Geographic variation in the field response of male European pine sawflies, Neodiprion sertifer, to different pheromone stereoisomers and esters

The European pine sawfly, Neodiprion sertifer (Geoffroy) (Hymenoptera: Diprionidae), is a widespread and economically important forest insect. The sex pheromone communication system of this species has been previously investigated in North America, Japan and Europe, with the acetate or propionate of the alcohol (2S,3S,7S)-3,7-dimethyl-2-pentadecanol (diprionol) shown to be the main pheromone component. In some locations, male attraction either increased or decreased by the addition of the (2S,3R,7R)-diprionyl acetate isomer. However, these studies were made with different batches of synthetic pheromones, with different types of traps and according to different procedures, so the observed differences might not reflect true geographic variation. Here we investigate the geographic pattern of male sawfly response by using identical chemicals, traps and experimental procedures at eight field sites ranging from Japan in the east to Canada in the west. We found an increased inhibitory effect of the (2S,3R,7R)-isomer from Japan and Siberia to Europe. At the eastern sites, increasing amounts of the (2S,3R,7R)-isomer up to and equal to the amount of the (2S,3S,7S )-isomer, did not influence the trap catch, whereas at sites in Europe, as little as 1% of the (2S,3R,7R)-isomer almost completely inhibited the attraction. The response of the North American population was intermediate. The only site in which the (2S,3R,7R)-isomer was essential for the attraction of males was in Siberia. A similar pattern was found for the (2S,3R,7S)-isomer. Both the acetate and the propionate form of the (2S,3S,7S)-isomer were attractive by themselves in Japan, Europe and North America, and neither the (2S,3R,7S)-isomer nor the (2S,3R,7R)-isomer alone were attractive, in the acetate or propionate form. We discuss the significance of our findings for the development of more efficient monitoring schemes and for the causes of population divergence and speciation in the European pine sawfly.     

Syntheses of 2-Deoxy-2-[(2R,3S)-2-fluoro-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-D-glucopyranose and Its (2S,3R)-Isomer

2-Deoxy-2-[(2R,3S)-2-fluoro-3-hydroxytetradecanamido]-3-O-[(3R)-3-hydroxytetradecanoyl]-4-O-phosphono-D-glucopyranose and its (2S,3R)-isomer were respectively synthesized from allyl 2-[(2R,3S)-3-(benzyloxycarbonyloxy)-2-fluorotetradecanamido]-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside and its corresponding (2S,3R)-isomer. Both target compounds did not activate macrophage, but the (2S,3R)-analogue strongly inhibited the binding of LPS to macrophage.     

Anthranilic Acid,as a Fruiting Body Inducing Substance in Favolus arcularius,from a Strain TA 7 of Actinomycetes

The stereochemical inversion of (R)-5-hydroxymethyl-3-tert-butyl-2-oxazolidinone (la) or (R)-5-hydroxymethyl-3-isopropyl-2-oxazolidinone (lb) to the corresponding (S)-isomer was accomplished via a key intermediate, (R)-3-N-ethoxycarbonyl-N-tert-butylamino-l,2-epoxypropane (5a) or (R)-3-N-ethoxycarbonyl-N-isopropylamino-l,2-epoxypropane (5b), in a high enantiomeric excess. (S)-la (99%e.e.) or (S)-lb (91%e.e.) was thus obtained from the respective (R)-isomer (la; 99%e.e., lb; 95%e.e.).     

Evaluation of the Suppressive Effect on Bitter Taste of Gluconate

Improved conditions for the production and characterization of 1-arylpropane-1, 2-diols and related compounds were developed. Experimental conditions providing highly enhanced activity of pyruvate decarboxylase in bakers’ yeast in the presence of pyruvate, thiamine pyrophosphate, and magnesium(II) salt were applied to the preparation of (R)-1-hydroxy-1-phenyl-2-propanone from benzaldehyde. Subsequent reduction with bakers’ yeast efficiently afforded 1-phenyl-1, 2-propanediol (35%). The composition of its stereoisomers was precisely determined, and the major (1R, 2S)-isomer (89% of the total mixture) could be isolated by recrystallizing the corresponding benzoate. The analytical method for identifying the stereoisomeric composition was also effective for the determination of 5-phenyl-4-pentene-2, 3-diol, the biotransformation product from cinnamaldehyde, the vinylogous substrate of benzaldehyde. Furthermore, the structural characterization of 1-(2-furyl)propane-1, 2-diol, which was obtained from furfural (28%) by the action of brewers’ yeast Saccharomyces cerevisiae (carlsbergensis), is described. The major (1S, 2S)-isomer could be isolated by recrystallizing the crude product.     

L-Cystathionine as a Component of Ezomycins A1 and B1 from a Streptomyces

(1R,2S)-1-(3′-Chloro-4′-methoxyphenyl)-1,2- propanediol (Trametol, 3), a metabolite of the fungus Trametes sp. IVP-F640 and Bjerkandera sp. BOS55, was synthesized by employing Sharpless asymmetric dihydroxylation as the key step. Similarly, the (1R,2S)-isomer of 1-(3′,5′-dichloro-4′-methoxyphenyl)-1,2-propanediol (4), another metabolite of Bjerkandera sp. BOS55, was synthesized by asymmetric dihydroxylation.     

Substrate specificity and stereospecificity of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis DCL14; an enzyme showing sequential and enantioconvergent substrate conversion

Limonene-1,2-epoxide hydrolase (LEH) from Rhodococcus erythropolis DCL14, an enzyme involved in the limonene degradation pathway of this microlorganism, has a narrow substrate specificity. Of the compounds tested, the natural substrate, limonene-1,2-epoxide, and several alicyclic and 2-methyl-1,2-epoxides (e.g. 1-methylcyclohexene oxide and indene oxide), were substrates for the enzyme. When LEH was incubated with a diastereomeric mixture of limonene-1,2-epoxide, the sequential hydrolysis of first the (1R,2S)- and then the (1S,2R)-isomer was observed. The hydrolysis of (4R)- and (4S)-limonene-1,2-epoxide resulted in, respectively, (1S,2S,4R)- and (1R,2R,4S)-limonene-1,2-diol as the sole product with a diastereomeric excess of over 98%. With all other substrates, LEH showed moderate to low enantioselectivities (E ratios between 34 and 3).     

Heterologous expression of geraniol dehydrogenase for identifying the metabolic pathways involved in the biotransformation of citral by Acinetobacter sp. Tol 5

ABSTRACT

The biotransformation of citral, an industrially important monoterpenoid, has been extensively studied using many microbial biocatalysts. However, the metabolic pathways involved in its biotransformation are still unclear, because citral is a mixture of the trans-isomer geranial and the cis-isomer neral. Here, we applied the heterologous expression of geoA, a gene encoding geraniol dehydrogenase that specifically converts geraniol to geranial and nerol to neral, to identify the metabolic pathways involved in the biotransformation of citral. Acinetobacter sp. Tol 5 was employed in order to demonstrate the utility of this methodology. Tol 5 transformed citral to (1R,3R,4R)-1-methyl-4-(1-methylethenyl)-1,3-cyclohexanediol and geranic acid. Biotransformation of citral precursors (geraniol and nerol) by Tol 5 transformant cells expressing geoA revealed that these compounds were transformed specifically from geranial. Our methodology is expected to facilitate a better understanding of the metabolic pathways involved in the biotransformation of substrates that are unstable and include geometric isomers.     

Cloning and Expression of the Bacillus subtilis No. 313 γ-Cyclodextrin Forming CGTase Gene in Escherichia coli

All four stereoisomers of pyriculol were synthesized to assist in forming a correlation between their chemical structure and biological activity. The (R,E)-2-hydroxy-3-pentenal derivative was coupled with a lithium acetylide derivative to give a diastereomeric mixture of the acetylenic alcohol, which led to the antipode of pyriculol and its 3′-epimer. Similarly obtained were the natural pyriculol and its 3′-epimer from the (S)-isomer of this aldehyde.     

Docking based design of diastereoisomeric MTCA as GPIIb/IIIa receptor inhibitor

In GPIIb/IIIa mediated arterial thrombosis platelet activation plays a central role. To discover platelet activation inhibitor the pharmacophores of GPIIb/IIIa receptor inhibitors and anti-thrombotic agents were analyzed. This led to the design of (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids as GPIIb/IIIa inhibitors. Comparing to (1S,3S)-isomer (1R,3S)-isomer had lower cdocker interaction energy. AFM image showed that the minimal effective concentration of (1S,3S)-isomer and (1R,3S)-isomer inhibiting platelet activation were 10^?5?M and 10^?6?M, respectively. In vivo 1?μmol/kg of oral (1S,3S)-isomer effectively inhibited the rats to form arterial thrombus and down regulated GPIIb/IIIa expression, but the activities were significantly lower than those of 1?μmol/kg of oral (1R,3S)-isomer. Both (1S,3S)-isomer and (1R,3S)-isomer can be safely used for structural modifications, but (1R,3S)-isomer should be superior to (1S,3S)-isomer.     

Independent and joint action of cis- and trans-permethrin in Triatoma infestans (Hemiptera: Reduviidae)

The toxicity of pure cis- and trans-permethrin or mixtures of the two isomers topically applied to first, third, and fifth instar nymphs of Triatoma infestans (Klug) at 26°C was determined. The cis-isomer was more active than the trans-isomer in the three stages evaluated. When the two isomers were simultaneously applied to first instar nymphs, an additive effect was observed. Similar treatments of third and fifth instar nymphs resulted in an antagonistic effect. In third instar nymphs, the cis-isomer was more active than trans-isomer at all the three temperatures assayed (16°, 26°, and 36°C). The toxicity of the cis-isomer was lower at 36°C than at either 16° or 26°C. Temperature had no significant effect on the toxicity of the trans-isomer within the temperature range assayed. The toxicity of either isomer to third instar nymphs was not affected by pretreatment of nymphs with PBO (an inhibitor of mixed-function oxidases activity) or TPP (an inhibitor of esterase activity), suggesting that these detoxification pathways are not relevant in the metabolism of cis- or trans-isomers. Arch. Insect Biochem. Physiol. 37:225–230, 1998. © 1998 Wiley-Liss, Inc.     

Use of isotopically chiral [4′-13C]penciclovir and 13C NMR to determine the specificity and absolute configuration of penciclovir phosphate esters formed in HSV-1- and HSV-2-infected cells and by HSV-1-encoded thymidine kinase

Penciclovir is a potent antiherpesvirus agent which is highly selective due to its phosphorylation only in virus infected cells. Phosphorylation of one of the hydroxymethyl groups of penciclovir (PCV) creates a chiral centre leading to the possible formation of (R)- and (S)-enantiomers. The absolute configuration and stereospecificity of the PCV-phosphates produced in cells infected with herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), as well as by HSV-1-encoded thymidine kinase, were determined using isotopically chiral [4′-¹³C]PCV precursors and ¹³C NMR spectroscopy of the isolated metabolites. The absolute configuration of penciclovir-triphosphate (PCV-TP) produced in HSV-1-infected cells was shown to be S with an enantiomeric purity of greater than 95%. However, in contrast to HSV-1-infected cells in which none of the (R) enantiomer was detected, about 10% of (R)-PCV-TP was produced in HSV-2-infected cells. Phosphorylation of PCV by HSV-1-encoded thymidine kinase was found to give 75% (S)- and 25% (R)-PCV-monophosphate. The proportion of the (S)-isomer appears to be amplified in the subsequent phosphorylations leading to the triphosphate. © 1993 Wiley-Liss, Inc.     

Stereoselective esterification of halogen-containing carboxylic acids by lipase in organic solvent: effects of alcohol chain length

Summary Optical resolution of racemic carboxylic acids containing a halogen atom was attempted with stereoselective esterificatiob by Celite-adsorbed hydrolases in organic solvents. As lipase OF 360 from Candida cylindracea was found to stereoselectively esterify 2-(4-chlorophenoxy)propanoic acid, the (R)-enantiomer (d-isomer) of which is an important herbicide, the effects of alcohol chain length on stereoselectivity as well as reaction rate were investigated. The results revealed that the alcohol chain length markedly affected the stereoselective esterification of 2-(4-chlorophenoxy)propanoic acid: longer-chain alcohols, such as tetradecanol, served as excellent substrates for optical resolution of the acid, although the reaction rate was moderate. Offprint requests to: A. Tanaka     

Constitutional Studies on the Mucilage of “Yamanoimo,” Dioscorea batatas Decne,forma Tsukune

All four stereoisomers of 10,14-dimethyloctadec-1-ene, a sex pheromone component of the apple leafminer (Lyonetia prunifoliella: Lepidoptera), were synthesized starting from (R)- and (S)-propylene oxide by applying stereospecific inversion of chiral secondary tosylates as a key step. Field evaluation showed that male moths of the Japanese population were selectively attracted by the (10S,14S)-isomer and that the activity was not inhibited by the enantiomer.     

Asymmetric Hydrolysis of (±)-α-Substituted Garboxylic Acid Esters with Microorganisms

Microorganisms that hydrolyze methyl 2-phenylpropionate (1) or reduce 4-phenyl-2-butanone (3) were screened from 250 type cultures. Several Aspergilli and two bacteria hydrolyzed ester 1, and Asp. sojae IAM 2703 preferentially hydrolyzed (R)-isomer of (±)-1, whereas Bacillus subtilis var. niger IFO 3108 and Mycobacterium smegmatis ATCC 10143 preferentially hydrolyzed (S)-isomer. The hydrolysis of the related esters of 1 with these organisms was also examined.     

Chiral spin crossover iron(II) complex, fac-Λ-[Fe(HL)3](ClO4)2·EtOH (HL = 2-methylimidazol-4-yl-methylideneamino-R-(+)-1-methylphenyl)

A chiral spin crossover iron(II) complex, fac-Λ-[Fe^II(HL^R)₃](ClO₄)₂·EtOH was synthesized and its crystal structures in both the high-spin (HS) and low-spin (LS) states were determined, where HL^R denotes 2-methylimidazol-4-yl-methylideneamino-R-(+)-1-methylphenyl. The complex assumes octahedral coordination geometry of N₆ donor atoms by three bidentate ligands HL^R. The complex exists as the facial-Λ-isomer of fac-Λ-[Fe^II(HL^R)₃]²⁺ of the possible geometrical fac- and mer-isomers and the Δ- and Λ-enantiomorphs. The X-ray structural analyses revealed that the R-form of the ligand (HL^R) induces the fac-Λ-isomer of fac-Λ-[Fe^II(HL^R)₃]²⁺ and the S-form of the ligand (HL^S) induces the fac-Δ-isomer of fac-Δ-[Fe(HL^S)₃]²⁺. The complex fac-Λ-[Fe^II(HL^R)₃](ClO₄)₂·EtOH shows a complete steep spin crossover between the HS and the LS states at T_1/2 = 195 K.     

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.     

4-Hydroxyisoleucine from seed of Trigonella foenum-graecum

The principal free amino acid present in seed of Trigonella foenum-graecum has been isolated and identified as (2S, 3R, 4R)-4-hydroxyisoleucine. This compound has not been reported previously as a constituent of higher plants, but it is a component of the toxic peptide, γ-amanitin, produced by Amanita phalloides. The (2S, 3R, 4R)-isomer lactonizes readily under acidic conditions, whilst strong acid causes partial epimerization. The (2R, 3R, 4R)-isomer forms a minor component of Trigonella seed. The 4-hydroxyisoleucine content of fenugreek increases during the growth of seedlings and plants, and ¹⁴C-isoIeucine was used effectively as a biosynthetic precursor.     

Optical resolution of racemic 2-hydroxy octanoic acid by lipase-catalyzed hydrolysis in a biphasic membrane reactor

Racemic 2-hydroxy octanoic acid methyl ester was optically resolved by lipase-catalyzed hydrolysis in a biphasic membrane reactor using hydrophilic/hydrophobic capillary membranes. In a buffer/hexane biphasic membrane reactor using hydrophilic ultrafiltration membranes, (S)-2-hydroxy octanoic acid was recovered from the aqueous phase at 59–67% yield and 0.9–0.92 enantiomeric excess (ee), and the ester of (R)-isomer was recovered from the organic phase at 73–75% yield and 0.92–0.99 ee.     

A New Ribityllumazine Derivative

Lipase-catalyzed enantioselective lactonization of racemic methyl 6-phenyl-4-hydroxy-5-hexynoate worked well to afford (R)-6-phenyl-5-hexyn-4-olide (42% yield, 81% e.e.). The e.e. of the product was enhanced to 97% by the repetition of enzymatic reaction. From this lactone, (4R,5R)-isomer of 5-hydroxy-6-phenyl-4-hexanolide, a lateral root inducing substance from Erwinia quercina was synthesized via a selective epoxidation of the intermediate and subsequent hydrogenolysis as the keystep.     

Synthesis and structure–activity relationships of pyrazolodiazepine derivatives as human P2X7 receptor antagonists

Screening of library compounds has yielded pyrazolodiazepine derivatives with P2X₇ receptor antagonist activity. To explore the structure–activity relationships (SAR) of these pyrazolodiazepines as human P2X₇ receptor antagonists, derivatives were synthesized by substitutions at positions R² and R³ of the pyrazolodiazepine skeleton. Using a 2′(3′)-O-(4-benzoylbenzoyl)ATP (BzATP)-induced fluorescent ethidium uptake assay, the activities of these derivatives were tested in HEK-293 cells stably expressing human P2X₇ receptors. Moreover, the effect of these derivatives was assessed by measuring their effect on IL-1β release induced by BzATP-induced activation of differentiated THP-1 cells. A 2-phenethyl pyrazolodiazepine derivative with a 1-methyl-1H-3-indolyl group at position R² had fivefold greater activity than the derivative with a 5-isoquinolinyl at R². Moreover, a benzyl moiety at R³ had fivefold greater activity than a bicyclic moiety. The stereochemical effect at C-6 showed a preference for the (R)-isomer. Among the series of active derivatives, compound 23b, with a phenethyl group at R¹, a 3-methyl indole at R², and a benzyl at R³, exhibited activity similar to that of the positive control, KN-62, as shown by the inhibitory effects of IL-1β release.