphenyl)methyl]-3-[(tert-butyldiphenylsilyl)oxy]methyl-1,4-butanediol.     

Synthesis and Insecticidal Activity of Some New Optically Active Phenylphosphonothiolates and Thionates

The four sesquiterpenes shizukanolide (1), dehydro-shizukanolide (2), glechomanolid (3) and isofuranodiene (4) were isolated from Chloranthus japonicus Sieb. (Hitori-shizuka in Japanese, Chloranthaceae). Their absolute structures have been established on the basis of their physical and chemical properties. Dehydro-shizukanolide showed moderate antifungal activity.     

Microbial Resolution of 2-Hydroxy-3-nitropropionic Acid for Synthesis of Optically Active Isoserine

The biocatalytic stereoselective hydrolysis of 2-hydroxy-3-nitropropionic acid esters was studied. Forty enzymes and three hundred microorganism strains were examined for their ability to hydrolyze ethyl 2-hydroxy-3-nitropropionic acid. Nocardia globerula IFO13150 gave n-butyl (R)-2-hydroxy-3-nitropropionate with a 92% enantiomeric excess (ee) and the corresponding carboxylic acid with a 92%ee, which was easily converted to (S)-isoserine, a useful β-amino acid.     

Novel Synthesis of Optically Active Bishomotyrosine Derivatives Using the Friedel-Crafts Reaction in Triflic Acid

We report here a novel synthesis of optically active bishomotyrosine. The bishomotyrosine skeleton was constructed by using a Friedel-Crafts reaction between phenol and optically active N-Tfa-Glu(Cl)-OMe in triflic acid under the mild condition. Reduction and subsequent deprotection then afforded bishomotyrosine derivatives without any loss of optical purity.     

光学活性叔亮氨酸合成的研究进展

由于叔丁基的特殊结构和性质 ,叔亮氨酸是重要的医药中间体和不对称合成的手性诱导模板。本文综述了近年来光学活性的叔亮氨酸的合成研究及最新进展。     

New Synthesis of Optically Active O-Aryl O-Ethyl Phenylphosphonothionates

The mixed anhydride method was applied to synthesize O-aryl O-ethyl phenylphosphonothionate. The reaction of O, O-diethyl phosphorochloridate with O-ethyl phenylphosphonothioic acid afforded O, O-diethyl phosphoric O-ethyl phenylphosphonothioic anhydride in a good yield. This anhydride was converted to O-aryl O-ethyl phenylphosphonothionates by reacting with the appropriate sodium phenoxide. This esterification occurred without racemization and produced optically pure O-ethyl O-(4-nitrophenyl) phenylphosphonothionate (EPN) and O-(4-cyanophenyl) O-ethyl phenylphosphonothionate (cyanofenphos).     

Stereoselective Model Synthesis of the Optically Active Olivil Type of Lignan from D-Xylose

The olivil type of lignan, (2S,3R,4R)-4-benzyl-4- hydroxy-3-hydroxymethyl-2-(3,4-methylenedioxyphenyl)tetrahydrofuran, was stereoselectively synthesized from D-xylose.     

Microbial Production of Optically Active 1,3-Butanediol from 4-Hydroxy-2-butanone

The effect of insulin on polypeptide chain elongation was examined in soleus muscles isolated from 18 hour-fasted mice. Treatment with insulin for 1 hour increased the elongation rate, which was estimated by the half-transit time. This suggests that insulin stimulated protein synthesis by modifying the elongation rate in addition to the initiation rate.     

Optically Active Compounds Derived from Salicylaldehyde and Pyridoxal: Syntheses and Their Chelate Formation Properties in the Interaction with α-Amino Acid

Synthesis of chiral compounds derived from salicylaldehyde and pyridoxal was carried out. In aqueous media containing copper ion, these compounds were analyzed to form Schiff base copper chelate spontaneously with α-amino acid. This complex formation process was reversed by the addition of EDTA. Applicabilities of the compounds to the resolution of α-amino acids are discussed.     

Brain Synthesis and Cerebrovascular Action of Epoxygenase Metabolites of Arachidonic Acid

The purpose of this study was to determine if whole brain makes epoxygenase metabolites of arachidonic acid and, if so, whether they are vasoactive on the cerebral microcirculation. Blood-free mouse brain slices were incubated with exogenous radiolabeled arachidonic acid, and the extracted metabolites were resolved by HPLC. Metabolite structures were confirmed by gas chromatography/mass spectrometry. In addition to prostaglandins, leukotriene B4, and hydroxyeicosatetraenoic acids, mouse brain metabolized arachidonic acid into several other compounds. Among them, we identified 5,6- and 14,15-epoxyeicosatrienoic acid. Next, we tested the effect of topical application of brain-synthesized 5,6-epoxyeicosatrienoic acid and synthetic epoxyeicosatrienoic acids on in vivo rabbit cerebral arteriolar diameter using the cranial window technique and in vivo microscopy. Brain-synthesized 5,6-epoxyeicosatrienoic acid caused a transient 28% arteriolar dilation, similar to that produced by 5 micrograms/ml of synthetic 5,6-epoxyeicosatrienoic acid. A concentration of synthetic 14,15- and 11,12-epoxyeicosatrienoic acid of 5 micrograms/ml CSF had little or no effect on diameter, whereas 8,9-epoxyeicosatrienoic acid caused a maximum dilation of 8%. These studies suggest that brain-synthesized 5,6-epoxyeicosatrienoic acid may play a role in the normal or pathophysiological regulation of the cerebral microcirculation.     

The design, synthesis, and evaluation of novel conformationally rigid analogues of sialyl Lewis

The design and synthesis of a series of analogues of sialyl Lewis^x (1) which incorporate conformationally rigid tetralin and naphthalene ring systems (2–4) has led to novel compounds which have similar potency to 1 as inhibitors of cell adhesion.     

Preparation of Optically Active 2-Aminobutanoic Acid via Optical Resolution by Replacing Crystallization

An attempt was made to use a simple procedure to obtain (R)- and (S)-2-aminobutanoic acids [(R)- and (S)-1] which are non-proteinogenic α-amino acids and are useful as chiral reagents in asymmetric syntheses. Compound (RS)-1 p-toluenesulfonate [(RS)-2], which is known to exist as a conglomerate, was optically resolved by replacing crystallization with (R)- and (S)-methionine p-toluenesulfonate [(R)- and (S)-3] as optically active co-solutes. When (S)-3 was employed as the co-solute, (R)-2 was preferentially crystallized from a supersaturated solution of (RS)-2 in 1-propanol, as was (S)-2 in the presence of (R)-3. (R)- and (S)-2 recrystallized from 1-propanol were treated with triethylamine in methanol to give (R)- and (S)-1 in optically pure forms.     

毛霉菌油对被孢霉产花生四烯酸的影响

研究了不同浓度毛霉菌油对被孢霉产花生四烯酸（AA）的影响,发现0.3%毛霉菌油可以显著提高花生四烯酸产量,并研究了0.3%毛霉菌油在整个发酵过程中对被孢霉产花生四烯酸的影响。结果表明,毛霉菌油对被孢霉生长和油脂产量基本上没有影响,毛霉菌油可以提高被孢霉的AA产量,主要是因为其能提高AA在油脂中的含量。     

云南脂松香制备光学纯去氢枞酸的研究

以松节油作反应溶剂,在硫、碘的催化作用下云南脂松香经催化异构化、脱氢成为脱氢松香酸,通过进一步的提取、纯化等步骤可直接得到纯度高达96%以上的光学纯的去氢枞酸,其收率为26.6g/100g(松香)。     

Growth-Coupled Lipid Synthesis in Mortierella alpina LPM 301, a Producer of Arachidonic Acid

Mortierella alpina LPM 301, a producer of arachidonic acid (ARA), was found to possess a unique property of intense lipid synthesis in the period of active mycelium growth. Under batch cultivation of this strain in glucose-containing media with potassium nitrate or urea, the bulk of lipids (28–35% of dry biomass) was produced at the end of the exponential growth phase and remained almost unaltered in the stationary phase. The ARA content of lipids comprised 42–50% at the beginning of the stationary phase and increased continuously after glucose depletion in the medium due to the turnover of intracellular fatty acids; by the end of fermentation (189–210 h), the amount of ARA reached 46–60% of the total fatty acids (16–19% of dry mycelium). Plausible regulatory mechanisms of the growth-coupled lipid synthesis in microorganisms are discussed.     

Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer

The carbohydrate determinants, sialyl Lewis A and sialyl Lewis X, which are frequently expressed on human cancer cells, serve as ligands for a cell adhesion molecule of the selectin family, E-selectin, which is expressed on vascular endothelial cells. These carbohydrate determinants are involved in the adhesion of cancer cells to vascular endothelium and thus contribute to hematogenous metastasis of cancer. The initial adhesion mediated by these molecules triggers activation of integrin molecules through the action of several cytokines and leads to the extravasation of cancer cells. Cancer cells also produce humoral factors that facilitate E-selectin expression on endothelial cells. The degree of expression of the carbohydrate ligands at the surface of cancer cells is well correlated with the frequency of hematogenous metastasis and prognostic outcome of patients with cancers. The alteration of glycosyltransferase activities that leads to the enhanced expression of these carbohydrate ligands on cancer cell surface are currently being investigated. This revised version was published online in November 2006 with corrections to the Cover Date.     

The role of the cytoskeleton in cellular adhesion molecule expression in tumor necrosis factor-stimulated endothelial cells

Leukocyte infiltration is a hallmark of the atherosclerotic lesion. These cells are captured by cellular adhesion molecules (CAMs), including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cell adhesion molecule (PECAM), and E-selectin, on endothelial cells (EC). We examined the role of the actin cytoskeleton in tumor necrosis factor-alpha (TNF-alpha)-induced translocation of CAMs to the cell surface. Human aortic EC were grown on 96-well plates and an ELISA was used to assess surface expression of the CAMs. TNF-alpha increased VCAM-1, ICAM-1, and E-selectin by 4 h but had no affect on the expression of PECAM. A functioning actin cytoskeleton was important for VCAM-1 and ICAM-1 expression as both cytochalasin D, an actin filament disruptor, and jasplakinolide, an actin filament stabilizer, attenuated the expression of these CAMs. These compounds were ineffective in altering E-selectin surface expression. Myosin light chains are phosphorylated in response to TNF-alpha and this appears to be regulated by Rho kinase instead of myosin light chain kinase. However, the Rho kinase inhibitor, Y27632, had no affect on TNF-alpha-induced CAM expression. ML-7, a myosin light chain kinase inhibitor, had a modest inhibitory effect on the translocation of VCAM-1 but not on ICAM-1 or E-selectin. These data suggest that the surface expression of VCAM-1 and ICAM-1 is dependent on cycling of the actin cytoskeleton. Nevertheless, modulation of actin filaments via myosin light chain phosphorylation is not necessary. The regulation of E-selectin surface expression differs from that of the other CAMs.     

Effects of Arachidonic Acid on Dopamine Synthesis, Spontaneous Release, and Uptake in Striatal Synaptosomes from the Rat

Abstract: Arachidonic acid (AA) markedly stimulated, in a dose-dependent manner, the spontaneous release of [³H]dopamine ([³H]DA) continuously synthesized from [³H]tyrosine in purified synaptosomes from the rat striatum. As estimated by simultaneous measurement of the rate of [³H]H₂O formation (an index of [³H]tyrosine conversion into [³H]DOPA), the AA response was associated with a progressive and dose-dependent reduction of [³H]DA synthesis. In contrast to AA, arachidic acid, oleic acid, and the methyl ester of AA (all at 10⁻⁴ M ) did not modify [³H]DA release. The AA (3 × 10⁻⁵ M )-evoked release of [³H]DA was not affected by inhibiting AA metabolism, with either 5,8,11,14-eicosatetraynoic acid or metyrapone, suggesting that AA acts directly and not through one of its metabolites. AA also inhibited in a dose-dependent manner [³H]DA uptake into synaptosomes, with a complete blockade observed at 10⁻⁴ M . However, AA (10⁻⁴ M ) still stimulated [³H]DA spontaneous release in the presence of either nomifensine or other DA uptake inhibitors, indicating that AA both inhibits DA reuptake and facilitates its release process. Finally, the AA (10⁻⁴ M )-evoked release of [³H]DA was not affected by protein kinase A inhibitors (H-89 or Rp -8-Br-cAMPS) but was markedly reduced in the presence of protein kinase C inhibitors (Ro 31-7549 or chelerythrine).     

Cyclothiazide Unmasks an AMPA-Evoked Release of Arachidonic Acid from Cultured Striatal Neurones

Abstract: The joint, but not independent, activation of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and metabotropic glutamate receptors induces liberation of arachidonic acid from cultured mouse striatal neurones. We examined whether blocking AMPA receptor desensitisation with cyclothiazide would modify this response. Cyclothiazide strongly potentiated the combined AMPA/(1 S ,3 R )-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD)-evoked release of arachidonic acid (EC₅₀ of ∼7 µ M ) but did not modulate the basal, ACPD, or NMDA response. The enhanced liberation of arachidonic acid, observed in the presence of cyclothiazide, was due to the appearance of a genuine AMPA response that was independent of an associative activation of metabotropic receptors. The potentiated and nonpotentiated AMPA responses were inhibited by both competitive [2,3-dihydroxy-6-nitro-7-sulphamoylbenzo( f )quinoxaline] and 2,3-benzodiazepine noncompetitive (GYKI 53655 and GYKI 52466) receptor antagonists. Cyclothiazide was equally effective at potentiating the AMPA response in either the presence or absence of glucose, suggesting that the increased glutamate-evoked arachidonic acid release observed in these cells under conditions of glucose deprivation is not due to reduced AMPA receptor desensitisation. The enhanced liberation of arachidonic acid measured in the presence of cyclothiazide appeared to result from a large (fourfold) elevation of the AMPA-induced increase in intracellular calcium level. Therefore, an AMPA-evoked mobilisation of arachidonic acid could potentially contribute to non-NMDA receptor-mediated neurotoxicity, which has been observed in neuronal cells in the presence of cyclothiazide.