Asymmetric Intramolecular C?H Insertion of α‐Diazoacetamides in Water by Dirhodium(II) Catalysts Derived from Natural Amino Acids

The asymmetric dirhodium(II)‐catalyzed intramolecular C H insertion of α‐diazo acetamides in water is described for the first time. The use of natural α‐amino acids as chiral ligands allowed the preparation of novel dirhodium(II) homochiral complexes by a simple procedure consisting of the in situ ligand exchange starting from dirhodium tetraacetate. The catalytic system was further reused up to 7 cycles and β‐lactams were obtained in good yields and enantiomeric excess.     

手性受载试剂及其在不对称合成中的应用

各种手性受载试剂的制备及其在不对称反应中的应用，例如加成反应、还原反应、甲酰化反应、氨基酸的合成、氧化偶合反应和环氧化反应等。其中大多数反应的对映超量都较高。     

Resolution by Preferential Crystallization of Proxyphylline by Using Its Salicylic Acid Monohydrate Co-Crystal

The monohydrated co-crystal composed of the chiral active pharmaceutical ingredient proxyphylline, salicylic acid, and water was successfully resolved by preferential crystallization from a water/ethanol mixture. To the best of our knowledge, this is the first report of preferential crystallization applied to such a system and the results reveal that unusually high enantiomeric excess values can be attained in the mother liquor. These robust and reproducible results underline the potential of preferential crystallization to resolve co-crystal systems.     

Heterocyclic quinones. VIII. Synthesis and spectra of new carbazoloquinone derivatives of naturally occurring amino acids

Fifteen naturally occurring amino acids representing basic, neutral and acidic members were interacted with 4,4′-dimethoxydiquinone (I). Basic amino acids reacted readily to give amino acid substituted carbazoloquinones (III), while neutral and acidic amino acids reacted only after addition of an acid binding agent. Using an excess of any of the amino acids resulted in the substitution of the quinonoid methoxyl group in compounds (III) by an amino acid moiety. In the case of basic amino acids, this substitution reaction was preferentially influenced by a terminal amino or guanidino amino rather than by an α-amino group. Moreover, basic amino acids could be reacted with two moles of (I) to produce dicarbazoloquinones (X). The i.r. and u.v.-visible spectra of the various carbazoloquinone products were determined and discussed.     

Preparation of schiff base adducts of phosphatidylcholine core aldehydes and aminophospholipids, amino acids, and myoglobin

We have prepared Schiff base adducts of the core aldehydes of phosphatidylcholine and aminophospholipids, free amino acids, and myoglobin. The Schiff bases of the ethanolamine and serine glycerophospholipids were obtained by reacting sn-1-palmitoyl(stearoyl)-2-[9-oxo]nonanoyl-glycerophosphocholine (PC-Ald) with a twofold excess of the aminophospholipid in chloroform/methanol 2∶1 (vol/vol) for 18 h at room temperature. The Schiff bases of the amino acids and myoglobin were obtained by reacting the aldehyde with an excess of isoleucine, valine, lysine, methyl ester lysine and myoglobin in aqueous methanol for 18 h at room temperature. Prior to isolation, the Schiff bases were reduced with sodium cyanoborohydride in methanol for 30 min at 4°C. The reaction products were characterized by normal-phase high-performance liquid chromatography and on-line mass spectrometry with electrospray ionization. The amino acids and aminophospholipids yielded single adducts. A double adduct was obtained for myoglobin, which theoretically could have accepted up to 23 PC-Ald groups. The yields of the products ranged from 12 to 44% for the aminophospholipids and from 15–57% for the amino acids, while the Schiff base of the myoglobin was estimated at 5% level. The new compounds are used as reference standards for the detection of high molecular weight Schiff bases in lipid extracts of natural products. Based on presentation at the AOCS Annual Meeting & Expo in Indianapolis, Indiana, April 28–May 1, 1996.     

Enantioselective hydrogenation of trifluoroacetophenone over cinchonidine-modified platinum

The enantioselective hydrogenation of 2,2,2-trifluoroacetophenone to (R)-1-phenyl-2,2,2-trifluoroethanol represents a new application of supported Pt catalysts modified with cinchona alkaloids. Heat treatment of a 5 wt% Pt/alumina catalyst at 400°C in flowing hydrogen, followed by an air-treatment of the reaction mixture before the hydrogenation reaction improved the enantiomeric excess by a factor of 2.5. Traces of water in apolar medium, high trifluoroacetophenone and moderate cinchonidine concentrations were also advantageous for enantiodifferentiation. Both reaction rate and enantiomeric excess increased during the initial transient period of the reaction, below 10% conversion.     

Enantioselective Polymeric Composite Membrane for Optical Resolution of Racemic Mixtures of α-Amino Acids

The optical resolution of racemic mixtures of α-amino acids was performed using novel enantioselective polymer membrane to obtain optically pure isomers. The novel membranes were prepared by polymerizing a mixture of D-arginine, piperazine, and trimesoyl chloride in-situ interfacial on polysulfone ultrafiltration membrane. ATR-FTIR spectroscopy, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM) techniques were used to characterize the membranes and co-relate membrane morphology with membranes performance. The optical resolution performance of the membrane process was quantified by performing optical resolution of racemic arginine and asparagine in pressure driven separation mode at low pressures. The influence of monomers concentrations and their ratio in the polymerizing mixture on the flux and enantioseparation was studied. The observations indicated >91 percent enantiomeric excess (>91% ee) of L-arginine and >56 percent enantiomeric excess (>56% ee) of L-asparagine in the permeate of the racemic feed. The membrane prepared using equiconcentrated (2%) solutions of D-arginine, piperazine, and trimesoyl chloride exhibited highest enantiomeric excess (91%). At 91% ee the separation factor (α) for L-arginine was approximately 16.     

Ultra-trace Analysis of Enantiomeric Impurities in Proteinogenic N-Fmoc-Amino-acid Samples on Cinchona Alkaloid-based Chiral Stationary Phases

The enantiomeric purity of N_α-Fmoc-protected amino acids is crucial from the viewpoint of peptide synthesis; therefore, a sensitive high-performance liquid chromatographic protocol was developed for the identification and quantification of enantiomeric impurities of commercially available N_α-Fmoc-protected amino acids on Cinchona alkaloid quinine- and quinidine-based weak anion exchanger-type chiral stationary phases. In the course of the evaluation of the chiral chromatographic method, the effect of the mobile phase composition, nature, and concentration of different additives were optimized. The specific phenomenon that quinine- and quinidine-based chiral stationary phases behave as pseudo-enantiomers permits that the sequence of elution of the enantiomers might be reversed by simple column switching. This is quite advantageous as regards the separation of the minor component in the presence of the major one. The method developed permits detection of less than 0.01 % enantiomeric impurity in the presence of the major enantiomer.     

Enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester using cinchonine-modified Pd/TiO2 catalysts

The enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester (NADPME) to N-acetyl phenylalanine methyl ester is investigated using cinchonine-modified Pd/TiO₂ catalysts. The catalysts were prepared using deposition–reduction and wet impregnation methods and were evaluated for reaction using methanol as solvent with various cinchonine/NADPME molar ratios. Enantioselectivity was sensitive to this ratio and comparison with Pd/γ-Al₂O₃ showed that the Pd/TiO₂ gave marginally higher enantioselectivity when tested under comparable conditions. The effect of Pd loading and dispersion was investigated and the maximum enantiomeric excess observed was dependent on the dispersion; the role of the Pd particle size is discussed in the context of cinchonine adsorption. The reactions were carried out in solvents (methanol and dimethyl formamide) and mixed solvents (methanol–water and dimethyl formamide–water); the enantiomeric excess was significantly enhanced using dimethyl formamide. The addition of water does not have a significant effect for the Pd/TiO₂ catalysts. In this paper we report the highest enantiomeric excess for the hydrogenation of a prochiral ester using an immobilised catalyst.     

使用手性相转移催化剂不对称诱导(±)-1,3-二甲基-5-甲氧基氧化吲哚的碳烷基化反应

报道了９种手性季铵盐催化１，３－二甲基－５－甲氧基氧化吲哚的不对称碳烷基化反应。通过研究催化剂的不同结构、溶剂、温度、碱对产物光学活性的影响，讨论了不对称诱导机理。确定了产物绝对构型和对映体过量。     

Stereochemical integrity of oxazolone ring-containing jadomycins

The jadomycins are a series of natural products produced by Streptomyces venzuelae ISP5230 in response to ethanol shock. A unique structural feature of these angucyclines is the oxazolone ring, the formation of which is catalyzed by condensation of a biosynthetic aldehyde intermediate and an amino acid. The feeding of enantiomeric forms of alpha-amino acids indicates that the amino acid is incorporated by S. venezuelae ISP5230 without isomerization at the alpha-carbon. The characterization of the first two six-membered E-ring-containing jadomycins is reported. These precursor-directed biosynthesis studies indicate flexibility in the acceptor substrate specificity of the glycosyltransferase, JadS. Analysis of cytotoxicity data against two human breast cancer cell lines indicates that the nature of the substitution at the alpha-carbon, rather than the stereochemistry, influences biological activity.     

Chiral resolution of differently substituted racemic acetyl‐1‐phenyl ethanol using lipase from Bacillus subtilis

In the present investigation a Lipase producing strain, Bacillus subtilis (MTCC‐121) was grown on various media containing different sources of carbon, nitrogen and other nutrients. The best media found for the production of lipase was M2 media containing 0.4% peptone, 0.2% beef extract and 1% NaCl. Lipase produced from this culture was used for the kinetic resolution of racemic acetyl‐1‐phenyl ethanol and its derivatives, which are important as chiral auxiliaries and intermediates in the synthesis of natural products, pharmaceuticals and agrochemicals. The lipase resolved these substrates after 48 h with enantiomeric excess of 90–98% and conversion 40–48%. Copyright © 2010 Society of Chemical Industry     

β-氨基酸消旋体的合成与手性分离

光学纯β-氨基酸是合成拟多肽和β-内酰胺类抗生素等药物的重要中间体,其制备方法通常涉及多步反应,原料昂贵,操作复杂且产率较低。以醛、丙二酸和铵盐为原料,采用“一锅法”合成了5种β-氨基酸消旋体。应用手性配体交换色谱对所合成的氨基酸消旋体进行拆分,获得了光学纯β-氨基酸对映体。结果表明基于“一锅法”合成β-氨基酸消旋体和手性配体交换色谱分离对映体的制备方法具有操作简便,成本低廉,产率较高的特点,适合用于药物高通量筛选不同结构β-氨基酸对映体的快速制备。     

Preparative Chiral Liquid Chromatography for Enantiomeric Separation of Pheromones

Cellulose triacetate was investigated as a chiral stationary phase for preparatively separating the enantiomers of lineatin, frontalin, exo-brevicomin, endo-brevicomin, verbenone, (E)-conophthorin, and grandisol. Tens of milligrams of both enantiomers were efficiently prepared in high percentage enantiomeric excess from one injection of each compound except grandisol. We prepared grandisyl acetate, benzoate, and 4-bromobenzoate to determine if derivatization of the free alcohol might improve separation. Of these, grandisyl 4-bromobenzoate provided the best separation but was still not very well resolved. Preparative separation of enantiomers on cellulose triacetate is a viable alternative to stereoselective synthesis when semiochemicals of very high enantiomeric purity are required for biological testing.     

Kinetic resolution of chiral hydroperoxides via Sharpless Epoxidation

The kinetic resolution of tertiary hydroperoxides via catalytic Sharpless epoxidation with various allylic alcohols has been investigated. By using 1-cyclohexyl-1-phenylethyl hydroperoxide an enantiomeric excess (e.e.) of up to 29% of the resolved hydroperoxide has been observed at a consumption of the racemic hydroperoxide of nearly 50%. The e.e. can be increased, however, only by raising the hydroperoxide consumption.     

近临界水中水解鱼蛋白制备氨基酸

The hydrolysis technology and reaction kinetics for amino acids production from fish proteins in subcritical water reactor without catalysts were investigated in a reactor with volume of 400 ml under the conditions of reaction temperature from 180-320℃, pressure from 5-26 MPa, and time from 5-60 rain. The quality and quantity of amino acids in hydrolysate were determined by bioLiquid chromatography, and 17 kinds of amino acids were obtained. For the important 8 amino acids, the experiments were conducted to examine the effects of reaction temperature, pressure and time on amino acids yield. The optimum conditions for high yield are obtained from the experimental results. It is found that the nitrogen and carbon dioxide atmosphere should be used for leucine, isoleucine and histidine production while the air atmosphere might be used for other amino acids. The reaction time of 30 rain and the experimental temperature of 220℃, 240℃ and 260℃ were adopted for reaction kinetic research. The total yield of amino acids versus reaction time have been examined experimentally. According to these experimental data and under the condition of water excess, the macroscopic reaction kinetic equation of fish proteins hydrolysis was obtained with the hydrolysis reaction order of 1.615 and the rate constants being 0.0017, 0.0045 and 0.0097 at 220℃, 240℃ and 260℃ respectively. The activation energy is 145.1 kJ·mol^- 1.     

近临界水中鱼肉水解制备氨基酸的反应动力学

利用鱼肉蛋白制备氨基酸不但具有经济效益,而且为生物质资源高效利用提供技术支持。采用HL-F(0.2 L+1.5 MG)/30 MPa-IIA超临界水反应装置,在无催化剂、反应温度分别为220,240,260℃,反应时间为30 min条件下,对鱼肉蛋白在近临界水中水解为氨基酸的反应动力学进行了实验研究。用AAA-Direct氨基酸分析仪测定不同反应时间中氨基酸总产率,以酸水解鱼肉蛋白得到的氨基酸量为完全水解标准。在水过量的情况下,得到了鱼肉蛋白水解率宏观反应动力学方程。结果表明鱼肉蛋白水解动力学的级数为1.614 7,220,240,260℃下的反应速率常数分别为0.001 7,0.004 5,0.009 7,活化能为145.125 kJ/mol,前置因子A为9.475 7×109,为工业化生产提供了基础数据。     

Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives

The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of α‐phenylalanine to β‐phenylalanine, an important step in the biosynthesis of the N‐benzoyl phenylisoserinoyl side‐chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)‐cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring‐substituted (E)‐cinnamic acids can serve as a substrate in PAM‐catalysed ammonia addition reactions for the biocatalytic production of several important β‐amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non‐natural aromatic α‐ and β‐amino acids in excellent enantiomeric excess (ee >99 %). The internal 5‐methylene‐3,5‐dihydroimidazol‐4‐one (MIO) cofactor is essential for the PAM‐catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.     

Asymmetric Borane Reduction of Prochiral Ketones Catalyzed by α,α-Disubstituted Aziridinemethanols

A series of novel α,α-disubstituted aziridinemethanols have been developed for the enantioselective reduction of ketones in refluxing tetrahydrofuran. The optically active secondary alcohol products were obtained in good enantiomeric excess (~96.8%) and excellent yields. The results showed that the substituent groups on the hydroxyl-bearing carbon of aziridinemethanols obviously affected the enantioselectivity.     

Enantioselective permeation of α‐amino acid optical isomers through crosslinked sodium alginate membranes

A pressure‐driven separation process, using self‐supporting crosslinked sodium alginate (SA) membranes with different swelling indices, enabled the optical resolution of α‐amino acids, including the optical isomers of tryptophan and tyrosine. The SA membranes were prepared by the casting and drying of SA solutions on an acryl plate, followed by crosslinking with glutaraldehyde. They were characterized with analytical methods, such as Fourier transform infrared and swelling index measurements. During optical resolution with the SA membranes, the effects of experimental factors were studied, such as the concentration of the feed solutions, the operating pressure, and the degree of crosslinking of the membranes. When an SA membrane with a swelling index of 80% was used, a good optical resolution of tryptophan isomers was obtained: an enantiomeric excess of 54.0% and a flux of 24.8 mg/m² h. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3046–3051, 2003