84367-31-7Relevant 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).
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.
Asymmetric synthesis of l-carnitine from (R)-3-chloro-1,2-propanediol
Li, Xu Qin,Yang, Yun Xu,Wang, Wei Li,Hu, Bin,Xue, Hui Min,Zhang, Tian Yi,Zhang, Xue Tao
body text, p. 765 - 767 (2012/01/03)
A practical chemical synthesis of l-carnitine (1) has been accomplished from (R)-3-chloro-1,2-propanediol ((R)-4), which is a main by-product originated from (R,R)-Salen Co(III) catalyzed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin. (R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite ((R)-5). The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.