环氧化合物水解酶的研究进展

环氧化合物水解酶(Epoxidehydrolase,EHs,EC3.3.2.3),是一组催化环氧化合物水解为相应邻位二醇的酶类,在哺乳动物、植物、昆虫和微生物体内广泛存在.由于环氧化合物的环氧乙烷部分是一个亲电的三元环,其C-O键的极性很强,能与体内包括DNA和蛋白质在内的多种活性物质发生反应,具有较强的毒性,甚至致癌性.研究表明,有两种酶涉及到环氧化合物的脱毒过程,其一为谷胱甘肽转移酶,该酶是一种广谱性脱毒酶,具有清除自由基的功能,但目前仅发现少数来源细菌的谷胱甘肽转移酶能降解模式环氧化合物;其二为环氧化合物水解酶,该酶能选择性地降解体…     

有机溶剂/缓冲液双相体系中绿豆环氧化物水解酶催化环氧苯乙烯不对称水解反应

研究了有机溶剂/缓冲液双相体系中绿豆环氧化物水解酶高立体选择性地催化外消旋环氧苯乙烯水解生成(R)-苯基乙二醇反应.结果表明,与单水相反应体系相比,有机溶剂/缓冲液双相反应体系不仅有效地抑制环氧苯乙烯的非酶水解反应,而且明显提高底物的浓度,产物的收率和ee值更高.在所考察的不同有机溶剂中,正己烷不仅能较好地溶解底物,而...     

手性邻二醇－－（2S，3R）－1，2，3－丁三醇－1－对甲苯磺酸酯的不对称合成

以（E）－2－丁烯－1－醇为原料经不对称环氧化反应合成2，3－环氧醇（1） 。该环氧醇的对甲苯磺酸酯对映选择性酸水解开环制备手性邻二醇（2）(95％ee)。     

毛白杨环氧水解酶的异源表达及其在催化拆分手性环氧化物中的应用

对已公布的全基因组进行检索发现,杨树(Populus tomentosa)至少含有24个预测为可溶性环氧水解酶的基因.从中选取了7个可能的环氧水解酶基因进行克隆,通过扩增得到其中5个毛白杨(Populus tomentosa Carr)环氧水解酶基因.序列分析显示,它们与已克隆的巨大芽胞杆菌环氧水解酶的同源性仅为24%～26%.对该系列基因进行了在E.coli中的异源表达,并将得到的5个环氧水解酶(PTEH1～5)用于缩水甘油苯基醚和对硝基苯乙烯氧化物的酶促水解反应.结果发现,其中3个重组酶具有显著的环氧水解酶活性.进一步研究表明,PTEH1和PTEH2对于缩水甘油苯基醚显示了一定的反常规的(R)-选择性,而PTEH5则优先水解(S)-构型的缩水甘油苯基醚.因此,毛白杨中环氧水解酶表现出多样性.     

三级环氧醇与PCC的非对映性氧化反应研究

报道一类新颖的氯铬酸吡啶盐(PCC)与三级环氧醇的非对映选择性氧化反应,就反应的立体选择性、化学选择性和可能的反应机理进行了讨论。该反应不仅可用于制备手性的三级环氧醇,同时还可以用于合成含有手性季碳中心的1,3-二酮。     

三级环氧醇与PCC的非对映性氧化反应研究

报道一类新颖的氯铬酸吡啶盐(PCC)与三级环氧醇的非对映选择性氧化反应,就反应的立体选择性、化学选择性和可能的反应机理进行了讨论。该反应不仅可用于制备手性的三级环氧醇,同时还可以用于合成含有手性季碳中心的1,3-二酮。     

1,3-手性转移反应的研究 (4R)-和(4S)-4-甲基(E)-2-辛烯醇的合成

以手性辛烯二醇双酯与甲基锂铜反应, 经1,3手性转移, 分别生成立体选择性高的(4R)和(4S)-4-甲基-辛烯醇酯。     

绞股蓝皂苷酸水解次生苷元的分离与鉴定

绞股蓝皂苷用5%硫酸水解,生成的次生皂苷元除已报道的人参二醇和2α-羟基人参二醇之外,尚分离到(20R.25S)-12β,25-环氧20,26-环达玛烷-2α,3β-二醇一新化合物.其结构经波谱分析和X射线衍射鉴定,确证20-C和25-C手性中心的绝对构型分别为R和S型.     

1,3-手性转移反应的研究 (4R)-和(4S)-4-甲基(E)-2-辛烯醇的合成

以手性辛烯二醇双酯6和7与甲基锂铜反应,经1,3手性转移,分别生成立体选择性高的(4R)和(4S)-4-甲基-辛烯醇酯8a 和9a     

用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇

以D-甘露醇为原料合成(R)-(+)-缩水甘油1。该环氧化合物的亲核开环反应为高立体选择性地(93%-96%e.e.)制备各种手性连二醇提供了一条简便途径。     

Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol

A chiral cobalt(III) complex (1e) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R-(-)-1,2-diaminocyclohexane with trigol bis-aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47% with respect to the epoxides, 53% with respect to the diols) and high enantioselectivity (ee>99% for the epoxides, up to 96% for the diols) were achieved in 2.5-16 h. The Co(III) macrocyclic salen complex (1e) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)-mexiletine and (S)-propranolol.     

Development of heterogeneous olympic medal metal nanoparticle catalysts for environmentally benign molecular transformations based on the surface properties of hydrotalcite

In this review, we describe the development by our research group of highly functionalized heterogeneous Olympic medal metal (gold, silver, and copper) nanoparticle catalysts using hydrotalcite as a support, aimed towards Green and Sustainable Chemistry. Olympic medal metal nanoparticles can cooperate with the basic sites on the hydrotalcite surface, providing unique and high performance catalysis in environmentally-benign organic transformations such as aerobic oxidation of alcohols, lactonization of diols and selective deoxygenation of epoxides and nitro aromatic compounds.     

Hydrogen‐Bond‐Mediated Asymmetric Catalysis

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single‐step and multiple‐step cascade reactions. These functionalities, which have the ability to afford efficient H‐bond activation of electrophiles including C?O, C?N, aziridines, and epoxides, have established their status as “privileged” functional groups in the design of organocatalysts.     

Nitrite-mediated hydrolysis of epoxides catalyzed by halohydrin dehalogenase from Agrobacterium radiobacter AD1: a new tool for the kinetic resolution of epoxides

Halohydrin dehalogenase obtained from Agrobacterium radiobacter AD1, has been tested for the nitrite-mediated ring opening of epoxides. This reaction mainly leads to the formation of unstable hydroxynitrite ester intermediates, which can be further hydrolyzed to the corresponding diols. This conversion proceeds with high enantioselectivity and high regioselectivity towards styrene oxide derivatives. It has been concluded that halohydrin dehalogenase can serve as an attractive alternative to epoxide hydrolases in the preparation of enantiopure epoxides by kinetic resolution.     

Zirconyl triflate, [ZrO(OTf)2], as a new and highly efficient catalyst for ring-opening of epoxides

A highly efficient method for the ring opening of epoxides catalyzed by ZrO(OTf)₂ was adopted. This catalyst efficiently catalyzed alcoholysis, acetolysis and hydrolysis of epoxides and the corresponding alkoxy alcohols, acetoxy alcohols and 1,2- diols were obtained in excellent yields. Conversion of epoxides to 1,2-diacetetes, thiiranes and 1,3-dioxolanes was also performed in the presence of catalytic amounts of ZrO(OTf)₂, and the corresponding products were obtained in high to excellent yields. The high catalytic activity of ZrO(OTf)₂ is due to the replacement of Cl with OTf, which makes the ZrO(OTf)₂ as efficient Lewis acid.     

Asymmetric Hydrolytic Kinetic Resolution with Recyclable Macrocyclic CoIII–Salen Complexes: A Practical Strategy in the Preparation of (R)‐Mexiletine and (S)‐Propranolol

A chiral cobalt(III) complex ( 1 e ) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R‐(?)‐1,2‐diaminocyclohexane with trigol bis‐aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1 e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47 % with respect to the epoxides, 53 % with respect to the diols) and high enantioselectivity (ee>99 % for the epoxides, up to 96 % for the diols) were achieved in 2.5–16 h. The Co^III macrocyclic salen complex ( 1 e ) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)‐mexiletine and (S)‐propranolol.     

Co(Ⅲ)(Salen)催化的外消旋环氧化合物不对称开环

用较易得到的(R,R)-1,2-二苯基乙二胺(DPEDA)与-2-羟基-5-甲基-3-叔丁基苯甲醛缩合,得到手性Salen,再与Co络合,氧化后得到Salen型手性催化剂(R,R)-2。(R,R)-2可催化外消旋环氧化物的动力学水解拆分,所得手性二醇和手性环氧化合物对映体过量最高分别可达99%和92%。     

用Sharpless不对称双羟化反应合成手性β-氨基醇

以烯烃为原料合成了一组对映体纯的β-氨基醇．在手性配体1,4-双(9-O-奎宁)-2,3-二氮杂萘[(QN)₂PHAL]存在下, 通过烯烃的Sharpless不对称双羟化、环化、亲核开环和催化氢化等步骤方便地合成了手性β-氨基醇. 从环氧化物到氨基醇的总产率为89%～94%, β-叠氮醇和β-氨基醇的光学纯度高达90%～99% ee. 同时考察了影响环氧化物开环的各种因素．     

不具C_2对称轴的Co(III)(Salen)催化的末端环氧化合物的水解拆分

用 (S) 3 甲基 1,2 丁二胺或 (R) 1,2 丙二胺为原料与 2 羟基 5 甲基 3 叔丁基苯甲醛缩合 ,得到不具C2 对称轴的手性Salen ,与Co(II)络合并氧化后得到 4a或 4b .4a和 4b成功地应用于外消旋末端环氧化合物的水解拆分 ,取得了较好的产率 ,但产物的对映体过量值较低     

Preparation and synthetic application of 2-bromoallyltrimethylsilane as a 1-hydroxymethylvinyl anion equivalent

The 1-trimethylsilylmethylvinyl group, as a 1-hydroxymethylvinyl equivalent, was readily introduced to epoxides with the corresponding Grignard reagent derived from 2-bromoallyltrimethylsilane. Obtained 2-(2-hydroxy-ethyl)-allylsilanes were converted to α-methylene-γ-lactones via diols.