165727-45-7Relevant articles and documents
Preparation of chiral synthon for HIV protease inhibitor: Stereoselective microbial reduction of N-protected α-aminochloroketone
Patel, Ramesh N.,Banerjee, Amit,McNamee, Clyde G.,Brzozowski, David B.,Szarka, Laszlo J.
, p. 2547 - 2552 (1997)
The chiral intermediate (1S,2R) [3-chloro-2-hydroxy-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 2a was prepared for the total synthesis of an HIV protease inhibitor, BMS-186318. The stereoselective reduction of (1S) [3-chloro-2-oxo-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 1 was carried out using microbial cultures among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a. A reaction yield of 80% was obtained. The optical purity of 99.8% and the diastereomeric purity of 99% were obtained for chiral alcohol 2a.
Synthetic method of HIV protease inhibitor intermediate compound
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Paragraph 0053-0056, (2021/03/06)
The invention is suitable for the technical field of drug synthesis, and provides a synthesis method of an HIV protease inhibitor intermediate compound. The method comprises the following steps: underthe protection of argon, adding a catalyst and hydrogen source mixture into a compound 1a in a reaction solvent, and carrying out asymmetric transfer hydrogenation reaction to obtain the HIV proteaseinhibitor intermediate compound 2a or 2a'. The synthetic route is shown as follows: the group R is one of tert-butyloxycarboryl, carbobenzoxy, p-toluenesulfonyl, acetyl and benzoyl. The asymmetric transfer hydrogenation technology is utilized, compared with existing similar intermediates, the stereoselectivity and yield of the synthesized HIV protease inhibitor intermediate compound can be greatly improved, and the diastereoselectivity ratio of the product reaches 94:6; and in addition, the catalyst is low in dosage and high in catalytic efficiency, reaction activity is improved, raw materialloss is low, the whole process is rapid, simple and convenient, and cost is greatly reduced.
Rh(iii)-Catalyzed diastereoselective transfer hydrogenation: An efficient entry to key intermediates of HIV protease inhibitors
Chen, Gen-Qiang,Lang, Qi-Wei,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Wang, Fangyuan,Wu, Ting,Yin, Congcong,Zhang, Xumu,Zheng, Long-Sheng
supporting information, p. 3119 - 3122 (2020/03/23)
A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α′-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99?:?1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.