On the Prebiotic Synthesis of D‐Sugars Catalyzed by L‐Peptides: Assessments from First‐Principles Calculations

What accounts for a particular chiral selection in the case of a few sugars of prebiotic relevance, thereby mirroring the asymmetry observed in nature? By using first‐principles calculations, the generation of pentoses from glycolaldehyde (the initial product of the autocatalytic formose reaction), which has been detected in outer space), has been modeled by using L ‐Val‐L ‐Val as a primeval catalyst. Our theoretical study provides insight into the mechanism of this reaction and satisfactorily explains a few key molecular events. Our rationale agrees with the reported experimental data and shows that the D ‐configuration is only favored for ribose. L ‐pentoses are usually favored in the presence of L ‐configured dipeptides, as observed experimentally, although no chiral selection could be observed in the case of xylose. These results confirm that a prebiotic sugar soup could be fine‐tuned in the presence of shorter peptides as catalysts and that D ‐ribose would have also resulted in an advantageous imbalance for further amplification and chemical evolution.     

Enantioselectivity reversal by achiral additives in the Soai reaction: a kinetic understanding

Numerical kinetic simulations have been employed to understand the origin of enantioselectivity reversal of chiral beta-amino alcohol catalysts occurring in the presence of their achiral analogs in the autocatalytic addition of diisopropylzinc to pyrimidine carbaldehydes (Soai reaction). In a preceding work (Rivera Islas, J.; Lavabre, D.; Grevy, J. M.; HernAndez Lamoneda, R.; Rojas Cabrera, H.; Micheau, J. C.; Buhse, T. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13743-13748), we provided a possible explanation for the phenomenon of spontaneous mirror-symmetry breaking observed in this reaction. The effect of enantioselectivity reversal, giving rise to steep and abrupt transitions between opposed optically active states, has been identified by our current approach as another manifestation of such mirror-symmetry breaking capability. In the present case, we considered the involvement of the chiral catalyst and its achiral analog in the reaction network. Our modeling indicates that the enantioselectivity reversal can be either caused (i) by an interaction between the chiral and achiral additives or (ii) by an interaction of the customary products of the Soai reaction with the additives. The second option, which stands for the reversible inhibition of the chirally selective autocatalysts by the additives, could also explain a number of further additive effects in the Soai reaction reflecting the extraordinary sensitivity of this system toward the initial addition of almost any, even catalytically inactive, chiral substance.     

Stereoselective Aldol Reactions with α-Unsubstituted Chiral Enolates

The aldol reaction is among the most important methods of forming carbon-carbon bonds. The addition of an enolate to an aldehyde leads to the formation of at least one chiral center. In the case of α-substituted enolates it has to a large extent been possible to control the product stereochemistry, while the aldol reaction of α-unsubstituted chiral enolates was for many years a “problem child” for synthetic chemists because of its insufficient stereoselectivity. Progress in this area has only been made in the last few years using either new chiral auxiliaries or alternatives to the aldol reaction.     

Synthesis of new chiral aliphatic amino diselenides and their application as catalysts for the enantioselective addition of diethylzinc to aldehydes

[reaction: see text] A set of chiral aliphatic amino diselenides have been synthesized from readily available starting materials in a straightforward synthetic route via the ring-opening reaction of the parent aziridines. These ligands have been tested as catalysts for the enantioselective addition of diethylzinc to aldehydes. The influence of the alkyl group substituents on the stereoselectivity has been studied, and in the best case, an enantiomeric excess up to 99% could be obtained by using only 0.5 mol % of the chiral diselenide 3a.     

Synthesis of quaternary stereogenic centres via stereoselective intermolecular Friedel-Crafts reactions

Highly stereoselective Friedel-Crafts reactions have been performed using a chiral anthracene template to control the selectivity of the reaction. In the case of additions to fully substituted N-acyliminium ions, competitive elimination and condensation reactions were observed. Retro-Diels-Alder reaction of one of the reaction products led to a precursor that could be used for the construction of pyroglutamic acids bearing quaternary stereogenic centres.     

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.     

Formation of Chiral Structures in UV-Initiated Formose Reaction

It has been found that the UV-initiated formose reaction in an extremely concentrated aqueous solution of formaldehyde gives sugars and other biologically significant chiral compounds with sp³-hybridized carbon atom. The reaction leads to an optically active condensed phase, which is a result of the spontaneous spatial separation of enantiomers in the racemate into the antipodes, similarly to the separation of enantiomers of different chirality sign in the famous Pasteur experiments. In our opinion, such a scenario is as close as possible to the actually realized de novo scenario of synthesis of chiral prebiotic molecules and matrices.     

Toward the development of a general chiral auxiliary. Part 6: Structural effects on diastereoselection using camphor derived lactams: evaluation of (1R,4S)-1,7,7-trimethyl-3-azabicyclo[2.2.1]hept-5-en-3-one as a chiral controller

A new camphor-derived chiral lactam was designed, prepared and evaluated as a chiral controller in asymmetric Diels–Alder and aldol reactions. The new lactam, bearing a C(5)C(6) double bond, was anticipated to afford higher diastereofacial selection resulting from the removal of additional steric hindrance to reagent approach distal to the geminal dimethyl bridge by comparison with the previously studied saturated analogue (the favored mode approach in the saturated analogue). Surprisingly, a deterioration in the extent of diastereofacial selectivity was observed for both reaction types. These results are interpreted in terms of the geometric changes imposed upon the ring system as a whole by introduction of the unsaturation.     

Synthesis of hydantoins and dihydrouracils via thermally-promoted cyclization of ureidoacetamides

The synthesis of hydantoins and dihydrouracils from ureidoacetamides has been carried out at high temperature in glycol solvents. A series of substrates were prepared and examined to determine the effect of substrate structure, N-acyl substitution (X), and solvent on the course of the reaction. A dramatic effect was observed when using ureidoacetamides (e.g., X=N-methyl-N-phenyl), which led to higher yields, faster reaction times, and lower racemization of chiral substrates. The rate of racemization of a chiral hydantoin in the presence of dibenzylamine and N-methyl aniline has also been determined. The thermal cyclization methodology has been applied to the preparation of a complex hydantoin.     

Enantioselective oxidation of olefins catalyzed by chiral copper bis(oxazolinyl)pyridine complexes: a reassessment

Copper complexes of chiral tridentate pybox ligands synthesized using a modified procedure have been studied as catalysts for the enantioselective allylic oxidation of olefins. A variety of olefins have been used in this reaction. Using 5 mol% of a Cu(II) complex of the tridentate pybox ligand, phenylhydrazine, and tert-butyl perbenzoate as oxidant in acetone, optically active allylic benzoates were obtained up to 94% ee in few hours. It was also observed that the use of molecular sieves in the reaction did not alter the enantioselectivity. Temperature was found to be very crucial in rate of the enantioselective allylic oxidation of olefins. Using EPR spectra, it has been shown that the Cu(II) species is reduced to Cu(I) by phenylhydrazine and phenylhydrazone, but the reduction with the former is faster in comparison to the latter. It was concluded that the rate enhancement was not specific to the presence of phenylhydrazine or phenylhydrazone, but both were equally responsible provided acetone was used as a solvent.     

Chiral Imidazolium Prolinate Salts as Efficient Synzymatic Organocatalysts for the Asymmetric Aldol Reaction

Chiral imidazolium l-prolinate salts, providing a complex network of supramolecular interaction in a chiral environment, have been studied as synzymatic catalytic systems. They are demonstrated to be green and efficient chiral organocatalysts for direct asymmetric aldol reactions at room temperature. The corresponding aldol products were obtained with moderate to good enantioselectivities. The influence of the presence of chirality in both the imidazolium cation and the prolinate anion on the transfer of chirality from the organocatalyst to the aldol product has been studied. Moreover, interesting match/mismatch situations have been observed regarding configuration of chirality of the two components through the analysis of results for organocatalysts derived from both enantiomers of prolinate (R/S) and the trans/cis isomers for the chiral fragment of the cation. This is associated with differences in the corresponding reaction rates but also to the different tendencies for the formation of aggregates, as evidenced by nonlinear effects studies (NLE). Excellent activities, selectivities, and enantioselectivities could be achieved by an appropriate selection of the structural elements at the cation and anion.     

硅胶负载手性氨基醇聚合物的合成及其应用

以L-亮氨酸(L-Leu)为手性源,经酯化、格氏化、酰胺化等步骤制备手性单体(L-NALAA),以该单体为手性识别基团,在引发剂偶氮二异丁腈和交联剂乙二醇二甲基丙烯酸酯(EDMA)的作用下,与烯化功能硅胶发生自由基共聚反应,制备了新型键合硅胶手性固定相,其结构经FT-IR、TGA、EA表征。以4种对映异构体为模型药物对手性材料手性固定相的手性拆分性能进行研究,结果表明,手性材料手性固定相对奥美拉唑和兰索拉唑的拆分效果较好。     

Chiral binaphthylthiophosphoramide-cu(I)-catalyzed asymmetric addition of diethylzinc to N-sulfonylimines

In the presence of a catalytic amount of chiral binaphthylthiophosphoramide L2 (6 mol %) and Cu(I) (3 mol %), the asymmetric addition of diethylzinc to N-sulfonylimines could be achieved in good yields with moderate to high ee (63-93% ee) at 0 degrees C in toluene. A novel chiral binaphthylthiophosphoramide ligand system for this asymmetric addition reaction has been explored.     

Aziridine ring-opening reactions with chiral enolates. Stereocontrolled synthesis of 5-substituted-3-methyl-pyrrolidin-2-ones

A procedure for performing stereocontrolled aziridine ring-opening reactions with chiral enolates derived from (S,S)-(+)-pseudoephedrine amides has been developed leading to gamma-aminoamides in good yields. The diastereoselectivity of the reaction becomes controlled by the presence of the chiral auxiliary on the enolate, although the stereogenic center contained in the structure of the aziridine has a striking influence on the stereochemical course of the reaction which results in the presence of the corresponding matched and mismatched combinations. Besides, the sense of the asymmetric induction of the chiral auxiliary has resulted to be the opposite to the one found with other type of electrophiles, although it is in good agreement with the trend observed in the reaction of the same kind of enolates with epoxides. Finally, the obtained gamma-aminoamide adducts were converted into enantiopure gamma-amino acids, gamma-aminoesters, and pyrrolidin-2-ones using easy to perform and high yielding reactions.     

Preparation and Reactions of Amino Acid Ester Sulfones as New Remote Asymmetrical Induced Reagents

The development of chiral auxiliary-controlled asymmetric synthesis has been receiving increasing interest in recent yearsfi,2] Various chiral auxiliary reagents have been observed[3] and a lot of results showed that variation of the chiral auxiliary could influence asymmetric induction. Recently, it has been reported the reaction of the aminated sulfones as a remote chiral auxiliary with α,β-unsaturated carbonyl compounds.[4] Here we would like to report the preparation of amino acid ester sulfones as new remote asymmetrical induced reagents and their reactions with α,β-unsaturated esters.     

Kinetic and thermodynamic preferences for the diastereoselective oxidative addition of H(2) to trans-Ir(PR(3))(2)(CO)Cl: monodentate chiral phosphines may impart exceptional degrees of diastereoselectivity

Studies on square planar iridium complexes of the type trans-Ir(PR(3))(2)(CO)Cl, where PR(3) is PhP[(C(5)Me(4))](2), PhP[Me(2)C(4)H(6)], or PhP[Pr(i)(2)C(4)H(6)], demonstrate that monodentate chiral phosphines impart exceptional degrees of diastereoselectivity in the oxidative addition of H(2). Thus, the oxidative addition of H(2) to the two faces of the meso isomer (R,S)-trans-Ir(PR(3))(2)(CO)Cl proceeds with a kinetic diastereoselectivity which exceeds that for related square planar iridium complexes employing bidentate chiral phosphine ligands. Furthermore, the kinetically favored dihydride is not favored thermodynamically, and the magnitude of the inversion of the kinetic and thermodynamic selectivities is greater than has previously been observed using bidentate phosphines.     

Stochastic interpretation of the asymmetry of enantiomeric distribution observed in the absolute asymmetric Soai reaction

The asymmetry of the experimentally observed distribution of enantiomeric excesses in the Soai reaction [Kawasaki, T.; Suzuki, K.; Shimizu, M.; Ishikawa, K.; Soai, K. Chirality 2006, 18, 479–482] is interpreted in this work using the continuous time discrete state stochastic kinetic approach assuming the presence of minor amounts of a chiral initiator at the beginning of the reaction. Schemes with first order and second order enantioselective autocatalysis are considered with the latter giving a better interpretation of the published results. For the number of initiator molecules, Poisson and geometric distributions are considered and give equally good fits. It is shown that the macroscopically observed asymmetry of the distribution of enantiomeric excesses could be the consequence of a few molecules acting as asymmetric inductors.     

Aqueous ethanol: a suitable medium for the diastereoselective Diels–Alder reaction mediated by chiral bases

Abstract

The effect of aqueous ethanol medium on the outcome of a Diels–Alder (DA) reaction with regard to yields, reaction time, and the stereoselectivity observed has been studied. When the reaction between anthrone and (R)-(+)-N-α-methylbenzylmaleimide was carried out in aqueous ethanol in presence of achiral base no diastereoselectivity could be obtained. Moderate diastereoselectivity could be achieved in presence of chiral bases. Use of biodegradable aqueous ethanol solvent for the reaction and stereoselective nature of the reactions studied provide a greener approach.     

Gamma-radiolysis of chiral molecules: R(+)-limonene, S(-)-limonene and R(-)-a-phellandrene

Three isomeric chiral terpenes, R(+)-limonene, S(-)-limonene and R(-)-a-phellandrene were γ-radiolyzed in sealed vials at room temperature with a total radiation dose of 317 kGy. The radiolyzed samples were analyzed by FT-IR, electronic absorption spectroscopy, liquid chromatography using a diode-array detector (HPLC-DAD) and by polarimetry. Despite a relatively high radiation dose used, all the chiral molecules selected have shown a low radioracemization rate. This fact and the role played by the impurities in the selective radio-degradation of one of the two enantiomers has been discussed in the context of the origin of chirality in prebiotic molecules and the chirality enhancement in a prebiotic world. The results were also discussed in the frame of the radiosterilization technique of chiral drugs, perfumes and food components. This revised version was published online in July 2006 with corrections to the Cover Date.     

Catalytic Asymmetric Diels–Alder Reaction of Quinone Imine Ketals: A Site‐Divergent Approach

The catalytic asymmetric Diels–Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl‐substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels–Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3‐alkyl quinone imine ketals from the inherently favored unsubstituted C?C bond to the disfavored alkyl‐substituted C?C bond.