手性苯基环氧乙烷的生物不对称合成

以苯乙烯为唯一碳源和能源,从不同来源的土壤样品中初筛分离出12株好氧细菌和2株真菌,经复筛,对液体培养物进行手性气相色谱分析,得到一株产生手性苯基环氧乙烷活力较高的菌种PS-1206,并对其发酵、产酶及苯乙烯的全细胞转化进行了研究,利用微生物细胞在30℃,pH 7.0,10mmol/L磷酸缓冲液中转化0.5%苯乙烯10h,获得?苯基环氧乙烷,e.e%值为80%,转化产率为35%。     

丙氨酸的双不对称合成

<正> 氨基酸的不对称合成是近年来十分热门的研究课题之一。八十年代发展起来的双不对称合成新策略为高光学纯度物质的合成提供了一条有益的思路。本文考察了在手性相转移催化剂催化下,通过邻苯二甲酰胺钾与手性α-溴代丙酸龙脑醋之间的Gabriel反应制取光学活性丙氨酸的双不对称合成反应,观察到了显著的双不对称诱导效应。     

乙醇系统HPLC分析PTC－氨基酸的条件优化

首次报道用乙醇系统分析ＰＴＣ－氨基酸的新方法中各衍生物获得最佳分离的建立过程。ＰＴＣ－氨基酸衍生后溶于Ａ溶液,然后进样于４μｍＮｏｖａＰａｋＣ１８柱（３．９ｍｍ×１５０ｍｍ）。系统的优化步序包括全面调控流动相的ｐＨ值与ＴＥＡ浓度、乙醇梯度程序、柱温等诸多影响ＨＰＬＣ色谱行为的因素。最适条件为：Ａ溶液含０．１４ＭＧ酸钠、０．７５ｍｌ／ＬＴＥＡ、ＰＨ６．３５;Ｂ溶液为１００％乙醇;柱温３０℃。通过优化的乙醇梯度最终在约４４ｍｉｎ内将１５种ＰＴＣ－氨基酸很好地分离。此法可用于替代代表新科技水平的ＰＴＣ－氨基酸乙腈分析系统。     

空间诱变条件下蜜蜂后代的波动性不对称

利用航天搭载的雄蜂精液对处女王进行人工授精,产卵后大量培育后代蜂王;以SP1、SP2及SP3代蜂王后代工蜂为研究对象,考查波动性不对称(fluctuating asymmetry,FA)在不同代次种群中各对称性状间的表现情况。结果表明:SP1、SP2和SP3代工蜂的前翅长及肘脉a均表现出FA,SP1、SP2代的对照组中均未出现,而SP3代的对照组蜂群则全部表现出FA;与对照蜂群相比,空间诱变后代的前翅长及翅脉a的FA值均较高。此外,讨论FA在蜜蜂种群对生态环境适应性上应用以及利用蜜蜂的FA来监测环境污染的可能性及发展前景。     

面包酵母催化羰基不对称还原合成手性醇的研究

以2-辛酮和4-氯乙酰乙酸乙酯(COBE)为模型底物分别考察了酵母细胞对直链甲基酮和陆羰基酯中的羰基不对称还原情况。实验发现不对称还原2-辛酮的产物主要是S型的2-辛醇,且对映体选择性很高。不对称还原COBE生成的主要是S(D)-型产物,反应COBE的转化率、光学选择性都比较高。同时发现COBE的浓度和产物对不对称还原都有一定负面的影响。     

不对称还原前手性芳香酮微生物的筛选及反应特性

含芳香基手性醇是许多手性药物合成的关键手性砌块,生物催化不对称还原前手性酮是合成该类醇的重要方法之一.以4'-氯-苯乙酮为模型底物,从土壤中筛选得到一株能高效催化前手性芳香酮不对称还原合成相应手性醇的菌株,鉴定表明该菌株为白地霉( Geotrichum candid ).进一步考察了其催化4'-氯-苯乙酮不对称还原的反应特性,发现还原4'-氯-苯乙酮的产物主要为 S-4'-氯苯乙醇.在合适的反应条件下,其产率达到35%,对映选择性高于97%.     

羰基还原酶及其催化不对称合成大基团手性羟基类化合物的研究进展

手性羟基化合物以其独特的光、热和化学性质广泛应用于医药、农药、精细化工、功能材料等行业.立体专一性羰基还原酶能够直接针对关键手性位点催化不对称还原潜手性底物获得目的手性产物.基于羰基还原酶的底物多样性,具有不同化学结构和功能的醇类、酯类、氨基酸、环氧化合物等重要手性中间体能够通过不对称还原途径实现单一光学活性对映体的高效制备.然而,针对具有应用价值的含有大基团、结构复杂的潜手性羰基化合物,已知的羰基还原酶通常催化活性较低.本文综述了生物催化不对称氧化还原反应的特点和规律及其关键立体选择性羰基还原酶的性质和结构特征,并在此基础上,重点针对大基团手性羟基化合物的不对称合成,总结了羰基还原酶及其催化系统开发和应用的研究进展,并进一步提出解决该关键问题的主要发展策略.     

ω-转氨酶不对称合成手性胺及非天然氨基酸的研究进展

ω-转氨酶不对称合成手性胺及非天然氨基酸是目前生物加工过程的研究热点之一。ω-转氨酶具有优良的立体选择性及区域选择性,利用其进行生物催化生产手性胺,已被应用于医药、农药和化工等领域。本文中,笔者综述了ω-转氨酶的基本结构特性,并以转氨酶法制备西他列汀关键中间体等为例,同时阐述了该酶的高通量筛选方法及分子改造方面的研究进展,并对级联反应提高手性胺产量的策略作了进一步讨论。最后,本文简要总结了ω-转氨酶在不对称合成非天然氨基酸中的具体应用。     

Asymmetric induction under confinement

Confinement may efficiently condition the stereochemical outcome of a reaction through space constriction and molecular close contact. This article briefly reviews recent approaches of supramolecular chemistry to achieve chiral confinement. Crystallization is not always possible and the use of chiral crystals or clathrates lacks generality. The construction of solid supramolecular assemblies circumvents some of the problems of the crystal chemistry. In this regard, molecular imprinting of polymeric matrices with orifices mimicking the transition state of an enantioselective process is a very young, promising technique. Zeolites provide porous, rigid environments to host molecules without the need of lucky crystallizations, yet zeolites are not chiral per se and must be chirally modified. Besides, the limited dimension of their pores restricts the size of the guest molecules. Despite these problems, useful asymmetric photochemical reactions have been performed on zeolites. Finally, the formation of pillared lamellar structures, from inorganic salts of tetravalent transition metals covalently grafted with organic chains, is considered. The adequate selection of functionality and chirality of the organic pillars would afford custom-made, highly porous, 3D hybrid organo-inorganic scaffolds. However, the production of asymmetric processes within these layered materials still remains to be seen.     

Asymmetric Reduction of Iminium Salt with Chiral Dihydropyridines

A gram positive bacterium (strain No. 109) isolated from soil as a producer of cyclodextrinase was identified as Bacillus coagulans. The cyclodextrinase from B. coagulans was purified to a homogeneous state by disc-electrophoresis after Streptomycin treatment, DEAE-Sephadex column chromatography, Ultrogel AcA44 gel filtration and hydroxyapatite column chromatography. The molecular weight of the enzyme was determined to be 6.2}10⁴ by sodium dodecyl-sulfate gel electrophoresis. The isoelectric point of the enzyme was pH 5.0. The enzyme was most active at pH 6.2 and 50°C, and stable up to 45°C at pH 7.0 and in the range of pH 6.0 ~ 7.3 at 40°C on 2 hr incubation. This enzyme hydrolyzed linear maltooligosaccharides (such as maltotetraose (G4), maltopentaose (G5) and maltohexaose (G6)) and α-, β- and α-cyclodextrins (CDs) faster than maltotriose (G3) and short chain amylose ( 18), but did not hydrolyze maltose. The rates of hydrolysis for polysaccharides (such as starch, amylose and amylopectin) were below 1 % as compared to that for β-CD. The Km values for G3, G4, G5, G6, short chain amylose ( 18) and α, β- and γ-CD were 4.5, 4.0,2.3,1.5,1.5,10,2.8 and 0.47 mM, respectively. The products with this enzyme had the α-configulation.     

Chiral interaction in peptide molecules: effects of chiral peptide species on helix-sense induction in an N-terminal-free achiral peptide

Noncovalent chiral domino effect (NCDE) has been proposed as terminal-specific interaction upon a 3(10)-helical peptide chain, of which the helix sense is manipulated by an external chiral stimulus (mainly amino acid derivatives) operating on the N-terminus (Inai, Y., et al. J Am Chem Soc 2000, 122, 11731-11732; ibid., 2002, 124, 2466-2473; ibid., 2003, 125, 8151-8162). We have investigated here a helix-sense induction in an optically inactive N-terminal-free nonapeptide (1) through the screening of several peptide species that differ in chiral sequence, chain length, and C-terminal group. Helix-sense induction in peptide 1 depends largely on both the C-terminal chirality and carboxyl group in the external peptide, in which N-carbonyl-blocked amino acids, "monopeptide acids," should be the minimum requirement for effective induction. N-Protected mono- to tetrapeptides of L-Leu residue commonly induce a right-handed helix. NMR study and theoretical computation reveal that the N-terminal segment of peptide 1 binds the N-protected dipeptide molecule through multipoint coordination to induce a right-handed helix preferentially. The present findings not only will improve our understanding of the chiral roles in peptide or protein helical termini, but also might demonstrate potential applications to chirality-responsive materials based on peptide helical fragments.     

Asymmetric synthesis of chiral amines with omega-transaminase.

The asymmetric synthesis of chiral amines using prochiral ketones was carried out with (S)-specific omega-transaminase (omega-TA) from Vibrio fluvialis JS17. This reaction is inhibited severely by both products, (S)-amine and deaminated ketone. In addition, thermodynamic equilibrium strongly favored the reverse reaction. L-Alanine proved to be the best amino donor based on easy removal of the products. Optimal pH of the reactions with both whole cells and cell-free extract was 7. Amino acceptor reactivities of ketone substrates and reaction profiles of the asymmetric synthesis showed that the initial rate as well as the reaction yield were lower when the resulting (S)-amine from a prochiral ketone substrate was a more reactive amino donor. The yield could be increased dramatically by removing pyruvate, which is a more inhibitory product than (S)-alpha-methylbenzylamine [(S)-alpha-MBA] when acetophenone and L-alanine are used as an amino acceptor and donor, respectively. The removal of pyruvate was carried out by incorporating lactate dehydrogenase (LDH) in cell-free extract or by using whole cells. The whole cell reaction yielded a much better result. When 25 mM benzylacetone and 30 mM acetophenone were used as an amino acceptor with 300 mM L-alanine, 90.2% and 92.1% of the reaction yields after 1 day were obtained with whole cells, respectively. Enantiomeric excesses of both (S)-alpha-MBA and (S)-1-methyl-3-phenylpropylamine [(S)-MPPA] were all above 99%.     

生物催化不对称还原制备氟代手性醇

由于氟原子的特殊性质，化合物中引入氟原子可显著改变其物理化学性质。因此，氟原子在药物中的应用越来越广。此外，80%药物分子结构属于手性分子。其中，氟代手性醇常见于手性药物结构中，该类结构的合成方法研究具有重要的意义。不对称还原含氟酮是合成此结构的常见方法。与化学还原方法相比，生物催化还原具有对映选择性强、产率高和易于分离纯化等优点。生物催化，特别是酶催化还原含氟酮类化合物成为手性药物合成领域的研究热点。本文从纯化酶催化和全细胞催化两个方面，综述了近年来含氟酮生物催化还原合成氟代手性醇的研究进展，并分析总结了氟代对酮生物催化还原的影响，最后对生物催化还原法未来的发展进行了展望。     

Asymmetric Autocatalysis Induced by Chiral Crystals of Achiral Tetraphenylethylenes

The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P2₁) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chirality in the crystalline state, which can also act as a chiral substrate and induce enantioselectivity of diisopropylzinc addition to pyrimidine-5-carbaldehyde in asymmetric autocatalysis to give enantiomerically enriched 5-pyrimidyl alkanols with the absolute configuration correlated with that of the chiral crystals. Highly enantioselective synthesis has been achieved using chiral crystals composed of achiral hydrocarbons, tetraphenylethylenes, as chiral inducers. This chemical system enables significant amplification of the amount of chirality using spontaneously formed chiral crystals of achiral organic compounds as the seed for the chirality of asymmetric autocatalysis.     

Asymmetric autocatalysis and its application to chiral discrimination

Chiral pyrimidyl, quinolyl, and pyridyl alkanols act as asymmetric autocatalysts with significant amplification of enantiomeric excess (ee) in the enantioselective addition of diisopropylzinc to pyrimidine-5-, quinoline-3-, and pyridine-3-carbaldehydes, respectively. 2-Alkynyl-5-pyrimidyl alkanol with as low as 0.6% ee automultiplies during the consecutive asymmetric autocatalysis with increasing ee to as high as >99.5%. Asymmetric autocatalysis is applied to chiral discrimination of organic compounds. In the presence of methyl mandelate or 2-butanol with very low ee's (0.05-0.1%) as chiral initiators, the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc affords pyrimidyl alkanol with higher ee's with the correlated absolute configurations to those of the chiral initiators. Chirality of amino acids (such as leucine) and helicenes with very low ee's are also discriminated by asymmetric autocatalysis, affording pyrimidyl alkanol with very high ee's. Asymmetric autocatalysis also discriminates the chirality of primary alcohols-alpha-d, monosubstituted [2.2]paracyclophanes and octahedral cobalt complex with achiral ligands of which the chirality is due to the topology of coordination of the achiral ligand. Even the chirality of inorganic crystals such as quartz and sodium chlorate is discriminated by asymmetric autocatalysis of pyrimidyl alkanol. Thus, asymmetric autocatalysis provides a unique method for the discrimination of chiral compounds and crystals.     

Asymmetric induction in the [4+2]cycloaddition of cyclopentadiene and furan to chiral derivatives of fumaric acid.

[4+2]Cycloaddition reactions of cyclopentadiene (1a) and furan (1b) to N,N'-fumaroyldi[(2R)-bornane-10,2-sultam] (2) and to N,N'-fumaroyldi[(2R)-bornane-10,2-(2'-phenyl-pyrazol-3'-one)] (3) are presented. A correlation between the solvent polarity and the logarithm of the diastereoisomer ratio (dr) was found for the uncatalyzed [4+2]cycloaddition of 1a to 3.     

Asymmetric induction in the 1,3-dipolar cycloaddition of chiral nitrile oxide derived from (2R)-bornane-10,2-sultam.

The efficient preparation of the chiral nitrile oxide derived from N-glyoxyloyl-(2R)-bornane-10,2-sultam is presented. The nitrile oxide was trapped in situ with substituted olefins as dipolarophiles to furnish optically active 2-isoxazolines.