Field response of the pine sawfly Neodiprion sertifer to the pheromone (2S,3S,7S)-diprionyl acetate and its stereoisomers

All eight optical isomers of 3,7-dimethyl-2-pentadecanyl acetate (diprionyl acetate), of high optical purity (> 97.4%), were tested for a behavioural activity on male pine sawflies, Neodiprion sertifer (Geoffr.) (Hymenoptera: Diprionidae), in northern Europe. Males were strongly attracted to (2S,3S,7S)-diprionyl acetate. Addition of more than 0.1% of the (2S,3R,7R)-isomer reduced the catch and above 2% the attraction was completely inhibited. Contrary to what has been reported for North American and Japanese populations, so significant synergistic effect of small amounts of the (2S,3R,7R)-isomer could be demonstrated. The effects of addition of the other six optical isomers alone or in combinations, were also studied, but none was found to be a synergist. The (2S,3R,7S)-isomer had a weak inhibitory effect, and completely inhibited the attraction to the (2S,3S,7S)-isomer when applied in about equal amounts as the attractant. In some cases a reduction in catch was noted when other isomers were tested, but this could be attributed to the very small amounts of the inhibitory (2S,3R,7R)-isomer present in these isomers.     

(5Z, 7E)-5,7-Dodecadien-1-ol: Female Sex Pheromone of the Pine Moth Dendrolimus spectabilis Butler

The sex pheromone of the pine moth Dendrolimus spectabilis Butler was tentatively identified as 5,7-dodecadien-l-ol by the use of the electroantennogram technique. Analyses of abdominal tip extracts of virgin females by gas-liquid chromatography and mass spectroscopy showed the presence of a (5Z, 7E)-isomer and a (5E, 7E)-isomer in the ratio of about ca. 5:1. In field examinations with four synthetic isomers of 5,7-dodecadien-l-ol, only traps baited with the (5Z, 7E)-isomer captured an appreciable numbers of male moths.     

Rac-Flurbiprofen is more ulcerogenic than its (S)-enantiomer

The most common, and sometimes life-threatening, side-effects associated with the human use of the analgesic, nonsteroidal antiinflammatory drugs (NSAIDs) are gastrointestinal. These include gastritis, ulceration, and severe bleeding. The aryl propionic acid class of NSAIDs are among the most widely used of these drugs in the world, including rac-ibuprofen, rac-flurbiprofen, and rac-ketoprofen. Marketed as racemates, it was assumed that the “inactive” (R)-enantiomers, having no cyclooxygenase inhibiting effect, also had no toxic effect. In a 30-day dose response study of (S)-, (R)-, and rac-flurbiprofen given daily over a range of doses the (R)-isomer alone proved to be without apparent gastrointestinal (GI) toxicity. On the other hand the racemate proved to be 2 to 4 times as ulcerogenic in enantiomerically equivalent doses as the (S)-enantiomer. These results have significant clinical implications. © 1993 Wiley-Liss, Inc.     

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.     

A Convenient Synthesis of a Mixture of (Z,Z)-3,13-Octadecadienyl Acetate and Its (E,Z)-Isomer,the Attractant for the Cherrytree Borer

A 1:1 mixture of (Z, Z)-3,13-octadecadien-1-ol and its (E, Z)-isomer was synthesized by a Wittig reaction whose stereoselectivity was adjusted to give the products in the required ratio. The corresponding acetate mixture is useful as the attractant for Synanthedon hector.     

Synthesis and properties of (R)-2-hydroxyglutaryl-1-CoA. (R)-2-hydroxyglutaryl-5-CoA, an erroneous product of glutaconate CoA-transferase

1) (R)-2-Hydroxyglutaryl-1-CoA was synthesised starting from (R)-5-oxotetrahydrofuran-2-carboxylic acid (gamma-lactone of (R)-2-hydroxyglutarate) which was converted to the acylchloride and condensed with N-capryloylcysteamine. The lactone ring of the resulting thiolester was opened by acid hydrolysis and the CoA derivative was obtained by transesterification. 2) Pure glutaconate CoA-transferase from Acidaminococcus fermentans catalysed the formation of the 1- and the 5-isomer of (R)-2-hydroxyglutaryl-CoA from acetyl-CoA and (R)-2-hydroxyglutarate. The isomers were separated by HPLC and characterised by their reaction with acetate under the catalysis of the CoA-transferase. V/Km for the 1-isomer was 80 times higher than that for the 5-isomer. 3) Studies with cell-free extracts from A. fermentans showed that only (R)-2-hydroxyglutaryl-1-CoA but not its 5-isomer was dehydrated to glutaconyl-1-CoA. The data indicate that (R)-2-hydroxyglutaryl-5-CoA is an erroneous product of glutaconate CoA-transferase which only occurs in vitro.     

Synthesis of 9-(2-Hydroxyethoxymethyl)guanine (Acyclovir) from Guanosine

Abstract

A convenient synthesis of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) from guanosine by chemical transpurination was developed. The isomerization of the 7-isomer to the desired 9-isomer and the purification of the 9-isomer was achieved simply by concentration, heating and further crystallization.     

Inheritance of powdery mildew (Erysiphe polygoni DC) resistance in mungbean (Vigna radiata L. Wilczek)

Detached mungbean (Vigna radiata L.Wilczek) leaves were inoculated with a conidial suspension of a local isolate (TI-1) of the powdery mildew pathogen (Erysiphe polygoni DC) under controlled environment conditions. Based on the latent period and severity of the infection, a rating scale of 0–5 was used to classify the host pathogen interactions. Reactions 0, 1 and 2 were considered resistant and referred to as R0, R1 and R2 while 3, 4 and 5 were classified as susceptible (S). RUM lines (resistant to powdery mildew) and their derivatives are crossed with several susceptible (reaction types 3–5) genotypes and the inheritance of the resistance was studied in the F₁, F₂ and F₃ generations. The results showed that powdery mildew resistance in mungbean is governed by two dominant genes designated as Pm-1 and Pm-2. When both Pm-1 and Pm-2 were present, an R0 reaction was observed after inoculation with TI-1. The resistant reaction was R1 when only Pm-1 was present and R2 in the presence of Pm-2. In the absence of both Pm-1 and Pm-2, susceptible reactions 3, 4 and 5 were observed.     

Microbial synthesis of (R)- and (S)-3,4-dimethoxyamphetamines through stereoselective transamination

Two soil isolates, Arthrobacter sp. KNK168 and Pseudomonas sp. KNK425, aminated 3,4-dimethoxyphenylacetone in presence of sec-butylamine as an amino donor to yield 3,4-dimethoxyamphetamine (DMA) with different enantioselectivities. The former gave (R)-DMA (>99% e.e.) and the latter the (S)-isomer (>99% e.e.).     

Isolation and Identification of Endogenous Cytokinins from Alfalfa (Medicago sativa L)

Endogenous cytokinins in alfalfa were isolated, and identified by mass spectrometry, trans- Ribosylzeatin (RZ) and ribosyldihydrozeatin (DHRZ) were identified from the root, and the combined content (benzyladenine equivalent) was estimated to be approximately 0.5/μg/100 g of fresh weight, eis- and trans-KL were identified from the stems and leaves. The relative content of the m-isomer was approximately five times greater than that of the trans-isomer.     

Potent inhibition of thrombin by the newly synthesized arginine derivative No. 805. The importance of stereo-structure of its hydrophobic carboxamide portion

Four stereoisomers of 4-methyl-1-[N²-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid were synthesized and examined for the inhibitory effect on thrombin. The inhibitory potency varied largely with the stereo-configuration of the 4-methyl-2-piperidinecarboxylic acid portion. The (2R, 4R)-isomer was the most potent inhibitor with a Ki of 0.019 μM, while the (2R, 4S) and (2S, 4R)-isomers showed the values of Ki 0.24 and 1.9 μM, respectively. The least potent inhibitor, (2S, 4S)-isomer, showed a Ki of 280 μM which is approximately 15,000 times that of (2R, 4R)-isomer.     

Influence of Guidelines and Passageways on Tunneling Behavior of Reticulitermes flavipes (Kollar) and R. virginicus (Banks) (Isoptera: Rhinotermitidae)

Tunneling behavior of laboratory-maintained cultures of Reticulitermes flavipes (Kollar) and R. virginicus (Banks) was examined to determine (1) if the termites build tunnels along preexisting wires or tunnels, and (2) whether tunnels are arranged to optimize search efficiency. Tunnel patterns were considered optimal if, for the number of tunnels present, the maximum area was explored. Termites entered either control arenas or arenas in which they encountered a wire or a pre-formed tunnel. Analyses revealed that R. flavipes and R. virginicus almost always follow pre-formed tunnels, but do not follow wires as readily. Within each species, the distributions of tunnels in treatment arenas were different from distributions in control arenas, most often when pre-formed tunnels were the treatment. Optimal tunnel arrangements in control arenas were found in 62% of R. flavipes patterns with 2 tunnels and in 43% of R. virginicus patterns with 2 tunnels. None of the 3-tunnel patterns from control arenas of R. flavipes and 29% of those of R. virginicus had optimal arrangements. Overall, the spatial arrangement of tunnels in control arenas was significantly different between R. flavipes and R. virginicus.     

Stereoselectivity in Metabolism of the Optical Isomers of Cyanofenphos (O-p-Cyanophenyl O-Ethyl Phenylphosphonothioate) in Rats and Liver Microsomes

The racemic, (+)- and (—)-forms of cyanofenphos (O-p-cyanophenyl O-ethyl phenylphosphonothioate) were rapidly metabolized in the rat by cleavage of P-O-aryl linkage, cleavage of P-O-alkyl linkage and conjugation of p-cyanophenol with sulfuric acid. There was a marked difference in the proportion of the major urinary metabolites, p-cyanophenol and p-cyanophenyl sulfate, with three forms of cyanofenphos,

The three forms of cyanofenphos were metabolized at almost equal rates in rat liver microsomes-NADPH system. (+)-Cyanofenphos underwent oxidation of P=S to P = O and cleavage of P-O-aryl linkage predominantly. In contrast, the (?)-isomer was converted to the corresponding oxon analog by mixed function oxidase, and then the oxon analog was rapidly hydrolyzed to p-cyanophenol by mícrosomaî arylesterase-type enzyme. This microsomal enzyme had a remarkable selectivity in hydrolyzing (?)-cyanofenphos oxon versus the ( + )-isomer. Stereoselectivity in the metabolism of the cyanofenphos isomers in the rat appears likely to be mainly due to selective hydrolysis of the (?)-oxon analog by the arylesterase-type enzyme.     

Isolation and Photoisomerization of a New Anthraquinone from Hairy Root Cultures of Sesamum indicum

An unstable anthraquinone was isolated from hairy root cultures of Sesamum indicum after preventing light throughout all experimental procedures. The structure of the (Z)-isomer of a previously isolated anthraquinone was determined to be 2-[(Z)-4-methylpenta-1,3-dien-1-yl]anthraquinone by spectroscopic methods. This compound was readily isomerized to the known (E)-isomer under light.     

Enantiomeric Specificity of Biologically Significant Cu(II) and Zn(II) Chromone Complexes Towards DNA

Novel chiral Schiff base ligands (R)/(S)‐2‐amino‐3‐(((1‐hydroxypropan‐2‐yl)imino)methyl)‐4H‐chromen‐4‐one (L₁ and L₂) derived from 2‐amino‐3‐formylchromone and (R/S)‐2‐amino‐1‐propanol and their Cu(II)/Zn(II) complexes ( R1 , S1 , R2 , and S2 ) were synthesized. The complexes were characterized by elemental analysis, infrared (IR), hydrogen (¹H) and carbon (¹³C) nuclear magnetic resonance (NMR), electrospray ionization‐mass spectra (ESI‐MS), and molar conductance measurements. The DNA binding studies of the complexes with calf thymus were carried out by employing different biophysical methods and molecular docking studies that revealed that complexes R1 and S1 prefers the guanine–cytosine‐rich region, whereas R2 and S2 prefers the adenine–thymine residues in the major groove of DNA. The relative trend in K_b values followed the order R1 S1 R2 S2 . This observation together with the findings of circular dichroic and fluorescence studies revealed maximal potential of (R)‐enantiomeric form of complexes to bind DNA. Furthermore, the absorption studies with mononucleotides were also monitored to examine the base‐specific interactions of the complexes that revealed a higher propensity of Cu(II) complexes for guanosine‐5′‐monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine‐5′‐monophosphate disodium salt. The cleavage activity of R1 and R2 with pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage ability. Topoisomerase II inhibitory activity of complex R1 revealed that the complex inhibits topoisomerase II catalytic activity at a very low concentration (25 μM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin. Chirality 24:977–986, 2012. © 2012 Wiley Periodicals, Inc.     

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.     

Design and synthesis of rho kinase inhibitors (III)

The structure-activity relationship of Rho kinase inhibitors bearing an isoquinoline scaffold was studied. N-(1-Benzyl-3-pyrrolidyl)-N-(5-isoquinolyl)amine analogues were optimized with respect to their inhibitory potencies for the enzyme and for chemotaxis. The potent analogues were further evaluated by an ex vivo test in which the selected compounds were orally administered to rats, and the Rho kinase inhibitory potency observed in the rat serum was evaluated 3h after the administration. Compound 23g showed a high level of Rho kinase inhibitory activity in the rat serum and was stable in an in vitro metabolic test using a microsomal cytochrome preparation. The (R)-isomer of 23g displayed a higher level of inhibitory potency than the (S)-isomer in a cell-free kinase assay and in the cell migration assay (IC(50)(ENZ)=25 nM and IC(50)(MCP)=1 microM). The (R)-isomer successfully inhibited the phosphorylation of MBS (myosin-binding subunit) in cells.     

Binding study of semotiadil and levosemotiadil with alpha(1)-acid glycoprotein using high-performance frontal analysis.

High-performance frontal analysis (HPFA) was used to investigate the binding properties of human alpha(1)-acid glycoprotein (AGP) with semotiadil ((R)-isomer, Ca-channel blocker) and its antipode levosemotiadil ((S)-isomer, Ca- and Na-channel blockers). An on-line HPLC system consisting of a HPFA column, an extraction column, and an analytical HPLC column was used to determine the unbound concentrations of these enantiomers, and the experimental data were subsequently subjected to the Scatchard analyses to estimate their binding parameters. The binding affinity of the (R)-isomer (K = 3.17 x 10(7) M, n = 0.74) is approximately 1.2 times stronger than that of (S)-isomer (K = 2.59 x 10(7) M, n = 0.74). An enantioselective competitive binding study indicated that both enantiomers are bound at the same site on AGP molecules.     

Stereoselective synthesis of (22R)- and (22S)-castasterone/ponasterone A hybrid compounds and evaluation of their molting hormone activity

Two stereoisomers of a castasterone/ponasterone A hybrid compound, the (20R,22R) and (20R,22S)-isomers of 2alpha,3alpha,20,22-tetrahydroxy-5alpha-cholestan-6-one, were synthesized stereoselectively and their binding activity to the ecdysteroid receptor was determined. From the concentration-response curve for the inhibition of the incorporation of tritiated ponasterone A into ecdysteroid receptor containing insect cells, the concentration (IC50) required to inhibit 50% of the incorporation of radioactivity into cells was evaluated. The IC50 values of the (22R)- and (22S)-isomers were determined to be 0.30 and 38.9 microM against Kc cells, respectively, indicating that the (22R)-isomer is about 100 times more potent than the corresponding (22S)-isomer. IC50 values of these compounds against lepidopteran Sf-9 cells were determined to be 0.36 and 12.9 microM, respectively. The molting hormonal effect was examined in a Chilo suppressalis integument system and the 50% effective concentration for the stimulation of N-acetylglucosamine incorporation into the cultured integument was determined to be 2.7 microM for the (22R)-isomer, while the (22S)-isomer was inactive. On the other hand, both isomers did not show brassinolide-like activity in the rice lamina inclination assay.     

Synthesis of (+)-(R)- and (−)-(S)-trans-8-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)] aminotetralin: New 5-HT1A receptor ligands

(R,S)-trans-8-Hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)amino]tetralin 7 , a new radioiodinated ligand based on 8-OH-DPAT, was reported as a potential ligand for 5-HT_1A receptors. The optically active (+)-(R)- and (?)-(S)- 7 were prepared to investigate the stereoselectivity of (R,S)- 7 . Racemic intermediate 8-methoxy-2-N-n-propyltetralin was reacted with the acyl chloride of (?)-(R)-O-methylmandelic acid to form a mixture of (S,R)- and (R,R)-diastereoisomers, which were separated by flash column chromatography. After removing the N-acyl group from the diastereoisomers, the desired (+)-(R)-or (?)-(S)- 7 was obtained by adding an N-iodopropenyl group. In vitro homogenate binding studies showed the stereoselectivity of this new compound for 5-HT_1A receptors. (+)-(R)- 7 isomer displayed 100-fold higher affinity than the (?)-(S)- 7 isomer. Biochemical study indicated that (+)-(R)- 7 potently inhibited forskolin-stimulated adenylyl cyclase activity in hippocampal membranes (E_max and EC₅₀ were 24.5% and 5.4 nM, respectively), while (?)-(S)- 7 showed no effect at 1 μM. The radioiodinated (+)-(R)- and (?)-(S)-[¹²⁵I] 7 were confirmed by coelution with the resolved unlabeled compound on HPLC (reverse phase column PRP-1, acetonitrile/pH 7.0 buffer, 80/20). The active isomer, (+)-(R)-[¹²⁵I] 7 , displayed high binding affinity to 5-HT_1A receptors (K_d = 0.09 ± 0.02 nM). In contrast, the (?)-(S)- 7 isomer displayed a significantly lower affinity to the 5-HT_1A receptor (K_d > 10 nM). Thus, (+)-(R)-[¹²⁵I]trans-8-OH-PIPAT, (+)-(R)- 7 , an iodinated stereoselective 5-HT_1A receptor agonist, is potentially useful for study of in vivo and in vitro function and pharmacology of 5-HT_1A receptors in the central nervous system. © 1995 Wiley-Liss, Inc.