手性源、手性池和手性农药中间体的开发研究

介绍手性源、手性池和手性分子化合物的基本概念;由手性池化合物制备手性衍生物;比较了手性化合物生物加工与化学加工过程的优、缺点,寻求高效、经济和最合理的综合工艺流程。     

Enantioselective synthesis of chiral sulfinates using chiral diamines

The reaction of p-toluenesulfinyl chloride with alcohols in the presence of chiral diamines was examined. Chiral sulfinates were obtained in good yields with enantioselectivity up to 76% ee.     

Enantioselective separation of cyclic chiral ketones and their corresponding diastereomeric alcohols by HPLC on chiral and chiral/chiral coupled stationary phases

Enantioselective HPLC methods have been developed for the resolution of (RS)-2-phenylcyclohexanone (compound 1) and (RS)-2-phenyltetrahydropyran-4-one (compound 4) and the diastereoselective and enantioselective separations of their respective cis- and trans-alcohols; reduction of compound 1 yields trans- and cis-2-phenyl-1-cyclohexanol (compounds 2 and 3, respectively) and reduction of compound 4 yields trans- and cis-2-phenyl-tetrahydropyran-4-ol (compounds 5 and 6, respectively). Compounds 1, 2, and 3 were stereochemically resolved using a chiral stationary phase (CSP) based upon amylose tris(3,5-dimethylphenyl carbamate) coated on 10 μm silica-gel (Chiralpak AD-CSP). Compounds 4, 5, and 6 were stereochemically resolved on a coupled column system where a column containing a CSP based upon cellulose tris(3,5-dimethylphenyl carbamate) coated on 5 μm silica (Chiralcel OD-H-CSP) was coupled in series to the AD-CSP. The strategy employed in the identification of the peaks in the respective chromatograms is also discussed in this presentation. Chirality 8:551–555, 1996. © 1997 Wiley-Liss, Inc.     

The development of biphasic chiral recognition in chiral separation

In chiral separation, enantioseparation factor is an important parameter which influences the resolution of enantiomers. In this current overview, a biphasic chiral recognition method is introduced to the readers. This method can significantly improve the enantioseparation factor in two‐phase solvent through adding lipophilic and hydrophilic chiral selectors which have opposite chiral recognition ability to organic and aqueous phases, respectively. This overview presents the development and applications of biphasic chiral recognition in liquid‐liquid extraction and counter current chromatography. It mainly focuses on the topics of mechanism, advantages and limitations, applications, and key factors of biphasic chiral recognition. In addition, the future outlook on development of biphasic chiral recognition also has been discussed in this overview.     

Mechanism of chiral asymmetry generation by chiral autocatalysis in the preparation of chiral octahedral cobalt complex

Chiral asymmetry generation, the predominant production of one enantiomer in a non-chiral environment, could occur in the production of the chiral complex cis-[CoBr(NH₃)(en)₂]Br₂ by the reaction of [Co(H₂O)₂{(OH)₂Co(en)₂}₂](SO₄)₂ with ammonium bromide in an aqueous medium. The main kinetic steps in the reaction system have been determined. During the reaction, the product crystallizes at an early stage. When a very small amount of crystalline enantiomer was added to the reaction system at an early stage, the same enantiomer was produced preferentially; in addition, the enantiomeric excess of the product increased with increasing the stirring rate. Thus, it seems that each enantiomer generates chiral crystals that could self-replicate through secondary nucleation when the solution is stirred; these crystals in turn enhance the production of the same enantiomer. With a computer code that simulates such a kinetic mechanism, it is shown that enantiomeric excess observed in the experiments could be reproduced. Chirality 10:343–348, 1998. © 1998 Wiley-Liss, Inc.     

Direct screening of chiral discrimination abilities of chiral hosts using mass spectrometry

A simultaneous estimation of the chiral discrimination abilities of several chiral hosts was demonstrated on the basis of one mass spectrum. The chiral host mixture, including H(1), H(2), H(3) ..., and H(m) (m: number of hosts) was prepared by etherification of several chiral alcohols with bistosylate of diethylene glycol. An equimolar mixture of a deuterium-labeled (S)- and unlabeled (R)-enantiomer of an amino acid isopropyl ester hydrochloride (G(S-dn) (+)Cl(-) and G(R) (+)Cl(-), n: number of deuterium atoms) was added to the chiral host mixture, and the FAB mass spectrum was measured to evaluate the chiral discrimination ability of each host in the mixture without isolation. The chiral discrimination ability of each host toward the guest is represented by the relative peak intensity of the diastereomeric complex ion pair, I(H(m) + G(R)((+)/I(H(m) + G(S-dn))(+) (=I(R)/I(S-dn) value). Several new hosts showed good chiral discrimination toward the guest.     

Hydrobenzoin-based rigid chiral polymer

We prepared a rigid, chiral polymer (1) from optically active hydrobenzoin-based subunits. Nonracemic monomer units 6 and 8 were prepared by asymmetric dihydroxylation (AD) methodology and polymerization was carried out under Sonagashira coupling conditions. Polymer 1 was obtained in good yield with a molecular weight M(n) = 5,100 (PDI = 2.3). Modeling suggests that polymer 1 could form a stable helical mainchain conformation in solution or the solid state. The chiroptical data of the polymer and a low-molecular weight model compound (9) are compared.     

Self‐assembly and chiral recognition of quartz crystal microbalance chiral sensor

A novel chiral sensor based on the self‐assembled monolayer of (6^A‐ω‐mercaptoethylureado‐6^A‐deoxy)heptakis(2,3‐di‐o‐phenylcarbamoyl)‐6^B, 6^C, 6^D, 6^E, 6^F, 6^G‐ hexa‐o‐phenylcarbamoyl‐β‐cyclodextrin (Ph‐β‐CD‐SH) on a quartz crystal transducer for chiral recognition was set up. (R,S)‐(±)‐(3‐Methoxyphenyl)ethylamine were recognized by this QCM chiral sensor with a QCM chiral discrimination factor of 1.33. Furthermore, UV spectroscopy was used to investigate the mechanism of host‐guest interactions between (6^A‐azido‐6^A‐deoxy)heptakis(2,3‐di‐o‐phenylcarbamoyl)‐6^B, 6^C, 6^D, 6^E, 6^F, 6^G‐hexa‐o‐phenylcarbamoyl‐β‐cyclodextrin (Ph‐β‐CD) and (R,S)‐(±)‐(3‐methoxyphenyl) ethylamine. The UV discrimination factor was determined to be 0.066. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Enantiomer self-disproportionation and chiral stationary phase based selective chiral separation of organic compounds

In modern chromatography, chiral stationary phase (CSP) and enantiomer self-disproportionation (ESD) are new inventions of packing material offer a guarantee for a successful enantiomeric separation. All CSPs were synthesized by chemical bonding of the relevant organic moieties onto a porous parent silica material for the separation of various racemic mixtures whereas achiral silica matrix was used for separation of non-racemic mixtures in ESD. Our present study provides to establish an understanding on the entire enantio-selective profile of amino alcohol based CSP as well as ESD and their precise utilization for high success rates for selective enantiomer separation with its appropriateness.     

Phospholipids chiral at phosphorus. Synthesis of chiral phosphatidylcholine and stereochemistry of phospholipase D

Chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphocholines (DPPC) with known configuration were synthesized by N-methylation of chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE). Transphosphatidylation of (RP)- and (SP)-[18O]DPPC catalyzed by phospholipase D from cabbage gave (RP)- and (SP)-[18O]DPPE, respectively, as indicated by 31P nuclear magnetic resonance (NMR) analysis of [18O]DPPE. Therefore, phospholipase D catalyzes transphosphatidylation with overall retention of configuration at phosphorus. The steric course of hydrolysis of DPPC catalyzed by the same enzyme was elucidated by the following procedures. Hydrolysis of (RP)-[17O, 18O]DPPC by phospholipase D gave 1,2-dipalmitoyl-sn-glycero-3-[ 16O , 17O, 18O]phosphate ( [ 16O , 17O, 18O] DPPA ) with unknown configuration. The latter compound was then converted to 1-[ 16O , 17O, 18O]phospho-(R)-propane-1,2-diol by a procedure involving no P-O bond cleavage [ Bruzik , K., & Tsai, M.-D. (1984) J. Am. Chem. Soc. 106, 747-754]. The configuration of the phosphopropane -1,2-diol was determined as RP by 31P NMR analysis following ring closure and methylation [ Buchwald , S. L., & Knowles, J. R. (1980) J. Am. Chem. Soc. 102, 6601-6603]. The results indicated that hydrolysis of DPPC catalyzed by phospholipase D also proceeds with retention of configuration at phosphorus. Our results therefore support a two-step mechanism involving a phosphatidyl-enzyme intermediate in the reactions catalyzed by phospholipase D from cabbage.     

Probability rule for chiral recognition

Molecular Chirality is of central interest in biological studies because enantiomeric compounds, while indistinguishable by most inanimate systems, show profoundly different properties in biochemical environments. Enantioselective separation methods, based on the differential recognition of two optical isomers by a chiral selector, have been amply documented. Also, great effort has been directed towards a theoretical understanding of the fundamental mechanisms underlying the chiral recognition process. Here we report a comprehensive data examination of enantio separation measurements for over 72000 chiral selector-select and pairs from the chiral selection compendium CHIRBASE. The distribution of alpha = k'(D)/k'(L) values was found to follow a power law, equivalent to an exponential decay for chiral differential free energies. This observation is experimentally relevant in terms of the number of different individual or combinatorial selectors that need to be screened in order to observe alpha values higher than a preset minimum. A string model for enantiorecognition (SMED) formalism is proposed to account for this observation on the basis of an extended Ogston three-point interaction model. Partially overlapping molecular interaction domains are analyzed in terms of a string complementarity model for ligand-receptor complementarity. The results suggest that chiral selection statistics may be interpreted in terms of more general concepts related to biomolecular recognition.     

HPLC with carbohydrate carbamate chiral phases: Influence of chiral phase structure on enantioselectivity

The enantioselective resolution of trans-stilbene oxide and of 23 chiral sulfoxides was investigated on cellulose and amylose tris(arylcarbamate) stationary phases coated on aminopropylated 7 μm spherical silica with 500 Å diameter pores. Cellulose tris-(3,5 dimethylphenylcarbamate) showed good resolving power for many of the sulfoxides and amylose tris-(3,5 dimethoxyphenylcarbamate) showed advantages for the resolution of certain sulfoxides which were not separated on other phases. © 1994 Wiley-Liss, Inc.     

Conditions for chiral asymmetry generation in the preparation of the chiral octahedral cobalt complex

We have reported that the random chiral asymmetry generation, which is a spontaneous preferential generation of one enantiomer, was observed in the synthesis of a chiral octahedral cobalt complex, cis-[CoBr(NH(3))(en)(2)]Br(2). In this article, we review our studies to explain in this system the autocatalytic growth of small enantiomeric excess that arises due to statistical fluctuations. One important experimental finding was that the rate of chiral autocatalysis increased with increasing the degree of supersaturation. Furthermore, our numerical simulation indicates that even small inhomogeneities in the reaction system may play a significant role because their effect is amplified by the autocatalytic reaction under appropriate conditions. In a small volume, fluctuations in concentration can grow if the autocatalytic growth overcomes the diffusional loss of the excess concentration from this volume. This may makes the enantiomeric excess of the chiral complex randomly fluctuate from run to run.     

A fluorescent chiral chemosensor for the recognition of the two enantiomers of chiral carboxylates

A new 7-nitrobenz-2-oxa-1,3-diazole (NBD)-based fluorescent chiral chemosensor (NBD-1) was prepared and applied to the recognition of the two enantiomers of the tetrabutylammonium salts of N-t-Boc-α-amino acids and chiral carboxylic acids including naproxen. In particular, the chiral recognition by the new fluorescent chiral chemosensor for the two enantiomers of N-t-Boc-threonine (tetrabutylammonium salt) was quite excellent, the Stern-Volmer constant ratio (K(D)/K(L)) for the two enantiomers being as high as 4.89.     

Sulfenylation of chiral Schiff bases

Summary The purpose of this study was to examine the conditions of sulfenylation reactions of chiral-amino esters Schiff bases to protect the chirality in the-position.     

酶法拆分手性化合物HPBE

R-HPBE(2-羟基4苯基丁酸乙酯)是一种重要的医药中间体,可以通过脂肪酶催化水解外消旋体得到。介绍了此催化过程的机理、工艺、产物检测等,并通过酶在疏水载体上的界面吸附对酶进行固定化,以提高酶活及对映选择性。