Assessment of C-type halohydrin dehalogenase stability

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Diastereoselective Aldol Reaction of 7-Bromo-5-pyrido-1,4-benzodiazepin-2-one; Relative and Absolute Configuration of All Stereoisomers

Aldol reaction of C(3) carbanion of 7-bromo-5-pyrido-1,4-benzodia-zepin-2-one (1) with representative aliphatic and aromatic aldehydes and ketones afforded racemic mixtures syn/anti-7-bromo-3-(1\u27-hydroxy-1\u27-phenylmethyl)-1-methyl-5-(2\u27-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (2/3), syn/anti-7-bromo-3-(1\u27-hydroxy-1\u27-phenylethyl)-1-methyl-5-(2\u27-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin -2-one (4/5) and syn/anti-7-bromo-3-(1\u27-hydroxy-2\u27-methylpropyl)-1-methyl-5-(2\u27-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (6/7) with 60-85% diastereoselectivity. For prevailing diastereomeric racemates (±)-2 and (±)-4, syn relative configuration is deduced, whereas the prevailing diastereomer (±)-7 has anti configuration. Configurational assignment is based on NMR data and X-ray structure analysis, and the origin of inversion of diastereoselectivity is discussed. Racemic mixtures were separated on chiral HPLC column, and on the basis of the CD spectra (3R) absolute configuration was determined for (+)-enantiomers, and (SS) configuration for (-)-enantiomers. Consequently, (3R,1\u27S) configuration is assigned to syn-(+)-enantiomers and (3R,1\u27R)-configuration to anti-(+)-enantiomers. In an attempt to use enantiomerically pure compounds 2-7 as catalysts in asymmetric alkylation of benzaldehyde by diethylzinc, these ligands proved chemically and configuration-ally unstable

Biodegradation of 1,2,3-Trichloropropane to Valuable (S)-2,3-DCP Using a One-Pot Reaction System

1, 2, 3-trichloropropane (TCP) being one of the important environmental pollutants, has drawn significant concern due to its highly toxic and carcinogenic effects. In this study, we built a one-pot reaction system in which immobilized haloalkane dehalogenase (DhaA31) and halohydrin dehalognase (HheC) were used to catalyze the recalcitrant TCP to produce 2, 3-dichloro-1-propanol (2, 3-DCP) by removing epichlorohydrin (ECH). SinceHheCdisplays a highRenantiopreference toward 2, 3-DCP, the production of enantiopure (S)-2, 3-DCP was expected. However, the enantioselective resolution of (R, S)-2, 3-DCP by HheC was greatly inhibited by the circular reaction occurring between the product ECH and 1, 3-dichloro-2-propanol (1.3-DCP). To resolve this problem, HZD-9 resin-based in situ product removal was implemented. Under the optimized conditions, TCP was completely consumed, resulting in optically pure (S)-2, 3-DCP with enantiomer excess (e.e) > 99% and 40% yield (out of the 44% theoretical maximum). The scale-up resin-integrated reaction system was successfully carried out in 0.5 L batch reactor. Moreover, the system could be reused for 6 rounds with 64% of original activity retained, showing that it could be applied in the treatment of large volumes of liquid waste and producing enantiopure (S)-2, 3-DCP

Sequential Kinetic Resolution Catalyzed by Halohydrin Dehalogenase

A sequential kinetic resolution catalyzed by halohydrin dehalogenase was employed for the synthesis of two valuable enantiopure building blocks. Resolution of methyl 4-chloro-3-hydroxybutanoate methylester ((R,S)-2) with use of a Trp249Phe mutant of halohydrin dehalogenase yielded methyl 4-cyano-3-hydroxybutanoate methylester ((S)-4) with 96.8% ee (40% yield) and (S)-2 with 95.2% ee (41% yield). This reaction is carried out in aqueous solution under mild conditions and provides access to a useful statin side-chain building block.

Formation of Enantiopure 5-Substituted Oxazolidinones through Enzyme-Catalysed Kinetic Resolution of Epoxides

Halohydrin dehalogenase from Agrobacterium radiobacter catalyzed the enantioselective ring opening of terminal epoxides with cyanate as a nucleophile, yielding 5-substituted oxazolidinones in high yields and with high enantiopurity (69-98% ee). This is the first example of the biocatalytic conversion of a range of epoxides to the corresponding oxazolidinones.

Enzymatic Selectivity in Synthetic Methods

ummary This chapter contains sections titled: Alcalase‐catalysed Syntheses of Hydrophilic Di‐ and Tri‐peptides in Organic Solvents Selective Alkoxycarbonylation of 1α,25‐Dihydroxyvitamin D3 Diol Precursor with Candida antarctica Lipase B The Use of Lipase Enzymes for the Synthesis of Polymers and Polymer Intermediates Bioconversion of 3‐Cyanopyridine into Nicotinic Acid with Gordona terrae NDB1165 Enzyme‐promoted Desymmetrization of Prochiral Dinitriles Epoxide Hydrolase‐catalyzed Synthesis of (R)‐3‐Benzyloxy‐2‐methylpropane‐1,2‐diol One‐pot Biocatalytic Synthesis of Methyl (S)‐4‐Chloro‐3‐hydroxybutanoate and Methyl (S)‐4‐Cyano‐3‐hydroxybutanoate Reference