162536-40-5Relevant articles and documents
Al(OtBu)3 as an effective catalyst for the enhancement of Meerwein-Ponndorf-Verley (MPV) reductions
Flack, Kyle,Kitagawa, Kristen,Pollet, Pamela,Eckert, Charles A.,Richman, Kent,Stringer, Joy,Dubay, William,Liotta, Charles L.
, p. 1301 - 1306 (2012)
The Meerwein-Ponndorf-Verley (MPV) reduction of aldehydes and ketones has been the cornerstone in many multistep syntheses. Herein we report the use of Al(OtBu)3 instead of the commonly used Al(OiPr)3 which results in a dramatic rate increase and significantly lower catalyst loading for the reduction of (1) model compounds benzaldehyde and acetophenone, and (2) N-(tert-butyloxycarbonyl)-(3S)-3-amino-1-chloro-4-phenyl-2-butanone or (S)-CMK, a key intermediate in HIV protease inhibitor synthesis.
Preparation method of anti-HIV protease inhibitor intermediate
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Paragraph 0010; 0043-0046; 0049-0052, (2021/07/31)
The invention relates to the technical field of medicine preparation, in particular to a preparation method of an anti-HIV protease inhibitor intermediate. According to the invention, the anti-HIV protease inhibitor intermediate disclosed as a formula II or a formula III shown in the description is obtained by reacting a compound shown in a formula I defined in the description as a raw material, a catalyst A or catalyst B serving as a catalyst and dichloromethane and an aprotic polar solvent serving as a mixed solvent in the presence of formate. Firstly, the preparation method of the novel anti-HIV protease inhibitor intermediate, which is mild in condition, safe in process and suitable for industrial production, is created, and the reaction conditions are further explored and optimized, so that the reaction yield and purity are greatly improved.
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.
Chiral chlorohydrins from the biocatalyzed reduction of chloroketones: Chiral building blocks for antiretroviral drugs
De Miranda, Amanda S.,Simon, Robert C.,Grischek, Barbara,De Paula, Gabriel C.,Horta, Bruno A. C.,De Miranda, Leandro S. M.,Kroutil, Wolfgang,Kappe, C. Oliver,De Souza, Rodrigo O. M. A.
, p. 984 - 992 (2015/03/18)
E. coli cells that contain overexpressed alcohol dehydrogenases (ADHs) were screened as biocatalysts for the stereoselective reduction of chloroketones 5 a-d, the corresponding halohydrins 6 a-d of which are building blocks in the synthesis of antiretroviral drugs. Among them, ADH from Sphingobium yanoikuyae was found to reduce chloroketone 5 c with a high stereoselectivity (90 % de) and conversion (85 %) to furnish threo halohydrin (R,S)-6 c. ADH from Ralstonia sp. (RasADH) was able to reduce 5 a and 5 b with complementary diastereoselectivity to provide access to both threo and erythro halohydrins through "substrate-based" stereocontrol. The RasADH-catalyzed reductions were optimized to provide (R,S)-6 a with 98 % conversion and 84 % diastereomeric excess (de) and (S,S)-6 b with 95 % conversion and 86 % de. Molecular modeling studies showed that 5 b, which features a carboxybenzyl protecting group, is able to bind to the enzyme catalytic site in an "inverted" mode in comparison to tert-butyloxycarbonyl- and methyloxycarbonyl-protected substrates 5 a and 5 c, which sheds light on the observed switching of the stereopreference. RasADH-catalyzed reductions were optimized to provide (R,S)-6 a with 98 % conversion and 84 % de and (S,S)-6 b with 95 % conversion and 86 % de.