Showing papers on "Homochirality published in 2011"

The origin of biological homochirality

Abstract: The single handedness of biological molecules has fascinated scientists and laymen alike since Pasteur's first painstaking separation of the enantiomorphic crystals of a tartrate salt over 150 years ago. More recently, a number of theoretical and experimental investigations have helped to delineate models for how one enantiomer might have come to dominate over the other from what presumably was a racemic prebiotic world. Mechanisms for enantioenrichment that include either chemical or physical processes, or a combination of both, are discussed in the context of experimental studies in autocatalysis and in the phase behaviour of chiral molecules.

Chiral Amplification, Kinetic Pathways, and Morphogenesis of Helical Nanorods upon Self-assembly of Dipolar Merocyanine Dyes

Abstract: In this account we report on the self-assembly of bis(merocyanine) dyes into helical nanorods by emphasizing the kinetic pathways and the mechanistic aspects leading to chiral amplification. A complex self-assembly sequence of these dipolar dyes into well-defined helical nanorod structures has been revealed spectroscopically by time-dependent circular dichroism (CD) spectroscopy and microscopically by atomic force microscopy (AFM). This self-assembly sequence proceeds over several kinetically formed supramolecular intermediates, which are distinguished by their morphology and (chir)optical properties. Moreover, the kinetics for the formation of homochiral nanorods was studied, revealing that chiral amplification mechanisms can operate at different stages of self-assembly to afford energetically favored structures. The rates of these processes decrease strongly with decreasing chiral bias in the monomers or decreasing fraction of chiral co-monomers in mixtures of chiral and achiral monomers. For the fully equilibrated nanorods, however, strong chiral amplification directed by the “majority-rules” or “sergeants-and-soldiers” effect is observed.

Enantioselective CC Bond Formation as a Result of the Oriented Prochirality of an Achiral Aldehyde at the Single‐Crystal Face upon Treatment with a Dialkyl Zinc Vapor

Abstract: The origin of biological homochirality, such as that seen in l amino acids and d sugars, is one of the most important subjects for broad research.[1] Circularly polarized light,[2] chiral inorganic crystals,[3] such as quartz,[3c] chiral organic crystals,[4] and spontaneous absolute asymmetric synthesis[5] have been proposed as candidates for the origin of chirality. Supramolecular arrangement by an external chiral factor has also been suggested.[6] The induced chirality should be enhanced to high enantiomeric enrichment by suitable multiplication and amplification mechanisms,[7,8] such as amino acid catalyzed aldol reactions[9] and asymmetric autocatalysis.[10] Lahav,[4e] Holland and Richardson[11] originally suggested the concept of a reaction at the enantiotopic face of an achiral single crystal[11a] and later reported oxidation reactions of olefinic compounds.[11b] Because the reagents reacted directly with the oriented molecules in the crystal, the products formed in a stereospecific manner to provide optically active compounds corresponding to the prochirality of the substrate at the crystal surface. Since chiral compounds can be obtained from achiral compounds,[12] enantioselective reactions on a selected face have been considered as another possible origin of chirality. Recently, Kuhn and Fischer reported a reduction at the enantiotopic surface of a ketone to provide a chiral alcohol with up to 26 % ee.[13] Some chiral effects at enantiotopic surfaces have been reported, such as molecular recognition,[14a] crystallization,[14b] and dehydration.[14c] Thus, enantioselective C–C bond formation at specific enantiotopic surfaces is a challenge. We herein report the enantioselective addition of diisopropylzinc (iPr2Zn) at a particular single-crystal face of aldehyde 1 to form a chiral secondary alcohol 2 (Scheme 1). When a single-crystal surface was treated with iPr2Zn vapor, the enantioselective isopropylation proceeded to afford the chiral 5-pyrimidyl alkanol 2 with the absolute configuration corresponding to the oriented prochirality of the achiral aldehyde 1. Scheme 1 Enantioselective addition of diisopropylzinc to the pyrimidine-5-carbaldehyde 1 to form the 5-pyrimidyl alkanol 2. We previously reported that 2-(alkylethynyl)- and 2-(trialkylsilylethynyl)pyrimidine-5-carbaldehyde[15] serve as excellent substrates in asymmetric autocatalysis with the amplification of enantiomeric excess.[16] Thus, as an achiral substrate, we selected 2-(tert-butyldimethylsilylethynyl)pyrimidine-5-carbaldehyde (1), which can be prepared from 5-bromo-2-iodopyrimidine by a coupling reaction with tert-butyldimethylsilylacetylene and formylation (see the Supporting Information). A single crystal of 1 with well-defined crystal faces could be obtained by recrystallization from a solvent mixture of cumene and ethyl acetate by slow evaporation (Figure 1a). Single-crystal X-ray structure analysis demonstrated that aldehyde 1 belongs to the achiral space group , and the large parallelogram surfaces were determined to be enantiotopic (001) and () faces (Figure 1b).[17] These faces are colored sky blue and yellow in the unit-cell structure (Figure 1c). When aldehyde 1 was projected onto the yellow-colored face, the Si face of its formyl group was oriented toward the outside of the crystal; thus, the Re face was oriented toward the opposite blue-colored face. Figure 1 a) Structure of aldehyde 1 (space group: ). b) Microscopic image of the single crystal 1 and relative orientation of the prochiral aldehyde 1 at the (001) face. c) Unit cell of crystal 1. The yellow and blue planes correspond to enantiotopic surfaces. ... For the enantioface-selective addition of iPr2Zn, the single crystal, apart from the single reactive surface, was coated with an epoxy resin (Figure 2a), so that iPr2Zn vapor could access only one enantiotopic face. The enantiotopic (001) and () faces were defined on the basis of the parallelogram face shape and were independently exposed to iPr2Zn vapor without the use of a solvent for the reaction (Figure 2b). Dissolution would cause the disappearance of the molecular orientation of the achiral aldehyde in crystal 1. Figure 2 Enantioselective addition of diisopropylzinc to aldehyde 1 at an enantiotopic face of the single crystal 1. a) Apart from the single reactive (enantiotopic) surface, crystal 1 was coated with an epoxy resin. b) Enantiotopic parallelogram (001) and () ... When the enantiotopic (001) face was exposed to iPr2Zn for the addition reaction, alkanol (R)-2 (2.7 mg) was isolated with 46 % ee in 19 % yield based on the weight of the single crystal 1 (#1; Table 1, entry 1). The reaction at the morphologically determined (001) face afforded (R)-2 with 50–67 % ee and excellent reproducibility (Table 1, entries 2–4). On the other hand, when the () face was exposed to iPr2Zn, the opposite enantiomer (S)-2 was produced with 14–62 % ee (Table 1, entries 5–8). Table 1 Correlation between the exposed enantiotopic crystal face of aldehyde 1 and the absolute configuration of the alcohol product 2.[a] As the relationship between the absolute configuration of product 2 and the parallelogram face shape of reactant 1 was reproducibly constant, the orientation of prochiral aldehyde 1 in the crystal should correlate to the crystal morphology. Aldehyde 1 was not completely consumed in these solid–gas reactions; therefore, low chemical yields were observed. The wide variety of ee values should be due to the quality of the single crystal used as the reactant. To make sure of the stereochemical relationship, we conducted the exposure experiments by using opposite enantiotopic faces originating from one specific single crystal, which was cut into two pieces (Table 1, entries 9–16). In the reaction in entry 9 of Table 1, the (001) face of one half of the crystal (#9) was exposed to iPr2Zn vapor to afford (R)-2 with 55 % ee in 62 % yield. In contrast, reaction at the () face afforded (S)-2 with 48 % ee (Table 1, entry 10). The reproducibility of the formation of the major enantiomer was demonstrated clearly with single crystals #10–#12 (Table 1, entries 11–16). Alcohol 2 can also act as a highly efficient asymmetric autocatalyst in the homogeneous solution state.[10] Therefore, the obtained alcohol 2 was subjected to asymmetric autocatalysis with amplification of enantiomeric enrichment;[16b] this process afforded almost enantiomerically pure (R)- and (S)-2 with more than 99.5 % ee (Table 1, entries 17 and 18; see also Table S1 in the Supporting Information). We believe that the enantioselectivity observed in the present reaction is induced by the direct reaction of iPr2Zn vapor at a particular crystal face at which either the Si or the Re enantioface of the aldehyde is aligned with the outside of the crystal. By the use of one specific surface for the reaction, the direction of the nucleophile approach to the aldehyde 1 can be controlled. Therefore, chiral induction is possible through the choice of one enantiotopic face of an achiral single crystal 1. The formation of a racemate would be expected if the reaction occurred at both enantiotopic surfaces of a crystal, neither of which had been coated with a resin. In summary, we have demonstrated the enantioface-selective addition of iPr2Zn to pyrimidine-5-carbaldehyde 1. By selecting one enantiotopic crystal face, the chiral secondary alcohol 2 was formed with the absolute configuration corresponding to the two-dimensional chirality at the crystal surface. We could predict the absolute configuration of alcohol 2 from the parallelogram face shape. Furthermore, the ee value of product 2 could be enhanced to greater than 99.5 % by asymmetric autocatalysis with amplification of enantiomeric enrichment.

Controlling Chiral Organization of Molecular Rods on Au(111) by Molecular Design

Abstract: Chiral self-assembled structures formed from organic molecules adsorbed on surfaces have been the subject of intense investigation in the recent decade, owing both to relevance in applications such as enantiospecific heterogeneous catalysis or chiral separation as well as to fundamental interest, for example, in relation to the origin of biomolecular homochirality. A central target is rational design of molecular building blocks allowing transfer of chirality from the molecular to the supramolecular level. We previously studied the surface self-assembly of a class of linear compounds based on an oligo(phenylene ethynylene) backbone, which were shown to form a characteristic windmill adsorption pattern on the Au(111) surface. However, since these prochiral compounds were intrinsically achiral, domains with oppositely oriented windmill motifs and related conformational surface enantiomers were always realized in equal proportion. Here we report on the enantioselective, high yield chemical synthesis of a str...

Kinetics and Thermodynamics of Efficient Chiral Symmetry Breaking in Nearly Racemic Mixtures of Conglomerate Crystals

Abstract: The remarkable evolution of homochirality in Viedma-type conversions, which typically start from racemic or nearly racemic mixtures of d and l conglomerate crystals, is examined using dispersive kinetic models. One such model for nucleation rate-limited phase transformations is found to describe well the sigmoidal (“S”-shaped) conversion transients of those processes better than both the classical first-order (simple exponential) mechanism proposed in the current literature and the JMAEK (“Avrami”) equation traditionally used to model nucleation-and-growth processes. That finding is discussed in light of the secondary nucleation observed in similar, Kondepudi-type conversions as well as the recently proposed mechanisms of attrition-enhanced Ostwald ripening and solution phase racemization.

Homochiral Selectivity in RNA Synthesis: Montmorillonite-catalyzed Quaternary Reactions of D, L-Purine with D, L- Pyrimidine Nucleotides

Abstract: Selective adsorption of D, L-ImpA with D, L-ImpU on the platelets of montmorillonite demonstrates an important reaction pathway for the origin of homochirality in RNA synthesis. Our earlier studies have shown that the individual reactions of D, L-ImpA or D, L-ImpU on montmorillonite catalyst produced oligomers which were only partially inhibited by the incorporation of both D- and L-enantiomers. Homochirality in these reactions was largely due to the formation of cyclic dimers that cannot elongate. We investigated the quaternary reactions of D, L-ImpA with D, L-ImpU on montmorillonite. The chain length of these oligomers increased from 9-mer to 11-mer as observed by HPLC, with a concominant increase in the yield of linear dimers and higher oligomers in the reactions involving D, L-ImpA with D, L-ImpU as compared to the similar reactions carried out with D-enantiomers only. The formation of cyclic dimers of U was completely inhibited in the quaternary reactions. The yield of cyclic dimers of A was reduced from 60% to 10% within the dimer fraction. 12 linear dimers and 3 cyclic dimers were isolated and characterized from the quaternary reaction. The homochirality and regioselectivity of dimers were 64.1% and 71.7%, respectively. Their sequence selectivity was shown by the formation of purine-pyrimidine (54–59%) linkages, followed by purine-purine (29–32%) linkages and pyrimidine-pyrimidine (9–13%) linkages. Of the 16 trimers detected, 10 were homochiral with an overall homochirality of 73–76%. In view of the greater homochirality, sequence- and regio- selectivity, the quaternary reactions on montmorillonite demonstrate an unexpectedly favorable route for the prebiotic synthesis of homochiral RNA compared with the separate reactions of enantiomeric activated mononucleotides.

Molecular basis for chiral selection in RNA aminoacylation.

Abstract: The chiral-selective aminoacylation of an RNA minihelix is a potential progenitor to modern tRNA-based protein synthesis using l-amino acids. This article describes the molecular basis for this chiral selection. The extended double helical form of an RNA minihelix with a CCA triplet (acceptor of an amino acid), an aminoacyl phosphate donor nucleotide (mimic of aminoacyl-AMP), and a bridging nucleotide facilitates chiral-selective aminoacylation. Energetically, the reaction is characterized by a downhill reaction wherein an amino acid migrates from a high-energy acyl phosphate linkage to a lower-energy carboxyl ester linkage. The reaction occurs under the restriction that the nucleophilic attack of O, from 3′-OH in the terminal CCA, to C, from C=O in the acyl phosphate linkage, must occur at a Burgi-Dunitz angle, which is defined as the O–C=O angle of approximately 105°. The extended double helical form results in a steric hindrance at the side chain of the amino acid leading to chiral preference combined with cation coordinations in the amino acid and the phosphate oxygen. Such a system could have developed into the protein biosynthetic system with an exclusively chiral component (l-amino acids) via (proto) ribosomes.

Theoretical investigations into the enantiomeric and racemic forms of α-(trifluoromethyl)lactic acid

Abstract: There are many different hypotheses on the origin of biomolecular homochirality. One possible scenario concerns the enantiomeric enrichment of a nearly racemic solid via self-disproportionation of enantiomers. In particular, in a recent paper Soloshonok and co-workers showed a first example of optical self-purification of α-(trifluoromethyl)lactic acid by sublimation [V. A. Soloshonok et al., J. Am. Chem. Soc. 2007, 129, 12112]. Here we present detailed theoretical studies of α-(trifluoromethyl)lactic acid in the solid state as well as in the gas-phase dimeric form. The calculations of energy differences between dimers show that in the solid state the enantiomeric pure compound is energetically preferred, while in the gas phase the equilibrium shifts towards the racemic mixture although thermodynamic corrections cannot be neglected, thus providing a detailed microscopic explanation for the enantio-purification process for the first time.

One-pot synthesis of 5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) and spontaneous resolution upon crystallization

Abstract: 5-(8-ethoxycarbonyl-1-naphthyl)-10,15,20-triphenyl porphyrin (ENTPP) has been synthesized in a one-pot reaction, and the corresponding chiral crystalline samples have been obtained by spontaneous resolution. 1H NMR spectrum suggests it is mononaphthyl substituted species and an ethyl group is over the porphyrin plane. The structure has been further confirmed by X-ray crystallography. ENTPP·C6H14 (C57H50N4O2): monoclinic, P21, a = 10.707(2) A, b = 12.203(2) A, c = 17.858(4) A, β = 103.06(3)°, V = 2272.8(8) A3, Z = 2. The 8-position substituent, ester group, lies above the porphyrin plane and leads to the conformational chirality. The entire structure is built up with homochiral molecules, which leads to a chiral crystal through packing in P21 space group. Circular dichroism (CD) spectra have exhibited remarkable absorptions in the Soret band region, which further confirms the homochirality of the crystalline samples.

Asymmetric Autocatalysis. Automultiplication of Chiral Molecules

Abstract: Asymmetric autocatalysis (i.e. enantioselective autocatalysis) with amplification of enantiomeric excess is found in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde using pyrimidyl alkanol as an asymmetric autocatalyst. Pyrimidyl alkanol with extremely low enantiomeric excess automultiplies during three consecutive asymmetric autocatalyses with significant amplification of enantiomeric excess up to > 99.5 percent ee. The asymmetric outocotolysis has been applied to chiral discrimination of cryptochiral compounds. It also provides clues for clarifying the origin of homochirality. Circularly polarized light, inorganic chiral crystals, chiral crystals of achiral organic compounds and chiral compounds resulting from carbon isotope substitution act as chiral initiators in asymmetric autocatalysis affording highly enantioenriched products. Asymmetric autocatalysis in the reaction between pyrimidine-5-carboldehyde and diisopropylzinc has enormous power to amplify the statistically induced tiny enantiomeric imbalance (fluctuation of ee), thus, it is possible to form large amount of optically active compounds without the use of any chiral material. Spontaneous absolute asymmetric synthesis has been realized for the first time.

Origin of chiral selectivity in gas-phase serine tetramers

Abstract: Serine "magic-number" clusters have attracted substantial experimental and theoretical interest since their discovery. Serine undergoes marked chiral enrichment upon sublimation, which has been associated with the homochiral selectivity of the octamer. This process has been implicated in one possible mechanism leading to the origin of biological homochirality. While the octamer is the best known of the serine clusters, here we focus on the tetramer, the smallest serine cluster known to exhibit homochiral preference. This choice is based on its greater simplicity and tractability with accessible computational resources. Basin-hopping molecular dynamics simulations coupled to density functional theory calculations yield a "structural landscape" for low-lying configurations on the potential energy surface. The full range of enantiomeric compositions and charge states is investigated. Global energy minimum serine tetramers consist of a cage structure bonded by zwitterionic terminal groups. The participation of the serine hydroxyl side chains in hydrogen bonds with adjacent monomers drives the homochiral selectivity of serine tetramers. The configuration of the hydrogen bonding network is strongly dependent on enantiomeric composition and charge state. Smaller cations are incorporated into the center of the tetramer cage and effectively disable all side chain hydrogen bonding, while larger cations appear not to incorporate into the tetramer cage and are stabilized outside only in the homochiral case. The current theoretical data requires the introduction of a kinetic barrier to complete the model, limiting rearrangement from the basic cage configuration in some cases, which is discussed and probed directly by doubly-nudged elastic band transition state searches. These calculations elucidate a large barrier for reorganization of the cage, completing the theoretical understanding of the tetramers.

Two-dimensional chirality: Intelligent design

Abstract: Achiral molecules have now been assembled into a homochiral porous network at a solid–liquid interface. This has implications for practical processes such as separations, but also for understanding how homochirality — crucial in biological systems — arose from achiral or racemic species.

A "Quantum-Like" Approach to the Genetic Code

Abstract: A “quantum-like” analogy, introduced in 1998 by Rakocevic in his study of the bio-synthetic amino acid precursors, with the prime “quantum O37” in the background, is also considered in this paper as a guiding line of thought. We use and extend his results to derive (i) the multiplet structure of the standard genetic code, in a completely new and original way and (ii) several physicochemical quantities, as the number of nucleons in the 61 coded amino acids, the number of nucleons in 20, 23 and 61 amino acid biosynthetic precursors, the number of nucleons in 23 amino acids signals (AASs), the number of atoms in the 64 DNA-codons and in the 64 RNA-codons, and several other interesting quantities. In this way, we show that the fundamental set of seven fundamental amino acid precursors grouped into six amino acid families appears more informative than the larger set of twenty canonical amino acids. In a second part, we find once more a conspicuous numeric “manifestation” of serine, its protonated/neutral octamers and several other serine clusters; these clusters, in particular the serine octamer are thought to have been key players in the origin of homochirality. Also, we find, encoded, water (H2O), and, interestingly, the exact number of its characteristic water-water Hydrogen-Bond Contact/Non-Contact configurations (or “degeneracies”) according to the body-centered cubic (bcc) lattice gas model for water.

Active centrum hypothesis: The origin of chiral homogeneity and the RNA-world

Abstract: I propose a hypothesis on the origin of chiral homogeneity of bio-molecules based on chiral catalysis. The first chiral active centre may have formed on the surface of complexes comprising metal ions, amino acids, other coenzymes and oligomers (short RNAs). The complexes must have been dominated by short RNAs capable of self-reproduction with ligation. Most of the first complexes may have catalysed the production of nucleotides. A basic assumption is that such complexes can be assembled from their components almost freely, in a huge variety of combinations. This assumption implies that "a few" components can constitute "a huge" number of active centre types. Moreover, an experiment is proposed to test the performance of such complexes in vitro. If the complexes were built up freely from their elements, then Darwinian evolution would operate on the assembly mechanism of complexes. For the production of complexes, first their parts had to appear by forming a proper three-dimensional structure. Three possible re-building mechanisms of the proper geometric structure of complexes are proposed. First, the integration of RNA parts of complexes was assisted presumably by a pre-intron. Second, the binding of RNA parts of a complex may give rise to a "polluted" RNA world. Third, the pairing of short RNA parts and their geometric conformation may have been supported by a pre-genetic code. Finally, an evolutionary step-by-step scenario of the origin of homochirality and a "polluted" RNA world is also introduced based on the proposed combinatorial complex chemistry. Homochirality is evolved by Darwinian selection whenever the efficiency of the reflexive autocatalysis of a dynamical combinatorial library increases with the homochirality of the active centres of reactions cascades and the homochirality of the elements of the dynamical combinatorial library. Moreover, the potential importance of phospholipid membrane is also discussed.

Reactivity of Alanylalanine Diastereoisomers in Neutral and Acid Aqueous Solutions: a Versatile Stereoselectivity

Abstract: A good comprehension of the reactivity of peptides in aqueous solution is fundamental in prebiotic chemistry, namely for understanding their stability and behavior in primitive oceans. Relying on the stereoselectivity of the involved reactions, there is a huge interest in amino acid derivatives for explaining the spontaneous emergence of homochirality on primitive Earth. The corresponding kinetic and thermodynamic parameters are however still poorly known in the literature. We studied the reactivity of alanylalanine in acidic to neutral conditions as a model system. The hydrolysis into amino acids, the epimerization of the N-terminal residue, and the cyclization into diketopiperazine could be successfully identified and studied. This kinetic investigation highlighted interesting behaviors. Complex mechanisms were observed in very acidic conditions. The relative kinetic stability of the diastereoisomers of the dipeptide is highly dependent of the pH, with the possibility to dynamically destabilize the thermodynamically more stable diastereoisomers. The existence of the cyclization of dipeptides adds complexity to the system. On one hand it brings additional stereoselectivities; on the other hand fast racemization of heterochiral dipeptides is obtained.

Progress in studies on the RNA world.

Abstract: The montmorillonite-catalyzed reactions of D, L-ImpA with D, L-ImpU generates RNA-like oligomers. The structures of the dimers to pentamers were investigated and homochiral products were identified in greater amounts than would be expected if theoretical amounts of each were formed. The homochirality increased from 64% to 97% as the chain length increased from dimers to pentamers. Investigation of the effect of pH, occupancy of the interlayer space and the influence of various cations in the reaction provided further insight into physical process in the mechanism of the catalysis. A detailed analysis of dimers was carried out in view of there being key intermediates towards formation of higher oligomers. The study was extended to the synthesis of non-standard dimers including those formed with deoxy-ribonucleotides.

Parity-Violation Energy of Biomolecules—IV: Protein Secondary Structure

Abstract: The parity-violation energy difference between enantiomeric forms of the same amino acid sequence, from the amyloid β-peptide involved in Alzheimer’s desease, in both α-helix and β-sheet configurations, is investigated with ab-initio techniques. To this end, we develop an extension of the N2 computational scheme that selectively includes neighboring amino acids to preserve the relevant H-bonds. In agreement with previous speculations, it is found that the helical α structure is associated with larger parity-violation energy differences than the corresponding β form. Implications for the evolution of biological homochirality are discussed as well as the relative importance of various effects in determining the parity-violation energy.

Generation and Control of Chirality by Crystallization: Asymmetric Synthesis Using the Crystal Chirality in Fluid Media

Abstract: Many examples of solid-state photoreactions using chiral crystals composed of achiral materials and leading to optically active products have been successfully demonstrated and recognized as absolute asymmetric synthesis. Recently, we have discovered a new methodology for asymmetric synthesis using the molecular chirality in crystal as a source of homochirality in fluid media. The chirality can be effectively transferred to optically active products by asymmetric reactions involving nucleophilic reactions and an intermolecular photochemical reaction, and which had so far not been achieved in solid state reactions.

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

Abstract: We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.