CSTR和批式反应器中酶法拆分萘普生的比较

比较了批式反应器和连续流动搅拌反应器中酶动力学拆分萘普生的不同之处。从宏观反应器平衡角度,推导出了在ＣＳＴＲ中不同于在批式反应器中的酶立体选择性,产物对映体过量值和反应转化率的定量关系式,并通过脂肪酶催化的萘一甲酯的不对称水解反应得到了证实。     

高碘酸盐-硫脲-硫酸反应体系的非线性动力学

研究了KIO4-SC(NH2)2-H2SO4反应体系在封闭、半封闭以及开放系统中的非线性动力学行为.发现在封闭体系中体系的吸光度、铂电极电位和pH值呈现单峰或准振荡现象;在半封闭和开放系统中体系的铂电极电位和碘电极电位均呈振荡现象.封闭、半封闭及开放系统的动力学曲线受体系酸度和初始浓度比值犤KIO4犦0/犤SC(NH2)2犦0的影响.对照其在封闭、半封闭和开放系统中的动力学行为,以碘单质产生和消耗驱使的反应动力学可解释该反应体系的复杂现象.     

高碘酸盐-硫脲-硫酸反应体系的非线性动力学

研究了KIO4 SC(NH2)2 H2SO4反应体系在封闭、半封闭以及开放系统中的非线性动力学行为.发现在封闭体系中体系的吸光度、铂电极电位和pH值呈现单峰或准振荡现象；在半封闭和开放系统中体系的铂电极电位和碘电极电位均呈振荡现象.封闭、半封闭及开放系统的动力学曲线受体系酸度和初始浓度比值[KIO4]0/[SC(NH2)2]0的影响.对照其在封闭、半封闭和开放系统中的动力学行为,以碘单质产生和消耗驱使的反应动力学可解释该反应体系的复杂现象.     

2D Ising Model for Adsorption-induced Enantiopurification of Racemates

Mechanisms for the spontaneous transformation of achiral chemical systems into states of enantiomeric purity have important ramifications in modern pharmacology and potential relevance to the origins of homochirality in life on Earth. Such mechanisms for enantiopurification are needed for production of chiral pharmaceuticals and other bioactive compounds. Previously proposed chemical mechanisms leading from achiral systems to near homochirality are initiated by a symmetry-breaking step resulting in a minor excess of one enantiomer via statistical fluctuations in enantiomer concentrations. Subsequent irreversible processes then amplify the majority enantiomer concentration while simultaneously suppressing minority enantiomer production. Herein, equilibrium adsorption of amino acid enantiomer mixtures onto chiral and achiral surfaces reveals amplification of surface enantiomeric excess relative to the gas phase; i. e. enantiopurification of chiral adsorbates by adsorption. This adsorption-induced amplification of enantiomeric excess is shown to be well-describe by the 2D Ising model. More importantly, the 2D-Ising model predicts formation of homochiral monolayers from adsorption of racemic mixtures or prochiral molecules on achiral surfaces; i. e. enantiopurification with no apparent chiral driving force.     

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine-5-carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high-resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively.     

Three-dimensional description of the spontaneous onset of homochirality on the surface of a conglomerate crystal phase

The spontaneous emergence of homochirality in an initially racemic system can be obtained in far-from-equilibrium states. Traditional models do not take into account the influence of inhomogeneities, while they may be of great importance. What would happen when one configuration emerges at one position, and the opposite one at another position? We present a discrete three-dimensional model of conglomerate crystallization, based on 1,1'-binaphthyl crystallization experiments, that takes into account the position and environment of every single elementary growth subunit. Stochastic simulations were performed to predict the evolution of the crystallization process. It is shown that the traditional view of the symmetry breaking can then be extended. Fluctuations of the fixed points related to inhomogeneities are observed, and complex behavior, such as local instabilities, transient structures, and chaotic behavior, can emerge. Our modeling indicates that such complex phenomena could cause large fluctuation of the final enantiomeric excess that is observed experimentally in binaphthyl crystallization. The results presented in this article show the importance of inhomogeneities in understanding enantiomeric excess generated in crystallization and the inadequacy of the models based on the assumption of homogeneity.     

高碘酸盐-亚硫酸盐反应体系的复杂动力学

研究了KIO4-Na2SO3-H2SO4 反应体系的复杂动力学，在酸性条件下（pH<3），发现碘电位、Pt电极电位和pH在封闭体系中显示单峰振荡以及半封闭体系和开放体系中的振荡现象.振荡现象受[Na2SO3]0/[KIO4]0比值以及体系的酸度影响.实验结果表明该体系可能为I2生成和I2消耗所驱动的振荡反应；所拟的反应机理解释了体系所显示的复杂动力学现象.     

Chiral symmetry breaking in a microscopic model with asymmetric autocatalysis and inhibition

Asymmetric autocatalysis and inhibition have been proposed as key processes in the spontaneous emergence of chiral symmetry breaking in a prebiotic world. An elementary lattice model is formulated to simulate the kinetics of chiral symmetry breaking via autocatalysis and inhibition in a mixture of prochiral reactants, chiral products, and inert solvent. Starting from a chirally unbiased initial state, spontaneous symmetry breaking occurs in spite of equal a priori probability for creating either product enantiomer, and the coupled reaction-diffusion processes subsequently amplify the random early-stage symmetry breaking. The processes of reaction and diffusion are kinetically intertwined in a way leading to competition in the appearance of enantiomeric excess. An effective transition temperature can be identified below which spontaneous symmetry breaking appears. In the absence of inhibition, reactions are predominantly autocatalytic under both reaction control (fast diffusion, slow reaction) or diffusion control (fast reaction, slow diffusion) conditions. In the presence of inhibition, simulations with different system sizes converge to the same transition temperature under reaction control conditions, and in this limit the reactions are predominantly nonautocatalytic.     

Synthesis of chiral 1,3-diamines derived from cis-2-benzamidocyclohexanecarboxylic acid and their application in the Cu-catalyzed enantioselective Henry reaction

In this study, 13 different chiral 1,3-diamines were synthesized from (-)-cis-2-benzamidocyclohexanecarboxylic acid. They were successfully applied as ligands in the Cu-catalyzed asymmetric Henry reaction between benzaldehyde and nitromethane. It was confirmed that the enantioselectivity of the product could be controlled by the substituents on the two amino groups. A time-course study revealed a decrease in product enantioselectivity caused by spontaneous retro-Henry reaction, which was suppressed by conducting the reaction at 0 °C. This versatile reaction afforded various β-nitroalcohols in excellent yields and enantioselectivities (up to 98% yield, 91% enantiomeric excess) under the optimized reaction conditions. The chiral induction mechanism was explained on the basis of a previously proposed transition-state model.     

Enantioenrichment in sublimed amino acid mixtures

A real amplification of an initial enantiomeric excess can be detected when two amino acids are sublimed at high temperature, even if one of the components is a racemic compound that does not convert into a conglomerate by sublimation.     

Systematic Studies using 2‐(1‐Adamantylethynyl)pyrimidine‐5‐carbaldehyde as a Starting Material in Soai’s Asymmetric Autocatalysis

Herein, we present a new substrate for the Soai reaction, which has an adamantylethynyl residue ( 1 g ) and exhibits asymmetric autocatalysis, yielding products with enantiomeric excesses above 99 %. For the first time, all reactions were performed on a parallel synthesizer system to ensure identical reaction conditions. A detailed systematic study of reaction parameters was performed and we report the highest enhancements of enantiomeric excess reported so far in the Soai reaction in one reaction cycle (7.2→94.1 % ee or 3.1→92.1 % ee). Our results led to a set of reaction parameters that yield reproducible results. Therefore, our new starting material 1 g is suitable for systematic and mechanistic studies on this remarkable reaction. A series of experiments designed to quantify the amplification of enantiomeric excess demonstrated that the reaction can be used in principle as a tool for the detection of low enantiomeric excesses: under definite conditions, an unknown low enantiomeric excess (0.1–7 %) was amplified to a detectable one. A back calculation to the original value offers a new method for the determination of small enantiomeric excesses.     

Asymmetric amplification by kinetic resolution using a racemic reagent: example in amine acetylation

The reaction of a racemic reagent on a mixture of enantiomers with small ee (ee=enantiomeric excess) has been studied for amine acylation. A substantial asymmetric amplification could be realized, for example, from 67 to >95.5 ee. The combination of asymmetric amplifications is subsequently discussed. Two sequential asymmetric amplifications, one using a racemic reagent and another using a positive nonlinear effect allowed us to start from 1.5 % ee and end with a large amount of a product of 97 % ee.     

Catalytic asymmetric synthesis of β-triazolyl amino alcohols by asymmetric transfer hydrogenation of α-triazolyl amino alkanones

The synthesis of optically active β-triazolyl amino alcohols was carried out via ruthenium catalyzed asymmetric transfer hydrogenation of α-triazolyl amino alkanones. This reaction proceeds under mild reaction conditions with up to 99% yield and 99.9% enantiomeric excess (ee). This protocol was applied to the synthesis of an enantiopure antitubercular agent and its arylated product with retention in enantiomeric purity. The absolute configuration at the stereogenic center of the chiral product as found to be (S).     

Bioscillation and Birhythmicity in the H_2O_2-KSCN-CuSO_4-NaOH System

Two kinds of different mechanistic oscillations can be displayed in the H_2O_2-KSCN-CuSO_4-NaOH system. One discovered by this study is the pH oscillation in a continuous flow stirred tank reactor(CSTR) resulting from the oxidation of KSCN. The other is the oscillation of H_2O_2 decomposition in both CSTR and batch reactors(reported by Orbáin in 1986). Under appropriate experimental conditions, the system exhibits a birhythmicity in a CSTR. Two different pH oscillations are reported here. The pH oscillations which accompany the decomposition of H_2O_2 exist in the batch reactor and the CSTR at a high flowrate, but the pH oscillations in a CSTR at a low flowrate originates from proton positive and negative feedback in the oxidation of KSCN. The oscillation of non-catalyzed oxidation of KSCN by hydrogen peroxide in a CSTR can be found. Also we have observed whether Cu~(2+) exists or not in the batch system, the pH increases to near neutral ultimately after pH drops twice.     

Chiral schiff bases synthesized from terpenes of pinane series in asymmetric metall complex oxidation of sulfides

The absolute configuration of α-hydroxyaldehyde obtained from verbenol epoxide in the presence of clay was determined. Two new Schiff bases were synthesized from the aldehyde obtained. The compounds can be used as ligands in the asymmetric vanadium-catalyzed oxidation of sulfides to sulfoxides. The structure of initial sulfides significantly affects the value of the enantiomeric excess in the obtained sulfoxides: the highest enantiomeric excess is observed in the oxidation of thioanisole.     

Amplification of chirality as a pathway to biological homochirality

Amplification of enantiomeric enrichment is a key feature for the chemical evolution of biological homochirality from the origin of chirality. The aggregations of the enantiomers by diastereomeric interactions enable the modification of their enantiomeric excess during some chemical processes. Fluorine-containing chiral compounds possess large amplification effect via distillation, sublimation and achiral chromatography by self-disproportionation. Asymmetric amplifications in enantioselective catalysis occur by the differential formation and reactivity between homochiral and heterochiral aggregate in solution.We described the amplification of ee in asymmetric autocatalysis of 5-pyrimidyl alkanol in the reaction between diisopropylzinc and pyrimidine-5-carbaldehdye. During the reactions extremely low ee (ca. 0.00005% ee) can be amplified to achieve more than 99.5% ee. Since the proposed origins of chirality such as CPL, quartz, chiral organic crystals of achiral compounds and statistical fluctuation of ee can initiate the asymmetric autocatalysis with amplification of ee, the proposed origin of chirality can be linked with enantiopure organic compound in conjunction with amplification of ee by asymmetric autocatalysis. In addition, we described that the carbon isotopically chiral compound triggers the asymmetric autocatalysis of 5-pyrimiodyl alkanol to afford the enantioenriched product with the absolute configuration correlated with that of carbon isotope chirality, that is, isotope chirality including hydrogen isotopes can control the enantioselectivity of asymmetric addition of alkyl metal reagent to aldehyde.     

Enantiomeric recognition and interactions

The consequences in a chemical reaction of the non-bonding interactions between molecules of one configuration on the one hand, and molecules of opposite configuration on the other hand are discussed. The reaction rates and product ratios in the reaction of a chiral compound depend upon the enantiomeric excess of the substrate. An antipodal interaction effect is observed in a phenol coupling reaction, a reductive camphor dimerization and a camphor reduction.     

Amplification of enantiomeric excess, mirror-image symmetry breaking and kinetic proofreading in Soai reaction models with different oligomeric orders

A comprehensive kinetic analysis of three prototypical autocatalytic cycle models based on the absolute asymmetric Soai reaction is presented. The three models, which can give rise to amplification of enantiomeric excess and mirror-image symmetry breaking, vary by their monomeric, dimeric or trimeric order of the assumed catalytic species. Our numerical approach considered the entire chiral combinatorics of the diastereomeric interactions in the models as well as the multiplicity of coupled reversible reactions without applying fast equilibration or quasi-steady state approximations. For the simplest monomeric model, an extensive range of parameters was explored employing a random grid parameter scanning method that revealed the influence of the parameter values on the product distribution, the reaction-time, the attenuation or amplification of enantiomeric excess as well as on the presence or absence of mirror-image symmetry breaking. A symmetry breaking test was imposed on the three models showing that an increase in the catalytic oligomer size from one to three leads to a higher tolerance to poorer chiral recognition between the diastereoisomers and identifies the greater impact of the diastereoisomeric energy difference over an imperfect stereoselectivity in the catalytic step. This robustness is understood as a particular case of so-called kinetic proofreading in asymmetric autocatalysis.     

Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunction with asymmetric autocatalysis

Enantiomerically enriched pyrimidyl alkanol with either S or R configuration was obtained stochastically from the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc without adding chiral substances in conjunction with subsequent asymmetric autocatalysis, leading to amplification of the enantiomeric excess.     

Racemic D,L-asparagine causes enantiomeric excess of other coexisting racemic D,L-amino acids during recrystallization: a hypothesis accounting for the origin of L-amino acids in the biosphere

When recrystallizations were performed using a mixture of 12 D,L-amino acids (alanine, aspartic acid, arginine, glutamic acid, glutamine, histidine, leucine, methionine, serine, valine, phenylalanine, and tyrosine) with excess D,L-asparagine, all amino acids with the same configuration as asparagine were preferentially co-crystallized, indicating that it is the nature of a mixture of racemic amino acids to produce a spontaneous high enantiomeric excess.