75885-58-4Relevant articles and documents
Regioselective ring cleavage of chiral β-trichloromethyl-β- propiolactone with organoaluminum compounds for the synthesis of optically active intermediates
Fujisawa, Tamotsu,Ito, Takatoshi,Nishiura, Shin,Shimizu, Makoto
, p. 9735 - 9738 (1998)
A novel alkylating ring cleavage reaction of enantiomerically pure β- trichloromethyl-β-propiolactone as a chiral building block with organoaluminum compounds provided ring-opened products with a chiral trichloromethyl carbinol moiety. A product was demonstrated to be used as an effective chiral synthon for the synthesis of chiral bioactive derivatives such as ipsdienol and sodium cilastatin.
A chiral dimethyl cyclopropanecarboxylic preparation method of the formamide
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Paragraph 0058; 0059; 0060; 0061; 0073; 0076; 0081; 0085, (2018/11/03)
The invention discloses a preparation method of chiral dimethyl cyclopropyl carboxamide. The method comprises a step of asymmetric cyclopropyl alkylation and a step of catalytic amidation of cyclopropyl formic ether, wherein in the step of asymmetric cyclopropyl alkylation, a cyclopropyl alkylation reaction is carried out on ethyl diazoacetate and isobutene under the catalysis of a chiral ligand complex of a cuprous salt so as to obtain (S)-dimethyl cyclopropyl formate; and in the step of catalytic amidation of cyclopropyl formic ether, an ammonolysis reaction is carried out on the (S)-dimethyl cyclopropyl formate by one step so as to directly obtain (S)-2,2-dimethyl cyclopropyl carboxamide, and refining the carboxamide with an alcohol so as to obtain the chiral dimethyl cyclopropyl carboxamide with chemical purity being greater than 99.5% and an e.e. value being greater than 99.5%. Thus, the method used for synthesizing the (S)-2,2-dimethyl cyclopropyl carboxamide is environment-friendly, simple, rapid and efficient.
Industrial production of S-2,2-dimethylcyclopropanecarboxamide with a novel recombinant R-amidase from Delftia tsuruhatensis
Yang, Zhong-Yi,Ni, Ye,Lu, Zhong-Yuan,Liao, Xiang-Ru,Zheng, Yu-Guo,Sun, Zhi-Hao
experimental part, p. 182 - 187 (2011/08/06)
R-Stereoselective amidase, a key enzyme responsible for the formation of chiral center of cilastatin, has been cloned from Delftia tsuruhatensis and expressed in Escherichia coli under T7 promoter. This recombinant amidase exhibits strict R-selectivity towards 2,2-dimethylcyclopropanecarboxamide (DMCPCA). The amidase activity of the engineered E. coli strain reached 2963 U/L in a 5-L bioreactor, which was 8.27 times higher than that of D. tsuruhatensis, and was further increased to 5255 U/L in a 100-L bioreactor. Using cell-free extract prepared from 1 kg (wet cell weight) of recombinant E. coli cells as catalyst, 60 kg of R,S-DMCPCA was resolved into S-DMCPCA (28.6 kg) and R-2,2-dimethylcyclopropanecarboxylic acid (R-DMCPCS 31.7 kg) in 18 h, and the enantiomeric excess (ee) value of S-DMCPCA reached 99.32%. During the purification process, 24.6 kg of S-DMCPCA was eluted from adsorption resin HZ801 with 80% (v/v) acetone, and then 20.5 kg of pure S-DMCPCA was obtained after concentration and crystallization, corresponding to a total yield of 34.2% from R,S-DMCPCA. Therefore, the industrial production process of S-DMCPCA was successfully established using recombinant R-amidase from D. tsuruhatensis.