127913-44-4Relevant articles and documents
A One-Step Biocatalytic Process for (S)-4-Chloro-3-hydroxybutyronitrile using Halohydrin Dehalogenase: A Chiral Building Block for Atorvastatin
Wan, Nan-Wei,Liu, Zhi-Qiang,Xue, Feng,Shen, Zhen-Yang,Zheng, Yu-Guo
, p. 2446 - 2450 (2015)
(S)-4-Chloro-3-hydroxybutyronitrile [(S)-CHBN] was used as a chiral building block for the preparation of atorvastatin. In this study, (R,S)-epichlorohydrin [(R,S)-ECH] and 1,3-dichloro-2-propanol (1,3-DCP) were investigated to prepare (S)-CHBN by using the halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1. Preparing (S)-CHBN from (R,S)-ECH gave a modest enantiomeric excess (ee), whereas by using 1,3-DCP as the substrate, (S)-CHBN was obtained with 97.3 % ee after pH optimization. However, a low ee value and low yield of (S)-CHBN were obtained if the substrate concentration was increased to 10 g L-1. To obtain a higher ee value and yield, 16 mutants were constructed and screened. The variant W249F with improvements in activity and enantioselectivity was identified and applied at a 1,3-DCP loading of 10 g L-1, which gave (S)-CHBN in 86 % yield with 97.5 % ee in 1 h. This is the first report of a one-step biocatalytic process for the preparation of (S)-CHBN from prochiral 1,3-DCP.
A Cyanide-free Biocatalytic Process for Synthesis of Complementary Enantiomers of 4-Chloro-3-hydroxybutanenitrile From Allyl Chloride
Zheng, Daijun,Asano, Yasuhisa
, p. 4237 - 4242 (2021/08/25)
A biocatalyst used for selective ring scission of (±)-5-(chloromethyl)-4, 5-dihydroisoxazole to synthesize chiral (R)-4-chloro-3-hydroxybutanenitrile (90 % ee, 39 % isolated yield) and (S)-5-(chloromethyl)-4, 5-dihydroisoxazole (99 % ee, 39 % isolated yield) was developed by site-saturated mutagenesis on aldoxime dehydratase derived from Pseudomonas chlororaphis B23 (OxdA). The positive mutant (OxdA-L318I, E=68) improved the enantiomeric ratio E by 6-fold as compared to the wild type enzyme (OxdA-wild, E=11). The racemic precursor of (±)-5-(chloromethyl)-4, 5-dihydroisoxazole, used in the reaction, can be synthesized from readily available allyl chloride without utilizing highly toxic cyanide. The enantiopure (S)-5-(chloromethyl)-4, 5-dihydroisoxazole remaining in the kinetic resolution can be transformed into corresponding chiral (S)-4-chloro-3-hydroxybutanenitrile without loss of enantiomeric excess by treating it with triethylamine in acetonitrile (99 % ee, 72 % isolated yield) or catalysis of OxdA-wild enzyme (99 % ee, 88 % isolated yield).
Method for synthesizing butyrolactone derivative
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Paragraph 0026; 0027; 0028; 0029, (2018/05/16)
The invention discloses a method for synthesizing a butyrolactone derivative. The method comprises steps as follows: (1), after being activated by a titanium reagent, an epoxy compound represented asa formula (II) is subjected to an addition reaction by a Grignard reagent, and a compound represented as a formula (III) is obtained; (2), the compound represented as the formula (III) is subjected tocyano hydrolysis under the alkaline condition, and a carboxylic acid derivative represented as a formula (IV) is obtained; (3), the carboxylic acid derivative represented as the formula (IV) is subjected to a dehydration cyclization reaction, and the butyrolactone derivative represented as a formula (I) is obtained. The method has the advantages of being simple in synthesis step, low in production cost and high in functional group selectivity, regioselectivity and yield; the synthetic route is shown in the description.
