(+)-Dehydroabietic Acid,an Abietane-Type Diterpene,Inhibits Staphylococcus aureus Biofilms in Vitro

Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.     

米根霉发酵生产L(+)-乳酸研究进展

米根霉是生产绿色平台生物化学品L(+) 乳酸的理想菌种 ,目前集中在发酵工艺的优化、新型生物反应器的设计以及细胞固定化等方面的研究 ,通过控制米根霉菌体形态使之自聚集成为一定大小的球体进行乳酸发酵 ,操作简便、费用低。建议今后从应用代谢工程技术定向选育米根霉L(+) 乳酸高产菌 ,改进发酵设备、改良提取工艺 ,合理控制乳酸产品的构型等几个方面着手进行进一步研究 ,从而降低乳酸生产原料的成本 ,扩大L(+) 乳酸的应用领域。     

New,unusual long chain fatty acid (argemonic acid) fromArgemone Mexicana

An unusual long chain fatty acid has been isolated from argemone oil. By chemical degradation and by spectral analysis, the acid now is shown to be (+) 6-hydroxy-6-methyl-9-oxo-octacosanoic acid and designated as argemonic acid.     

Synthesis, electro-spectroelectrochemical characterization and electrocatalytic behavior towards dioxygen reduction of a new water-soluble cobalt phthalocyanine containing naphthoxy-4-sulfonic acid sodium salt

A new water-soluble cobalt phthalocyanine, 2(3), 9(10), 16(17), 23(24)-tetrakis(4-(1-naphthoxy-4-sulfonic acid sodium salt)) phthalocyaninato cobalt(II) NhtCoPc, where Nht indicates naphthoxy-4-sulfonic acid sodium salt, was synthesized and its electro-spectroelectrochemical and electrocatalytic behavior towards oxygen reduction reaction were investigated in details. The complexation reaction was monitored with the UV-vis spectral changes of NhtH₂Pc in methanol solution. The reaction was completed when the main Q-band was observed in maximum intensity. The electrochemical studies showed that the cobalt complex exhibited two reversible one-electron reductions with the corresponding anodic wave and an irreversible oxidation reaction in DMSO solution. These reduction processes were assigned to Co(2+)Pc(2−)/Co(+)Pc(2−) and Co(+)Pc(2−)/Co(+)Pc(3−) couples, respectively. The well-defined UV-vis spectra of the mono-anionic species [NhtCo(+)Pc(2−)]⁻, di-anionic species [NhtCo(+)Pc(3−)]²⁻, and mono-cationic species [NhtCo(3+)Pc(2−)]⁺, were obtained by the applied potentials (E_app = −0.60, −1.40, and 0.70 V, respectively) in a thin-layer cell. NhtCoPc was incorporated into the conductive polyaniline (PAni) films as a dopant-anion during electropolimerization in acid medium, and thus formed the Pt/PAni-NhtCoPc electrode. This modified electrode was characterized by scanning electron microscopy (SEM), as well. The addition of NhtCoPc to the polymerization solution changes markedly the morphology of the films obtained and increases the redox-activity towards oxygen reduction of the PAni film formed compared to those of Pt/PAni and bare platinum electrodes in the same experimental conditions.     

Absolute configuration of 12-Oxo-10,15(Z)-phytodienoic acid

12-Oxo-10,15(Z)-phytodienoic acid biosynthesized from 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid using a preparation of corn (Zea mays L) hydroperoxide dehydrase recently was found to be a mixture of enantiomers in a ratio of 82∶18 (Hamberg, M., and Hughes, M.A. (1988)Lipids 23, 469–475). In this work, 12-oxophytodienoic acid and (+)-7-iso-jasmonic acid were converted into a common derivative, methyl 3-hydroxy-2-pentyl-cyclopentane-1-octanoate. From gas liquid chromatographic analysis of the (−)-menthoxycarbonyl derivative of methyl 3-hydroxy-2-pentyl-cyclopentane-1-octanoates prepared from 12-oxophytodienoic acid and (+)-7-iso-jasmonic acid, it could be deduced that the major enantiomer of 12-oxophytodienoic acid had the 9(S),13(S) configuration. Therefore, in the major enantiomer of 12-oxophytodienoic acid, the configurations of the side chainbearing carbons are identical to the configurations of the corresponding carbons of (+)-7-iso-jasmonic acid, thus giving support to previous studies indicating that 12-oxophytodienoic acid serves as the precursor of (+)-7-iso-jasmonic acid in plant tissue. When absolute configurations of C-9 and C-13 are not specifically indicated, phytonoic acid is used to denote 2-pentyl-cyclopentane-1-octanoic acid in which the two side chains have thecis relationship, whereas phytonoic acid (trans isomer) denotes 2-pentyl-cyclopentane-1-octanoic acid in which the two side chains have thetrans relationship.     

炔草酯的合成工艺研究

研究了以R-(+)-2-(4-羟基苯氧基)丙酸、氯丙炔、2,3-二氟-5-氯吡啶为原料,经由R-(+)-2-(4-羟基苯氧基)丙酸炔丙酯制备炔草酯的合成工艺,并讨论了溶剂、反应时间、反应温度对合成目标产物的影响。结果表明,以DMF为溶剂,碳酸钾为缚酸剂,在80℃左右条件下,R-(+)-2-(4-羟基苯氧基)丙酸与氯丙炔反应6 h,再升温到95℃左右,滴加2,3-二氟-5-氯吡啶反应10 h,过滤、重结晶得到炔草酯,收率达到89%,光学纯度为99%。     

2,2-二甲基环丙烷甲酸的合成与拆分

S-( )-2,2-二甲基环丙烷甲酸是合成西司他丁(一种肾脱氢二肽酶抑制剂)的关键中间体,今设计了一条新的2,2-二甲基环丙烷甲酸合成路线并改进了拆分工艺,它是以异戊烯酸为原料,经酸的酯化、烯键的环丙烷化、酯水解制得2,2-二甲基环丙烷甲酸,收率为44．1％。其中,环丙烷化反应用锌粉／氯化亚铜-乙酰氯作为催化剂,二溴甲烷作为环丙烷化试剂,这样可以在温和的条件下进行反应,降低成本。此外用L-肉碱草酸盐作为手性拆分试剂,经酰化、成盐、部分结晶、水解得到S-( )-2,2-二甲基环丙烷甲酸．收率为16．7％,手性纯度大于95％．此路线工艺简单、环境友好、成本较低,易于工业化。     

Comparative effects of (−)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo

(−)-Hydroxycitrate and (+)-allo-hydroxycitrate were investigated for their effects on lipid synthesis in vivo under conditions of either high carbohydrate feeding or 24 hr fasting. Changes in rates of lipid synthesis resulting from the oral administration of these compounds were monitored with the use of radiolabeled H₂O, alanine, and acetate. In the fed rat, (−)-hydroxycitrate significantly reduced the incorporation of H₂O and alanine into fatty acids and cholesterol. An increased incorporation of labeled H₂O into fatty acids but no change in cholesterol synthesis in the fasted rat suggested that (−)-hydroxycitrate may be an activator of acetyl CoA carboxylase. With (−)-hydroxycitrate administration, acetate incorporation into fatty acids and cholesterol was subject to pool dilution effects under fed or fasted states. (+)-allo-Hydroxycitrate was ineffective in modulating the rates of fatty acid synthesis under either nutritional condition. Both (−)-hydroxycitrate and (+)-allo-hydroxycitrate were shown to be in vitro activators of acetyl CoA carboxylase, the former being a much stronger activator than the latter. Thus, stereospecificity of the hydroxycitrate isomers was demonstrated in both the inhibition of lipid synthesis (previously shown to occur at adenosine triphosphate citrate lyase) and the stimulation of fatty acid synthesis (possibly occurring at acetyl CoA carboxylase).     

The stereochemistry of enzymic hydration and of chemical cleavage of D-(+)-cis-12,13-epoxyoleic acid (Vernolic acid)

The absolute optical configurations of (+)-threo-12,13-dihydroxyoleic acid, derived by enzymic hydration of endogenous vernolic acid in crushedVernonia anthelmintica seed, and of (−)-threo-12,13-dihydroxyoleic acid, derived by acetolysis-hydrolysis of vernolic acid, have been determined. The absolute configuration of the (+)-enantiomer is L-12,D-13-dihydroxyoleic acid and, as the parent vernolic acid is known to be D-12,D-13-epoxyoleic acid, the stereochemistry of the enzymic hydration is thus shown to involve attack by hydroxyl at the 12 position with inversion at that position. Chemical cleavage of vernolic acid, on the other hand, involves preferential nucleophilic attack, with inversion, at the 13 position.     

Sesamin is a potent and specific inhibitor of Δ5 desaturase in polyunsaturated fatty acid biosynthesis

Incubation with sesame oil increases the mycelial dihomo-γ-linolenic acid content of an arachidonic acid-producing fungus,Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989)J. Am. Oil Chem. Soc. 66, 237–241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits Δ5 desaturase at low concentrations, but does not inhibit Δ6, Δ9 and Δ12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (K_i for rat liver Δ5 desaturase, 155 μM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin, also inhibited only Δ5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of Δ5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals. On leave from Suntory Ltd.     

R(+)对羟基苯氧基丙酸炔丙酯的合成

报道了合成超高效除草剂炔草酯的中间体R(+)对羟基苯氧基丙酸炔丙酯的方法。以(S)-(-)乳酸甲酯为原料,先与对甲苯磺酰氯反应制备S-对甲苯磺酰乳酸甲酯,再与对苯二酚和丙炔醇反应,制备R(+)对羟基苯氧基丙酸炔丙酯,总收率76%。旋光度为[α]2D5=+37.5。     

Constitution of scheffleroside: a spermicidal saponin from Schefflera capitata

While screening Indian plants for biological activities, it was observed that a 2% aqueous solution of the crude 70% aqueous ethanolic extract of Schefflera capitata showed significant activity against both rat and human spermatozoa. The new saponin, melting point 230-232 degrees, gives on acid hydrolysis D(+)-fucose (1 mole), D(+)-galactose (1 mole), D(+)-glucoronic acid (1 mole) and echinocystic acid (1 mole). Its structure has been tentatively assigned to scheffleroside.     

离子交换树脂催化合成L-（＋）-酒石酸二乙酯的研究

以L-（＋）-酒石酸和乙醇为原料,直接合成了L-（＋）-酒石酸二乙酯,其结构经过IR确证,比旋光度经旋光仪测定。通过正交实验得优化反应条件为：L-（＋）-酒石酸0.6mol,n（酒石酸）∶n（乙醇）为1：5,带水剂CCl4用量70mL,催化剂用量为20g,酯化反应温度69℃,回流反应约5h,酯收率93%。催化剂使用寿命较长,再生能力较强。     

Synthesis and characterization of (S)-3-benzoylthio-2-methylpropionic acid

以硫代乙酸、甲基丙烯酸为原料,经过缩合、水解-酯化得到3-苯甲酰巯基-2-甲基丙酸的消旋体,经化学拆分得到(S)-3-苯甲酰巯基-2-甲基丙酸。综合考察了缩合、水解-酯化、拆分过程中影响反应的因素,结果表明：硫代乙酸与甲基丙烯酸摩尔比为1.4︰1,反应时间为2 h、反应温度为93 ℃条件下,可以得到收率为95.6%的3-乙酰巯基-2-甲基丙酸（缩合物A）;控制釜温不超过20 ℃,将缩合物A加入11.8%的氢氧化钠水溶液中进行水解,水解完成后将下层钠盐投回釜内,然后在低温下滴加苯甲酰氯,反应进行2 h后将釜液调至酸性,产品逐渐析出,计算得水解-酯化总收率为96.7%;利用拆分剂D-(+)-N-苄基-α-苯乙胺对产品拆分,拆分收率为36.0%,综合以上三步总收率可达33.3%。其结构经核磁、质谱、红外分析确认且由X射线衍射分析结晶度非常高。     

The absolute optical configurations of the isomeric 9,10-epoxystearic, 9,10-dihydroxystearic and 9,10,12-trihydroxystearic acids

The absolute optical configuration of (−)-cis-9,10-epoxystearic acid has been verified as being L. Here (−)-erythro-9,10-dihydroxystearic acid, isolated from castor oil, was converted by stereospecific reactions to (+)-cis-9,10-epoxystearic acid and was thereby proved to be D-9,D-10-dihydroxystearic acid. Removal of the D-12-hydroxy group from the higher meltingerythro-9,10,12-trihydroxystearate derived from ricinoleic acid, after protection of the glycol group, gave the L-9,L-10-dihydroxystearate derivative. This proved the high melting diastereoisomer to be L-9,L-10,D-12-trihydroxystearate and directly verified the supposition that the higher melting, arsenite-complexing diastereoisomer of such oxidation pairs has thetrans-10,12-diol grouping. On this basis, the higher meltingthreo-trihydroxystearate from ricinoleate must be D-9,L-10,D-12-trihydroxystearate and removal of the 12-hydroxy group must give D-9,L-10-dihydroxystearate which proved to be the levorotatory enantiomer. The dextrorotatory L-9,D-10-dihydroxystearate was transformed by stereospecific reactions to (+)-trans-9,10-epoxystearic acid, thereby defining the absolute configurations oftrans-9,10-epoxystearic acids. On the basis of these results conclusions may be drawn as to the stereospecificity and site of action of enzymes which hydrate 9,10-epoxystearic acids.     

手性双苯并咪唑化合物合成方法的改进

通过改进的Phillips方法用L（＋）－酒石酸、L（＋）－谷氨酸及L( )-天冬氨酸与邻苯二胺以盐酸盐形式在乙二醇中反应,合成了3种手性双苯并咪唑化合物（1R,2R）－二（2－苯并咪唑）乙二醇（HlbbImed);(1S),3-二（2－苯并咪唑）－1－丙胺（bbImpa),(1s),2-二（2－苯并咪唑）乙胺（bbImea);反应产率比文献方法提高。还用KBH4分别测定了各手性化合物对苯乙酮和丁酮的不对称氢化反应性能。     

Chemoenzymatic production of (+)-coriolic acid from trilinolein: Coupled synthesis and extraction

Chemoenzymatic conversion of trilinolein to (+)-coriolic acid was investigated in this work. Lipase-catalyzed hydrolysis of trilinolein and lipoxygenation of liberated linoleic acid were coupled in a two-phase medium that consisted of a pH 9 borate buffer and a water-immiscible organic solvent (octane). High concentrations of trilinolein could be dissolved in the organic phase (up to 340 mM). Linoleic acid, liberated after hydrolysis, transferred to the aqueous phase and was enzymatically converted to the preferred 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid with soybean lipoxygenase-1. This product, which remained in the aqueous phase, could be recovered by centrifugation and then chemically reduced to (+)-coriolic acid (purity >95%). Recovery of this compound by liquid-liquid extraction was easy. The structure of (+)-coriolic acid has been confirmed by ¹H nuclear magnetic resonance spectroscopy, mass spectrometry, and infrared spectroscopy. High yields were obtained with pure trilinolein or sunflower oil as initial substrates.     

D-(+)-对二苯甲酰酒石酸插层水滑石的组装与表征

以Mg0.67Al0.33(OH)2(CO3)0.165.0.58H2O为前体(主体),乙醇为分散剂,在pH=6,温度140℃条件下用离子交换法组装了大分子D-(+)-对二苯甲酰酒石酸(DBTA,客体)插层水滑石。并用XRD,FTIR,DSC-TG,ICP,EA等手段对样品进行了表征。结果表明,通过控制离子交换条件,可成功将手性大分子DBTA插入水滑石,得到的材料结构完整,晶相单一,具有良好的层状结构,其层间距由0.76 nm扩大为1.98 nm。DBTA插入后,分解温度由297℃上升到387℃,复合水滑石材料的热稳定性大幅提高。     

乙胺丁醇的合成

对手性抗结核药物盐酸乙胺丁醇的关键中间体———乙胺丁醇的合成进行了系统研究。以1 丁烯、氯气和乙腈为原料,合成了(R,S) 2 氨基丁醇,收率50 7%;选用L (+) 酒石酸拆分(R,S) 2 氨基丁醇,得到酸式(S) 2 氨基丁醇的L (+) 酒石酸盐,收率94 3%;滤液经处理后,得到酸式(R) 2 氨基丁醇的L (+) 酒石酸盐,收率99 0%;将两种酸式2 氨基丁醇的L (+) 酒石酸盐分别进行水解,得到(S) 2 氨基丁醇和(R) 2 氨基丁醇,收率均达85 0%以上;最后,以(S) 2 氨基丁醇和1,2 二氯乙烷为原料,合成了乙胺丁醇,收率81 3%。此外,选用骨架镍催化剂,对(R) 2 氨基丁醇进行了消旋化反应,收率72 7%;将水解得到的酒石酸钠晶体用于L (+) 酒石酸的回收,收率82 5%。     

A Case of Convergent Evolution: The Bacterial Sesquiterpene Synthase for 1-epi-Cubenol from Nonomuraea coxensis

A terpene synthase from Nonomuraea coxensis was identified as (+)-1-epi-cubenol synthase. The enzyme is phylogenetically unrelated to the known enzyme of the same function that is widespread in streptomycetes. Isotopic labelling experiments were performed to unambiguously assign the NMR data and to investigate hydrogen migrations during terpene cyclisations. Epoxidations of (+)-1-epi-cubenol and of the plant derived compounds (−)-cubenol and (−)-1-epi-cubenol confirmed the structure of a natural product isolated from the brown alga Dictyopteris divaricata and allowed to conclude on its absolute configuration. The crystal structures of the epoxides from (+)- and (−)-1-epi-cubenol and the acid catalysed conversion into an isomeric ketone are reported.