637-75-2Relevant articles and documents
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).
Preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as starting material
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Paragraph 0041-0049, (2019/11/12)
The invention discloses a preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as a starting material, and belongs to the field of medicinal chemistry. The method comprises the steps: using R-(-)-epoxychlorohydrin and hydrocyanic acid as starting materials, performing a reaction for synthesis of R-4-chloro-3-hydroxybutyronitrile under the action of a basic catalyst, thensynthesizing L-carnitine hydrochloride through two routes, purifying the L-carnitine hydrochloride prepared through the two routes further through resin so as to remove chloride ions, and preparing the final product L-carnitine. The two process routes are simple, the reaction conditions are mild, the operation is simple and feasible, and industrial production is convenient; the whole process is green and environmentally friendly, the reaction yield is high, three waste is little, no sodium cyanide is used, and no solid waste sodium salt is generated; and the hydrolysis by-product ammonium chloride has good quality, and can be sold as a by-product, and great economic benefits and market competitiveness are achieved.
Synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine
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Paragraph 0034; 0035, (2018/09/21)
The invention discloses a synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine. The synthesis method is characterized in that: (R)-epichlorohydrin serves as a starting material; the (R)-epichlorohydrin is firstly subjected to a ring-opening reaction by gaseous hydrogen cyanide; L-(-)-4-chlorine-3-hydroxybutyronitrile is obtained; then the L-(-)-4-chlorine-3-hydroxybutyronitrile is aminated by trimethylamine; and the L-(-)-chlorination 3-cyano-2-propyltrimethylamine is obtained. After the ring-opening reaction is completed, a small amount of hydrogen cyanide dissolved in a material needs to be replaced with nitrogen, and an end point is that a benzidine-cupric acetate test paper does not change to blue. According to the synthesis method, thegaseous hydrogen cyanide is firstly used to open a ring, and then the trimethylamine is used to perform amination, therefore the L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine with high yield and high content can be obtained; and by adopting the gaseous hydrogen cyanide to open the ring, only the nitrogen is needed to replace the gaseous hydrogen cyanide after the ring-opening reaction, the subsequent recovery of the trimethylamine is not affected, and the post-treatment process is greatly simplified.
