Károly Micskei

Oscillatory symmetry breaking in the Soai reaction

A kinetic model of spontaneous amplification of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes is extended by a negative feedback process. Simulations based on the extended model result in large-amplitude oscillations both in a continuous-flow stirred tank reactor (CSTR) and in a semibatch configuration under optimized initial conditions. When sustained oscillations are maintained in a CSTR, no enantiomeric product distribution could be observed in the calculated series; the system keeps its initial enantiomeric ratio endlessly. During damped oscillations, or steady-state conditions, however, chiral amplification from a very small initial enantiomeric excess to more than 99% occurs in a semibatch configuration. Calculations indicated spontaneous enantiomeric product enrichment (i.e., accumulation of one of the enantiomers at the cost of the other one) from strictly achiral starting conditions in a semibatch configuration due to the inherent numerical error of the integrator method, which can be regarded as a model of the statistical fluctuation in the numbers of enantiomeric molecules.

Isotope Chirality and Asymmetric Autocatalysis: A Possible Entry to Biological Chirality

Natural-abundance isotopic substitution in isotopically prochiral groups of otherwise achiral molecules can provide stochastically formed enantiomeric excesses which exceed the sensitivity threshold of sensitive asymmetric autocatalytic (Soai-type) reactions. This kind of induction of chirality should be taken into consideration in in vitro model experiments and offer a new kind of entry into primary prebiotic or early biotic enantioselection in the earliest stages of molecular evolution.

Amino acid ligand chirality for enantioselective syntheses

Amino acids are attractive sources of chirality in stoichiometric or catalytic transition metal/organic chemistry. In spite of easy availability and other advantages, the application of these ligands is hindered by several problems. Now, at the dawn of emerging d‐amino acid biochemistry, efforts in this direction are becoming increasingly important. The results of research on application of amino acid ligands for transition‐metal reagents in organic syntheses are reviewed in the present work.

Asymmetric induction by amino acid ligands in chromium(II)-assisted reduction of ketones

Abstract Asymmetric reduction of acetophenone by Cr(II)/amino acid/water/DMF system is reported. Chemical yields up to 94%, enantiomeric excesses up to 74% were observed. The relevance to the Nozaki–Hiyama–Kishi reaction is discussed.

Long-live glycosyl-chromium(III) complex intermediates in aqueous medium. Preparation of pyranoid glycals

Abstract Acetylated glycosyl-chromium(III)L (L=EDTA, NTA, IDA) complex intermediates ( 1 ) were detected in aqueous medium, with half-life times of 30–300 minutes. The decay of these intermediates led to glycals ( 7–9 ) of high purity in preparatively usable 70–90% yields.

First molecules, biological chirality, origin(s) of life

Origin(s) of biological chirality appear(s) to be intimately connected to origin(s) of life. Prebiotic evolution toward these important turning points can be traced back to single chiral molecules. These can be small (monomeric) units as amino acids or monosaccharides or oligomers as oligo-RNA type molecules. Earlier speculations about these two kinds of entries to biological chirality are critically reviewed.

Enantioselective reduction of prochiral ketones by chromium(II) complexes with amino acid ligands as the source of chirality

Abstract Prochiral ketones were reduced to enantiomerically enriched secondary alcohols by Cr(II)[L-amino acid] complexes in good yields and moderate enantioselectivity.

Preparation of acylated pyranoid glycals in neutral aqueous medium by using chromium(II) complexes as reagents

Abstract Reactions of 2,3,4,6- tetra -O- acetyl -α- d -glucopyranosyl bromide (3) with chromium(II)L complexes (L = EDTA, NTA, IDA, GLY, MAL) in neutral (5 3,4,6- tri -O- acetyl-1,5-anhydro-2-deoxy- d -arabino- hex-1-enitol (13) in 70–90% yields and >95% purity. Complexes of Cr(II) with L = EDTA, NTA were similarly efficient with 2,3,4,6- tetra -O- acetyl -α- d -glucopyranosyl chloride (2) in furnishing glucal 13, while with L = IDA, GLY, MAL hydrolysis of 2 could not be suppressed. Under the same conditions [CrII(EDTA)]2− also efficiently gave the corresponding glycals 14–19 from 2,3,4,6- tetra -O- benzoyl - ( 4 ) and 2,3,4,6- tetra -O- pivaloyl -α- d -glucopyranosyl bromide (5), per-O-acetylated α- d -galactopyranosyl chloride (6) and bromide (7), α- d -mannopyranosyl chloride (8), α- d -xylopyranosyl chloride (9), and bromide (10), β- d -arabinopyranosyl bromide (11), and α- l -rhamnopyranosyl chloride (12).

Asymmetric synthesis of amino acids by Cr(II) complexes of natural amino acids

Abstract Stoichiometric reduction of the C,N double bond of oxime precursors of α-amino acids was performed in aqueous media by Cr(II) complexes of natural amino acids. The reduction of oximes of α-ketophenylacetic, α-keto-β-phenylpropionic and α-ketopropionic acids proceeded up to >90% conversion and 2–30% enantiomeric excess. 1:2 complexes of Cr(II) with l -alanine, l -valine, l -aspartic acid, l -histidine and l -phenylalanine were used as reducing agents. The reduction of α-(oximino)phenylacetic acid showed increasing e.e. (and decreasing conversion) with increasing temperature.

Preparation of acetylated pyranoid glycals from glycosyl halides by chromium(II) complexes under aqueous biphasic conditions

Reactions of chromium(II) aminocarboxylate complexes (ethylenediamine-tetraacetate, nitrilo-triacetate, imino-diacetate) with acetylated glycopyranosyl chlorides or bromides in liquid-liquid or solid-liquid biphasic media (such as water-diethylether, water-ethyl acetate or halosugar-water) give the corresponding glycals in 75-97% yield.