Dynamic kinetic resolution of azlactones catalyzed by chiral Brønsted acids

Chiral Br?nsted acids have been shown for the first time to catalyze the dynamic kinetic resolution of azlactones. 3,3'-Bis-(9-anthryl)-BINOL phosphoric acid 3c is particularly effective in the case of 4-aryl-substituted substrates, producing 85-92% ee's.     

Enzymatic racemization of amines catalyzed by enantiocomplementary ω-transaminases

A strategy for the biocatalytic racemization of primary α-chiral amines was developed by employing a pair of stereocomplementary PLP-dependent ω-transaminases. The interconversion of amine enantiomers proceeded through reversible transamination by a prochiral ketone intermediate, either catalyzed by a pair of stereocomplementary ω-transaminases or by a single enzyme possessing low stereoselectivity. To tune the system, the type and concentration of a nonchiral amino acceptor proved to be crucial. Finally, racemization could be achieved by the cross-transamination of two different amines without a requirement for an external amino acceptor. Several synthetically and industrially important amines could be enzymatically racemized under mild reaction conditions.     

Efficient kinetic resolution of amino acids catalyzed by lipase AS ‘Amano’ via cleavage of an amide bond

Herein the efficient kinetic resolution of non-natural alpha-amino acids catalyzed by lipase AS ‘Amano’ via cleaving the amide bond is reported. The starting materials were the corresponding amino acid amides and the amino acids were generated with ees of up to 99% with E values of >600. These results indicated that the lipase AS ‘Amano’ could be a powerful amide hydrolase for the kinetic resolution of amino acid starting from the corresponding amino acid amides.     

Asymmetric Michael addition of substituted rhodanines to α,β-unsaturated ketones catalyzed by bulky primary amines

A bulky group was introduced by design into a diamine catalyst, and a series of robust and tunable bulky chiral primary amine catalysts were developed and successfully applied in the direct conjugate addition of substituted rhodanines to α,β-unsaturated ketones. High yields (up to 99%) and excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to 98% ee) were observed.     

Lipase-catalyzed kinetic resolution of α-hydroxymethylcycloalkanones with a quaternary carbon center. Chemoenzymatic synthesis of chiral pseudoiridolactones

The resolution of α-alkyl-α-hydroxymethylcyclopentanones 1 and cyclohexanones 3 has been efficiently achieved by using lipase-catalyzed transesterification reactions with vinyl acetate as the acylating agent. The enantiomeric selectivities were dependent on both the ring size of the cycloalkanone and the bulk of the carbon group located at the stereogenic quaternary center. The resolved α-alkyl-α-hydroxymethylcyclopentanones 1 were used as enantiopure (or enantioenriched) precursors for the synthesis of the optically active pseudoiridolactones 6–7.     

Synthesis of 4-aryl-substituted β-lactam enantiomers by enzyme-catalyzed kinetic resolution

Enantiopure 4-phenyl- and 4-(p-tolyl)-2-azetidinones 3a, 3b, 4a and 4b (with e.e.s of ≥96%) were prepared through lipase-catalyzed asymmetric butyrylation of the primary OH group of N-hydroxymethylated β-lactams (±)-5 and (±)-6 at the (R)-stereogenic centre or by lipase-catalyzed asymmetric debutyrylation of O-butyryloxymethyl-2-azetidinones (±)-7 and (±)-8 at the (R)-stereogenic centre. The ring-opening of lactams 5a, 5b, 6b and 8a with HCl/EtOH afforded the corresponding β-amino ester enantiomers 9a, 9b, 10a and 10b with e.e.s of ≥92%.     

Acylative kinetic resolution of racemic aromatic β-hydroxy esters catalyzed by chiral nucleophilic N-(1-arylethyl)benzoguanidines

An efficient acylative kinetic resolution of racemic aromatic β-hydroxy esters with cyclohexanecarboxylic anhydride was achieved using newly designed (R)-N-methylbenzoguanidine ((R)-NMBG) derivatives. A series of (R)-NMBG derivatives was synthesized by modifying the original (R)-NMBG catalyst with the introduction of branched N-substituents containing a stereogenic center, and their catalytic performance was evaluated. (R,R)-N-(1-(β-1-Naphthyl)ethyl)benzoguanidine [(R,R)-NβNpEtBG] was found to function as an efficient acyl transfer catalyst for the reaction of a broad variety of substrates, regardless of the substituent type and substitution pattern.     

Chemoenzymatic method for the preparation of γ-amino alcohols from phenylfuran-based aldehydes; lipase-catalyzed kinetic resolution of β-hydroxy nitriles

The chemoenzymatic preparation of novel enantiopure phenylfuran-based γ-amino alcohols with N-Boc-protection starting from the corresponding aldehydes is described. Enantiopurity (ee 98–99%) is introduced using Thermomyces lanuginosus lipase as the IMMTLL-T1-1500 preparation with β-hydroxy nitriles in an acylation/alcoholysis sequence in tert-butylmethyl ether.     

Chiral ruthenium-SDPs/diamine complexes-catalyzed enantioselective hydrogenation of α-alkyl arylacetones via dynamic kinetic resolution

The asymmetric hydrogenation of the conformationally flexible racemic α-substituted acyclic dialkyl ketones via dynamic kinetic resolution (DKR) has been developed by using Ru-SDPs/diamine catalysts. Chiral alcohols were produced in high yields with good to excellent enantioselectivities (85%–97% ee) and diastereoselectivities (up to 97:3). This hydrogenation reaction provided a new approach to the synthesis of the key intermediate of J-104118.     

Enantioselective synthesis of α-deuterium labelled chiral α-amino acids via dynamic kinetic resolution of racemic azlactones

Catalytic dynamic kinetic resolution (DKR) of racemic azlactones with EtOD using squaramide-based dimeric cinchona alkaloid organocatalysts is shown to be a highly effective strategy for the preparation of enantiomerically pure α-deuterated chiral α-amino acids.     

Asymmetric nucleophilic substitution of α-bromo amides via dynamic kinetic resolution for the preparation of dipeptide analogues

Asymmetric nucleophilic substitution reactions of α-bromo α-aryl acetamides derived from l-amino acids are described. The simple and practical syntheses of dipeptide analogues have been developed with dibenzylamine, TBAI and a base to provide 2a-2n and 4 in 50-98% yields with diastereomeric ratios from 74:26 to >99:1. Mechanistic investigations suggest that α-bromo acetamides are configurationally labile under the reaction condition and the primary pathway of the asymmetric induction is a dynamic kinetic resolution. The semiempirical calculations of two epimeric transition states of 1b found that (αS)-epimer is the faster reacting epimer with the formation of an intermolecular hydrogen bond that facilitates delivery of the amine nucleophile.     

Overexpression of Endogenous Xylose Reductase Enhanced Xylitol Productivity at 40 °C by Thermotolerant Yeast Kluyveromyces marxianus

Applied Biochemistry and Biotechnology - Xylitol is a valuable substance utilized by food and biochemical industries. NAD(P)H-dependent xylose reductase (XR)—encoded by the yeast KmXYL1...     

One-pot β-alkylation of secondary alcohols with primary alcohols catalyzed by ruthenacycles

A ruthenacycle-catalyzed one-pot β-alkylation of secondary alcohols with primary alcohols is described. A survey of four C–N chelate ruthenacycles synthesized via the cyclometallation reaction of phenylmethanamine, N-methylphenylmethanamine, N,N-dimethylphenylmethanamine, and naphthalen-1-ylmethanamine with [(η⁶-C₆H₆)RuCl₂]₂ was undertaken. All four complexes were found to be active with the phenylmethanamine-based ruthenacycle showing the best combination of reactivity and product selectivity among the four. An expanded scope of substrates was also studied with the inclusion of unsaturated primary alcohols. The reactivity trend observed gave insights into the role of hydrogen bonding in the catalytic mechanism involving transfer hydrogenation between the substrates and the transition metal catalyst.     

Asymmetric hydroazidation of α-substituted vinyl ketones catalyzed by chiral primary amine

We report herein the first example of asymmetric hydroazidation of α-substituted vinyl ketones by using chiral primary amines as the catalysts.A simple chiral primary-tertiary diamine catalyst derived from lphenylalanine was found to readily promote this aza-Michael addition reaction with enamine protonation as the key stereogenic step,thus enabling the effective synthesis of α-chiral β-azido ketones with good yields and moderate enantioselectivities.     

Synthesis of enantiomerically enriched α,α-disubstituted β,γ-epoxy esters using hydrolytic kinetic resolution catalyzed by salenCo(III)

Novel α,α-disubstituted epoxy esters were prepared in enantiopure form by hydrolytic kinetic resolution (HKR) of the corresponding racemic mixtures using chiral salenCo(III) as catalyst. The methodology provides a convenient route to enantioenriched β,γ-epoxy esters 2a, 2c and 2d.     

TEM study of band-like cellulose assemblies produced by Acetobacter xylinum at 4 °C

Two kinds of band-like cellulose assemblies, coarse and densestructures, are produced in Hestrin–Schramm medium at 4 °Cusing smooth colonies isolated from Acetobacter xylinumATCC23769, whereas ribbon cellulose assemblies are produced by the samecoloniesat 28 °C. The dense and the coarse band-like assembliesconsist of many strand-like cellulose entities (strands) and areextruded perpendicularly to the long axis of the bacterial cell. In an earlystage of incubation at 4 °C, the dense band-like assembly isproduced and the number of strands decreases gradually with increasingincubation time at 4 °C, probably because the number of activeTC subunits decreases as a result of the low-temperature shock for thebacteria.In contrast, the coarse band-like assembly is clearly observed after about 1h of incubation at 4 °C. The number of strands inthe coarse band-like assembly is about one third of that of the dense band-likeassembly and does not change during the incubation time of about 6h. In the selected-area electron diffraction (ED) experiment, thedense band-like assembly gives crystalline reflections corresponding to thecellulose II type crystal, while the coarse band-like assembly does not giveanycrystalline reflections under the same ED conditions.     

Self-association free bifunctional thiourea organocatalysts: synthesis of chiral α-amino acids via dynamic kinetic resolution of racemic azlactones

Concentration-independent high enantioselectivity in the dynamic kinetic resolution (DKR) of racemic azlactones affording chiral α-aminoesters has been achieved using self-association free thiourea-based dimeric cinchona alkaloid organocatalysts. Detailed experimental studies and single crystal X-ray analysis confirmed that these bifunctional organocatalysts I do not form H-bonded self-aggregates in either solution or solid state.