不对称邻二醇的合成及其在有机合成中的应用

综述了对称邻二醇的合成和选择性转换，以及它在立体控制催化剂和天然产物不对称合成等方面的应用。     

过渡金属多相催化剂催化的分子氧选择性氧化邻二醇研究进展

邻二醇选择性氧化断键生成醛、酮和羧酸是重要和基本的有机反应,氧化剂通常采用化学计量的高碘酸盐或四乙酸铅,无论从经济还是环保的角度考虑,这些传统方法都有违绿色化工的发展理念。理论上以分子氧为氧化剂选择性氧化邻二醇断键的副产物只有水,而且分子氧廉价易得,因而具有环境友好和经济可行的双重优势。经过多年探索,人们已发展了多个基于不同过渡金属为活性组分的多相催化剂或催化体系用于分子氧选择性氧化邻二醇断键反应,如钌、金、锰、钴,为未来广泛应用奠定了基础。本文将按贵金属和非贵金属分类综述此类催化剂及相关反应工艺的研究进展,并指出该领域的发展方向     

环氧化物水解酶PvEH3的表达及手性邻二醇的合成

基于环氧化物水解酶（EHs）一级结构的计算机辅助分析,以菜豆（Phaseolus vulgaris）总RNA为模板,采用逆转录PCR和巢式PCR技术扩增了一种新型环氧化物水解酶（PvEH3）的编码基因pveh3。借助表达载体pET-28a（+）将pveh3导入大肠杆菌BL21（DE3）中进行了异源表达。一级和三级结构表明,PvEH3属于α/β水解酶超家族,其催化三联体为环氧化物水解酶Asp¹⁰¹-His²⁹⁷-Asp²⁶²的表达及手性邻二醇的合成,两个保守质子供体为Tyr¹⁵⁰和Tyr²³²。在20℃、pH7.0的反应条件下,PvEH3能催化环氧苯乙烷及其4种衍生物的对映会聚水解。实验结果表明,PvEH3对环氧苯乙烷及其对位取代环氧底物（93.2%、86.6%和85.1% ee_p）的对映会聚性优于其间位取代环氧底物（37.1%和53.3% ee_p）;PvEH3针对5种环氧底物中的环氧苯乙烷具有最高的区域选择性,区域选择性系数α_S和β_R分别为93.9%和99.0%。PvEH3的发现增加了区域选择性高且互补的EHs数目,为单酶催化环氧化物的对映会聚水解提供了更多的选择余地。     

Screening,Molecular Cloning,and Biochemical Characterization of an Alcohol Dehydrogenase from Pichia pastoris Useful for the Kinetic Resolution of a Racemic β‐Hydroxy‐β‐trifluoromethyl Ketone

The stereoselective synthesis of chiral 1,3‐diols with the aid of biocatalysts is an attractive tool in organic chemistry. Besides the reduction of diketones, an alternative approach consists of the stereoselective reduction of β‐hydroxy ketones (aldols). Thus, we screened for an alcohol dehydrogenase (ADH) that would selectively reduce a β‐hydroxy‐β‐trifluoromethyl ketone. One potential starting material for this process is readily available by aldol addition of acetone to 2,2,2‐trifluoroacetophenone. Over 200 strains were screened, and only a few yeast strains showed stereoselective reduction activities. The enzyme responsible for the reduction of the β‐hydroxy‐β‐trifluoromethyl ketone was identified after purification and subsequent MALDI‐TOF mass spectrometric analysis. As a result, a new NADP⁺‐dependent ADH from Pichia pastoris (PPADH) was identified and confirmed to be capable of stereospecific and diastereoselective reduction of the β‐hydroxy‐β‐trifluoromethyl ketone to its corresponding 1,3‐diol. The gene encoding PPADH was cloned and heterologously expressed in Escherichia coli BL21(DE3). To determine the influence of an N‐ or C‐terminal His‐tag fusion, three different recombinant plasmids were constructed. Interestingly, the variant with the N‐terminal His‐tag showed the highest activity; consequently, this variant was purified and characterized. Kinetic parameters and the dependency of activity on pH and temperature were determined. PPADH shows a substrate preference for the reduction of linear and branched aliphatic aldehydes. Surprisingly, the enzyme shows no comparable activity towards ketones other than the β‐hydroxy‐β‐trifluoromethyl ketone.     

Zirconium phosphonate immobilized chiral amino alcohol for heterogeneous enantioselective addition of diethylzinc to benzaldehyde

The chiral (1R,2S)-(−)-2-amino-1,2-diphenylethanol and (1S,2R)-(+)-2-amino-1,2-diphenylethanol had been immobilized on the layered frame of zirconium phosphate to obtain zirconium phosphonates (1R,2S)-(−)-4a and (1S,2R)-(+)-4b. The enantioselective addition of Et₂Zn to benzaldehyde using zirconium phosphonates (1R,2S)-(−)-4a and (1S,2R)-(+)-4b as heterogeneous catalysts yielded secondary alcohol in 80.1% yield and e.e. values of up to 54.3%, which was only 7.6% e.e. lower than that using the corresponding ligands (1R,2S)-(−)-2a and (1S,2R)-(+)-2b as homogeneous catalysts. The zirconium phosphonates (1R,2S)-(−)-4a and (1S,2R)-(+)-4b were characterized by IR, SEM, XRD and TG analysis. SEM and XRD data showed that the catalysts (1S,2R)-(+)-4b and (1R,2S)-(−)-4a were in aggregate and mesopore structure with the same interlayer spacing 2.48 nm and pore diameter 5.6 nm.     

Chitosan chiral ligand exchange membranes for sorption resolution of amino acids

The concept of chiral ligand exchange is employed in the present study to achieve the chiral resolution of tryptophan (Trp) enantiomers by using chitosan (CS) membrane in a sorption resolution mode and copper(II) ion as the complexing ion. CS porous membranes are prepared by freeze-drying method (CS-LT) and sol-gel process at high temperature (CS-HT), respectively, to investigate their sorption resolution characteristics. The proposed CS chiral ligand exchange membranes exhibit good chiral resolution capability. Meanwhile the sorption selectivity of the CS membranes is found to be reversed from L-selectivity at low copper(II) ion concentration to D-selectivity at high copper(II) ion concentration, which is attributable to the stability difference between the copper(II)-L-Trp and copper(II)-D-Trp complexes. Moreover, the CS-HT membrane shows better performance with respect to both sorption selectivity and sorption capability than the CS-LT membrane, which mainly results from its more amorphous structures compared with the more crystalline structures of the CS-LT membrane. The superiority of sorption capability of the CS-HT membrane is also attributable to its larger specific surface area than that of the CS-LT membrane. The results obtained in this study are conducive to the design and fabrication of chiral ligand exchange membranes for enantiomer separation in sorption mode.     

Fluorescence sensors based on chiral polymer for highly enantioselective recognition of phenylglycinol

Chiral polymer P-1 incorporating (R,R)-salen-type unit was synthesized by the polymerization of (R,R)-1,2-diaminocyclohexane with 2,5-dibutoxy-1,4-di(5-tert-butylsalicyclaldehyde)-phenylene (M-1) via nucleophilic addition-elimination reaction, and chiral polymer P-2 incorporating (R,R)-salan-type unit could be obtained by the reduction reaction of P-1 with NaBH₄. The fluorescence response of two chiral polymers P-1 and P-2 on (R)- or (S)-phenylglycinol were investigated by fluorescence spectra. The fluorescence intensities of two chiral polymers P-1 and P-2 show gradual enhancement upon addition of (R)- or (S)-phenylglycinol and keeps nearly linear correlation with the concentration molar ratios of (R)- or (S)-phenylglycinol. But both P-1 and P-2 exhibited more sensitive response signals for (S)-phenylglycinol. The values of enantiomeric fluorescence difference ratio (ef) are 1.84 and 2.05 for P-1 and P-2, respectively. The results also showed that two chiral polymers P-1 and P-2 can also be used as fluorescence sensors for enantiomer composition determination of phenylglycinol.     

A fluorescence sensor based on chiral polymer for highly enantioselective recognition of phenylalaninol

The chiral polymer P-1 incorporating (S)-2,2′-binaphthol (BINOL) and (S)-2,2′-binaphthyldiamine (BINAM) moieties in the main chain of the polymer backbone was synthesized by the polymerization of (S)-6,6′-dibutyl-3,3′-diformyl-2,2′-binaphthol (S-M-1) with (S)-2,2′-binaphthyldiamine (S-M-2) via nucleophilic addition-elimination reaction, and the chiral polymer P-2 could be obtained by the reduction reaction of P-1 with NaBH₄. The fluorescence intensity of the chiral polymer P-1 exhibits gradual enhancement upon addition of (d)- or (l)-phenylalaninol and keeps nearly a linear correlation with the concentration molar ratios of (d)- or (l)-phenylalaninol. The value of enantiomeric fluorescence difference ratio (ef) is 6.85 for the chiral polymer on (d)-phenylalaninol. On the contrary, the chiral polymer P-2 shows no obvious fluorescence response toward either (d)- or (l)-phenylalaninol.     

Simultaneous kinetic resolution of chiral propylene oxide and propylene glycol in a continuous reactive distillation column

Traditionally kinetic resolutions are conducted by batch processing to recover one of the desired enantiomers of the racemate, while the product formed by the resolution is discarded due to its low purity. However, chiral materials are economically valuable and simultaneously conducting the reaction and separation, using reactive distillation, allows for both a reactant enantiomer and a product enantiomer to be recovered in high enantiomeric excess and yield. A feasible design of a continuous reactive distillation column is presented which performs a simultaneous kinetic resolution of racemic propylene oxide to produce both enantiomerically-pure propylene oxide and propylene glycol.     

Ce cooperated layered double oxide with enhanced base sites activity for the synthesis of polycarbonate diols

The development of highly efficient alkaline catalysts with abundant base sites is of paramount importance for the synthesis of polycarbonate diols (PCDLs). And the application of heterogeneous catalysts is an effective strategy to address the effect of residual catalysts on the quality of PCDLs. Here, Ce cooperated layered double oxide (LDO-Ce) was used as a catalyst for the preparation of PCDLs via transesterification between dimethyl carbonate (DMC) and 1,4-butanediol (BDO). CO₂ temperature-programmed desorption (CO₂-TPD) profiles demonstrated that the introduction of Ce led to an increase in strong base sites of LDO-Ce, thus endowing LDO-Ce with excellent catalytic performance. Besides, LDO-Ce possessed satisfactory specific surface area and pore size. A possible catalytic mechanism was proposed to illustrate the transesterification process. The effects of the reaction conditions on the hydroxyl value, yield, and BDO conversion were further investigated in detail. The yield of PCDLs with a hydroxyl value of 112.2 mg KOH/g (corresponding to a number average molecular weight [M_n] of 1000 g/mol) was 92.44% under its optimum reaction conditions (w (catalyst) = 0.5%, n(DMC)/n(BDO) = 1.25, T-_{transesterification} = 130°C, t-_{transesterification} = 5 h, T-_{polycondensation} = 170°C, t-_{polycondensation} = 4 h, P-_{polycondensation} = 10 kPa). Moreover, LDO-Ce was easily removed after the transesterification process (Step 1), ensuring the quality of PCDLs, and it was recycled three times without significant loss of catalytic activity.     

General approach to synthesis of chiral branched hydrocarbons in high configurational purity

Configurationally pure (>99.6%) -methylalkanoic acids have been employed to prepare chiral hydrocarbon semiochemicals. The stereoisomers of the following compounds were synthesized: 13-methylhentriacontane, 15-methyltritriacontane, and 15,19-dimethyltritriacontane. The first compound was identified earlier as a kairomone of the corn earworm while the other two are sex excitants of the stable fly. The methods described have broad applicability in asymmetric synthesis.     

水解动力学拆分合成手性环氧氯丙烷用催化剂研究

水解动力学拆分是目前合成手性环氧氯丙烷的有效方法。salen催化剂的应用使得该反应得到的手性环氧氯丙烷产率高且具有高光学纯度,因此,关于salen催化剂的研究得到广泛关注。综述了合适salen催化剂的研究发现和完善过程,提出了引入价廉、具有高催化活性和高重复利用性的催化剂仍是当前乃至今后该领域研究工作的重点。     

Yeast‐mediated enantioselective synthesis of chiral R‐(+)‐ and S‐(−)‐1‐phenyl‐1‐butanol from prochiral phenyl n‐propyl ketone in hexane–water biphasic culture

BACKGROUND: The hydrophobic phenyl n‐propyl ketone was used as a model compound to examine alcohol dehydrogenase activity in Saccharomyces cerevisiae mediated cell culture. Parameters such as pH, hexane‐to‐water volume percentage, and the amount of cofactor Zn²⁺ ion for either cell growth or reduction were studied to see their effect on the enantioselectivity toward the product R‐(+)‐ or S‐(?)‐1‐phenyl‐1‐butanol. RESULTS: The pH for cell growth in aqueous culture was 7.0, while the pH for reduction in the aqueous portion of the biphasic culture was 5.0. Without Zn²⁺ ion the biphasic cultures of middle to high hexane‐to‐water volume percentage exhibited an R‐(+)‐1‐phenyl‐1‐butanol enantiomeric excess of 53.7% to > 99%. Without Zn²⁺ ion the biphasic cultures at low hexane‐to‐water volume percentage possessed an S‐(?)‐1‐phenyl‐1‐butanol enantiomeric excess of 14.5–46.5%. Exclusively, the enantioselectivity for biphasic cultures containing Zn²⁺ ion was an S‐(?)‐1‐phenyl‐1‐butanol enantiomeric excess of 27.5% to > 99%. Reduction mediated in aqueous culture with varied amount of Zn²⁺ ion by the yeast Candida utilis also showed an S‐(?)‐1‐phenyl‐1‐butanol enantiomeric excess of 79.2–95.4%. CONCLUSION: The enantioselectivity of S. cerevisiae mediated biphasic culture reduction of phenyl n‐propyl ketone can be manipulated through the cofactor Zn²⁺ ion and the hexane volume percentage of the biphasic culture. Copyright © 2008 Society of Chemical Industry