Synthesis and Biological Activities of Novel (Z)-/(E)-Anisaldehyde-Based Oxime Ester Compounds

In search of novel natural product-based bioactive molecules, twenty (ten pairs) novel (Z)-/(E)-anisaldehyde-based oxime ester compounds were designed and synthesized by using anisaldehyde as starting material. Structural characterization of the target compounds was carried out by NMR, FT-IR, ESI-MS, and elemental analysis. Their herbicidal and antifungal activities were preliminarily tested. As a result, at 50 μg/mL, compound (E)- 5b exhibited excellent to good inhibition rates of 92.3 %, 79.2 %, and 73.9 %, against Rhizoctonia solani, Fusarium oxysporum f. sp. cucumerinum, and Bipolaris maydis, respectively, better than or comparable to that of the positive control chlorothalonil. In addition, at 100 μg/mL, compounds (E)- 5b , (E)- 5f , (Z)- 5f and (E)- 5d exhibited excellent to good inhibition rates of 85.8 %, 82.9 %, 78.6 % and 64.2 %, respectively, against the root-growth of rape (B. campestris), much better than that of the positive control flumioxazin. The bioassay result also showed that the synthesized compounds had obvious differences in antifungal and herbicidal activities between (Z)- and (E)-isomers. Preliminary structure–activity relationship was also discussed by theoretical calculation.     

Generation of (2-Nitroethyl)benzene and related benzenoids from L-Phenylalanine; flower scents of the Japanese Loquat Eriobotrya japonica [Rosales: Rosaceae]

ABSTRACT

(2-Nitroethyl)benzene, methyl 4-methoxybenzoate and 4-methoxybenzaldehyde have been known as major scent components in flowers of the Japanese loquat Eriobotrya japonica [Rosales: rosaceae], together with 13 related benzenoids, including Z- and E-2-phenylacetaldoxime and benzyl alcohol. The scents air-trapped from a flowering panicle during 24 h incubation with d₈-L-phenylalanine were composed of 15 deuterium labeled compounds {d₆-styrene, d₅-benzaldehyde, d₇-2-phenylacetaldehyde, methyl d₅-benzoate, d_{7 ?}2-phenylethanol, d₇-2-phenylacetonitrile, d₄-1,4-dimethoxybenzene, d₇-Z-2-phenylacetaldoxime, d₄-4-methoxybenzaldehyde, d₇-E-2-phenylacetaldoxime, d₄-4-methoxybenzyl alcohol, d₇-(2-nitroethyl)benzene, methyl d₄-4-methoxybenzoate, methyl d₆-cinnamate and ethyl d₄-4-methoxybenzoate}. On the other hand, hexane extracts of the flower petal incubate with a mixture of d₅-Z- and d₅-E-2-phenylacetaldoxime after 24 h indicated generation of six d₅-labeld components {d₅-benzaldehyde, d₅-benzyl alcohol, d₅-2-phenylacetaldehyde, methyl d₅-benzoate, d₅-2-phenylethanol, and d₅-(2-nitroethyl)benzene}. By comparing those results, (2-nitroethyl)benzene was concluded as a product directly generated from a mixture of Z- and E-2-phenylacetaldoxime together with six minor benzenoids, while two major compounds (4-methoxybenzaldehyde and methyl 4-methoxybenzoate) together with three minors from L-phenylalanine, presumably via L-tyrosine. The other two minor components were derived from L-phenylalanine.     

Chemical Synthesis of Human β-Defensin (hBD)-1, -2, -3 and -4: Optimization of the Oxidative Folding Reaction

Reduced human β-defensin (hBD)-1, -2, -3 and -4 synthesized by Boc chemistry were subjected to oxidative folding reaction under optimal conditions. Among the factors affecting the oxidative folding in the presence of reduced and oxidized glutathione (GSH/GSSG), the buffer concentration and reaction temperature were essential for the predominant formation of the native disulfide structure. The homogeneity of the four synthetic hBDs was confirmed by analytical procedures using RP-HPLC, IEX-HPLC, capillary zone electrophoresis (CZE) and MALDI-TOF MS as well as sequencing, although high temperature (70 °C) was used for the RP-HPLC analysis of hBD-3 and hBD-4 to exclude the influence of equilibrium with the respective conformers having native disulfide pairing. All synthetic hBDs were shown to possess the native disulfide structure by sequential analyses and mass measurements with cystine segments obtained by enzymatic digestion. Upon digestion of hBD-1 and hBD-4 with proline specific endopeptidase, the Cys-X bond was found to be reproducibly cleaved together with the Pro-X bond although the cleavage of Cys-X afforded the appropriate cystine segments for determining the disulfide structure of hBD-1 and hBD-4. With respect to antimicrobial activity against E. coli, the four synthetic hBDs of high homogeneity possessed the same potencies as those reported previously.Australian Peptide Conference Issue     

Synthesis of (3E, 5Z)-3,5-Dodecadienylacetate,the Sex Pheromone of Phtheochroa cranaodes (Lepidoptera: Tortricidae)

(3E, 5Z)-3,5-Dodecadienyl acetate, the female sex pheromone of Phtheochroa cranaodes, was regio and stereo-selectively synthesized from 1-octyne and (E)-4-bromo-3-buten-1-ol by using Pd(PPh₃)₄, CuI and piperidine to afford the enyne (5). Further elaboration afforded the target pheromone. The synthetic pheromone was identified with the natural product by its MS and IR, data GLC retention time and biological activity.     

Sex pheromone biosynthesis in the Asian corn borer Ostrinia furnacalis (II): Biosynthesis of (E)- and (Z)-12-tetradecenyl acetate involves Δ14 desaturation

Sex pheromone biosynthesis in the Asian corn borer Ostrinia furnacalis was studied by topical application of deuterium labelled fatty acids to the pheromone gland. The incorporation of the labelled acids into pheromone components and precursors was determined by gas chromatography with flame ionization detection and mass spectrometry in the selected ion monitoring mode. The labelling experiments suggest that the pheromone components (E)- and (Z)-12-tetradecenyl acetates are biosynthesized from palmitic acid by δ14 desaturation, followed by chain shortening (β-oxidation), reduction, and acetylation. This is the first confirmation of a Δ14 desaturase in an eukaryotic system.     

Resolution and Synthesis of (S)-1-(2-Naphthyl)ethanol with Immobilized Pea Protein: As a New Biocatalyst

(S)-1-(2-Naphthyl)ethanol was yielded by immobilized pea (Pisum sativum L.) protein (IPP) from (R, S) 2-naphthyl ethanol (>99% ee, yield; about 50%), in which the (R)-enantiomer was selectively oxidized to 2-acetonaphthone. IPP could be reused consecutively at least three times without any decrease of yield and optical purity.     

Cyclopalladation of N-phenylbenzamides: Synthesis and structure of bimetallic palladium(II)-complexes

Three bimetallic palladium(II) complexes were generated by cyclopalladation of N-methyl-N-phenylbenzamide derivatives, substrates known to undergo oxidative intramolecular cross-coupling via palladium catalysis. These isolable Pd-complexes were characterized by X-ray crystallography. Stoichiometric and catalytic experiments with [(3-methoxy-N-methyl-N-phenylbenzamide)Pd(μ-TFA)]₂ were investigated, and this palladium complex was found to be an effective precatalyst for oxidative cross-coupling.     

A Novel Oxy‐Oxonia(Azonia)‐Cope Reaction: Serendipitous Discovery and Its Application to the Synthesis of Macrocyclic Musks

This brief review, including new experimental results, is the summary of a talk at the GDCh conference ‘flavors & fragrances 2013’ in Leipzig, Germany, 11th–13th September, 2013. Musk odorants are indispensable in perfumery to lend sensuality to fine fragrances, a nourishing effect to cosmetics, and a comforting feeling to laundry. We have recently found serendipitously a new oxy‐oxonia‐Cope rearrangement. In this account, we review the background of oxonia‐sigmatropic rearrangements and the discovery of this novel reaction. Special attention is focused on the versatile lactone and lactam formation reactions via [n+4] ring enlargement and the macrocyclization in the synthesis of new macrocyclic musks. The synthesized structures provide new insights into the structure? odor relationships of musks.     

A simple and sensitive spectrofluorimetric method for the determination of furosemide using zinc(II)–1,4‐bis(imidazol‐1‐ylmethyl)benzene complexes

A novel spectrofluorometric method for the determination of furosemide (FUR) is described. The method is based on enhancement of fluorescence emission of FUR in the presence of zinc (II) complexes of 1,4‐bis(imidazol‐1‐ylmethyl)benzene. Under optimum conditions, the enhanced fluorescence intensity is linearly related to the concentration of FUR. The proposed method has been successfully applied to the determination of FUR in pharmaceutical preparations. The possible mechanism of this reaction is discussed briefly based on data from fluorescence spectroscopy, UV–vis absorption and infrared spectroscopy. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and Biochemical Evaluation of the Novel Steroid Androsta-4,6,8(9)-Triene-3,17-Dione

Abstract

According to a proposed aromatisation mechanism by which estrogens are biosynthesized from androgens, the novel steroid androsta-4,6,8(9)-triene-3,17-dione (FCE 24918) should behave as a suicide substrate for aromatase. The synthesis of this triene steroid has been accomplished starting from androsta-4,7-diene-3,17-dione (4) by the acid-catalysed cleavage of the corresponding 7,8α-epoxide, 5, and it was obtained together with androsta-4,6,8(14)-triene-3,17-dione (FCE 24917) as a side product. The time-dependent inactivation of placental aromatase by the two isomers was studied comparatively and showed that the 4,6,8(9)-triene moiety acts as a latent alkylating group.     

Optimization and field evaluation of the sex pheromone of Trichophysetis cretacea (Lepidoptera,Crambidae) for pest monitoring

Field studies using the synthetic sex pheromone of Trichophysetis cretacea, a trinary blend of (Z)‐11‐hexadecenyl acetate (Z11‐16:OAc), (Z)‐11‐hexadecenal (Z11‐16:Ald) and (Z)‐11‐hexadecenol (Z11‐16:OH), were performed in Sichuan to determine operational parameters for detection and control, such as dispenser type, blend ratio, dosage, and trap type, height and density. Of three pheromone dispensers tested, grey halo‐butyl isoprene elastomeric septa were significantly more effective than polyvinyl chloride capillary tubing or silicone rubber septa. The ratio of the three components in the blend significantly affected moth catch. In the halo‐butyl isoprene septa, the most effective ratio was 5 : 2 : 1 Z11‐16:OAc:Z11‐16:Ald:Z11‐16:OH. Sticky wing traps caught significantly more moths than water, noctuid moth or cone funnel traps. The most effective height at which wing traps were hung was 20 cm above the jasmine plants. Optimum trap density was 45 traps per hectare. Addition of volatile jasmine compounds did not increase the attractiveness of the sex pheromone. A dosage of 50 μg Z11‐16:OAc per lure was most effective in the autumn weather conditions of Quanwei. These data provide sufficient information to develop effective protocols for using the T. cretacea pheromone to detect and monitor this pest in the jasmine fields.     

A Facile Synthesis and Anti-Avian Influenza Virus (H5N1) Screening of Some Novel Pyrazolopyrimidine Nucleoside Derivatives

Treatment of 5-amino-1-(9-methyl-5,6-dihydronaphtho[1′,2′:4,5]thieno[2,3-d]pyrimidin-11-yl)-1H-pyrazole-4-carbonitrile (1) with formic acid afforded pyrazolo[3,4-d]pyrimidin-4-one derivative 2. The sodium salt of the latter compound (generated in situ) was treated with some alkyl halides to afford the corresponding N-substituted compounds 3–7. The siloxy derivative 8 (generated also in situ from 2) was ribosylated and glycosylated to yield compounds 9 and 11, respectively. Deprotection of compounds 9 and 11 in methanolic ammonia produced the free nucleosides 10 and 12, respectively. Moreover, the prepared compounds were tested for antiviral activity against H5N1 virus [A/chicken/Egypt/1/2006] and some of them revealed moderate results compared with the other tested compounds.     

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

Although initially considered an esoteric reagent, SmI₂ has become a common tool for synthetic organic chemists. SmI₂ is generated through the addition of molecular iodine to samarium metal in THF.^1,2-3 It is a mild and selective single electron reductant and its versatility is a result of its ability to initiate a wide range of reductions including C-C bond-forming and cascade or sequential reactions. SmI₂ can reduce a variety of functional groups including sulfoxides and sulfones, phosphine oxides, epoxides, alkyl and aryl halides, carbonyls, and conjugated double bonds.^2-12 One of the fascinating features of SmI-₂-mediated reactions is the ability to manipulate the outcome of reactions through the selective use of cosolvents or additives. In most instances, additives are essential in controlling the rate of reduction and the chemo- or stereoselectivity of reactions.^13-14 Additives commonly utilized to fine tune the reactivity of SmI₂ can be classified into three major groups: (1) Lewis bases (HMPA, other electron-donor ligands, chelating ethers, etc.), (2) proton sources (alcohols, water etc.), and (3) inorganic additives (Ni(acac)₂, FeCl₃, etc).³Understanding the mechanism of SmI₂ reactions and the role of the additives enables utilization of the full potential of the reagent in organic synthesis. The Sm-Barbier reaction is chosen to illustrate the synthetic importance and mechanistic role of two common additives: HMPA and Ni(II) in this reaction. The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot.^1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported,^1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products.^16,17 Previous studies on the effect of additives on SmI₂ reactions have shown that HMPA enhances the reduction potential of SmI₂ by coordinating to the samarium metal center, producing a more powerful,^13-14,18 sterically encumbered reductant^19-21 and in some cases playing an integral role in post electron-transfer steps facilitating subsequent bond-forming events.²² In the Sm-Barbier reaction, HMPA has been shown to additionally activate the alkyl halide by forming a complex in a pre-equilibrium step.²³Ni(II) salts are a catalytic additive used frequently in Sm-mediated transformations.^24-27 Though critical for success, the mechanistic role of Ni(II) was not known in these reactions. Recently it has been shown that SmI₂ reduces Ni(II) to Ni(0), and the reaction is then carried out through organometallic Ni(0) chemistry.²⁸These mechanistic studies highlight that although the same Barbier product is obtained, the use of different additives in the SmI₂ reaction drastically alters the mechanistic pathway of the reaction. The protocol for running these SmI₂-initiated reactions is described.     

Efficient preparation of (R)-alpha-monobenzoyl glycerol by lipase catalyzed asymmetric esterification: optimization and operation in packed bed reactor

Optically active (R)-alpha-monobenzoyl glycerol (MBG) was synthesized by Candida antarctica lipase B (CHIRAZYME L-2) catalyzed asymmetric esterification of glycerol with benzoic anhydride in organic solvents. Various conditions, such as the type and composition of the organic solvent, water content of the system, reaction temperature, and concentrations of the substrates were systematically examined and optimized in screw-capped test tubes with respect to both the reaction rate and the enzyme selectivity. 1,4-Dioxane was found to be the best solvent and no additional water was needed for the system. The optimum temperature was around 30 degrees C, while the most suitable substrate concentrations were 100 mM each for glycerol and benzoic anhydride, respectively. However, when excessive anhydride (e.g., 200 mM) was used, the produced MBG could be further transformed into 1,3-dibenzoyl glycerol (DBG) by the same enzyme with a priority to (S)-MBG, resulting in a significant improvement of the product optical purity from ca. 50-70% e.e. Under optimal conditions (100 mM glycerol, 100-200 mM benzoic anhydride, dioxane, 25-30 degrees C), the enzymatic synthesis of (R)-MBG was successfully operated in a packed-bed reactor for about 1 week, with an average productivity of 0.79 g MBG/day/g biocatalyst in the case of continuous operation and 0.94 g MBG/day/g biocatalyst in the case of semicontinuous operation. After refinement and preferential crystallization of the crude product, (R)-MBG could be obtained in an almost optically pure form (>98% e.e.).     

普通大蓟马聚集信息素的分离和鉴定

【目的】普通大蓟马Megalurothrips usitatus是我国华南地区重要的豆科害虫,给我国豇豆种植产业带来巨大损失。开发利用基于聚集信息素的引诱剂是普通大蓟马的绿色防控措施之一,对于普通大蓟马生物防治具有重要意义。【方法】采用Y型嗅觉仪测定普通大蓟马雌雄成虫对其雌虫和雄虫气味源的嗅觉反应;用顶空固相微萃取法(head space solid-phase microextraction, HS-SPME)和溶液浸提法提取普通大蓟马雌雄成虫挥发物;应用气质联用仪(gas chromatography-mass spectrometry, GC-MS)对收集的气体挥发物和正己烷提取物进行活性成分分离鉴定;应用Y型嗅觉仪测定人工合成聚集信息素组分对雌雄成虫的引诱效果。【结果】行为学试验结果表明,普通大蓟马雄成虫气味源对其雌雄成虫均具有显著的引诱作用,而雌成虫气味源则没有。顶空固相微萃取法和溶液浸提法均可提取雄成虫挥发物主要组分,但顶空固相微萃取法获得的TIC图基线平稳,杂峰少,提取效果优于溶剂浸提法。GC-MS分析结果表明,普通大蓟马雄成虫挥发物中主要含有 1种化合物,为反式,反式-金合欢醇乙酸酯［(E,E)-farnesyl acetate］,该化合物在雌成虫挥发物中不存在。室内行为学实验结果表明,特定剂量的人工合成的(E,E)-farnesyl acetate对普通大蓟马雌雄成虫均具有显著的引诱作用。【结论】本研究证明了普通大蓟马雄成虫可以释放聚集信息素,并鉴定了其主要组分(E,E)-farnesyl acetate,为应用聚集信息素开展普通大蓟马的监测和诱杀提供了基础。     

Efficient and Stable TiO2:Pt–Cu(In,Ga)Se2 Composite Photoelectrodes for Visible Light Driven Hydrogen Evolution

Novel thin film composite photocathodes based on device‐grade Cu(In,Ga)Se₂ chalcopyrite thin film absorbers and transparent conductive oxide Pt‐implemented TiO₂ layers on top are presented for an efficient and stable solar‐driven hydrogen evolution. Thin films of phase‐pure anatase TiO₂ are implemented with varying Pt‐concentrations in order to optimize simultaneously i) conductivity of the films, ii) electrocatalytic activity, and iii) light‐guidance toward the chalcopyrite. Thereby, high incident‐photon‐to‐current‐efficiencies of more than 80% can be achieved over the full visible light range. In acidic electrolyte (pH 0.3), the most efficient Pt‐implemented TiO₂–Cu(In,Ga)Se₂ composite electrodes reveal i) photocurrent densities up to 38 mA cm^?2 in the saturation region (?0.4 V RHE, reversible hydrogen electrode), ii) 15 mA cm^?2 at the thermodynamic potential for H₂‐evolution (0 V RHE), and iii) an anodic onset potential shift for the hydrogen evolution (+0.23 V RHE). It is shown that the gradual increase of the Pt‐concentration within the TiO₂ layers passes through an efficiency‐ and stability‐maximum of the device (5 vol% of Pt precursor solution). At this maximum, optimized light‐incoupling into the device‐grade chalcopyrite light‐absorber as well as electron conductance properties within the surface layer are achieved while no degradation are observed over more than 24 h of operation.     

Improved enzymatic two-phase biotransformation for (R)-phenylacetylcarbinol: Effect of dipropylene glycol and modes of pH control

An octanol/aqueous two-phase process for the enzymatic production of (R)-phenylacetylcarbinol (PAC) has been investigated further with regard to optimal pH control and replacement of 2.5?M MOPS buffer by a low cost solute. The specific rate of PAC production in the 2.5?M MOPS system controlled at pH?7 was 0.60?mg?U^?1?h^?1 (reaction completed at 34?h), a 1.6 times improvement over the same 2.5?M MOPS system without pH control (0.39?mg?U^?1?h^?1 at 49?h). An improved stability of PDC was evident at the end of biotransformation for the pH-controlled system with 84% residual carboligase activity, while 23% of enzyme activity remained in the absence of pH control. Lowering the MOPS concentration to 20?mM resulted in a lower benzaldehyde concentration in the aqueous phase with a major increase in the formation of by-product acetoin and three times decreased PAC production (0.21?mg?U^?1?h^?1). Biotransformation with 20?mM MOPS and 2.5?M DPG as inexpensive replacement of high MOPS concentrations provided similar aqueous phase benzaldehyde concentrations compared to 2.5?M MOPS and resulted in a comparable PAC concentration (92.1?g?L^?1 in the total reaction volume in 47?h) with modest formation of acetoin.     

Synthesis and polymerization of benzyl (3R,4R)-3-methylmalolactonate via enzymatic preparation of the chiral precursor

β-methylaspartate ammonia-lyase, EC 4.3.1.2, (β-methylaspartase) from Clostridium tetanomorphum was used to produce a 40/60 molar ratio of (2S,3R) and (2S,3S)-3-methylaspartic acids, 2a and 2b , respectively, from mesaconic acid 1 as substrate, on a large scale. To prepare (3R,4R)-3-methyl-4-(benzyloxycarbonyl)-2-oxetanone (benzyl 3-methylmalolactonate) 6, 2a and 2b were transformed, in the first step, into 2-bromo-3-methylsuccinic acids 3a and 3b and separated. After three further steps, (2S,3S)- 3a yielded the α,β-substituted β-lactone (3R,4R) 6 with a very high diastereoisomeric excess (>95% by chiral gas chromatography). The corresponding crystalline polymer, poly[benzyl β-(2R,3S)-3-methylmalate] 8 , prepared by an anionic ring opening polymerization, was highly isotactic as determined by ¹³C NMR. Catalytic hydrogenolysis of lactone 6 yielded (3R,4R)-3-methyl-4-carboxy-2-oxetanone (3-methylmalolactonic acid) 7 , to which reactive, chiral, or bioactive molecules can be attached through ester bonds leading to polymers with possible therapeutic applications. Because of the ability of β-methylaspartase to catalyse both syn- and anti-elimination of ammonia from (2S,3RS)-3-methylaspartic acid 2ab at different rates, the (2S,3R)-stereoisomer 2a was retained and isolated for further reactions. These results permit the use of the chemoenzymatic route for the preparation of both optically active and racemic polymers of 3-methylmalic acid with well-defined enantiomeric and diastereoisomeric compositions. Chirality 10:727–733, 1998. © 1998 Wiley-Liss, Inc.