162536-40-5

Usage

Uses

Used in Pharmaceutical Synthesis:
(2R,3S)-3-(tert-Butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane is used as a key intermediate in the synthesis of pharmaceuticals for its potential to contribute to the development of new drug molecules with therapeutic applications. The Boc protecting group allows for selective reactions and subsequent deprotection steps in complex organic synthesis processes.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (2R,3S)-3-(tert-Butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane is utilized as a chiral building block for the design and synthesis of enantiomerically pure compounds. Its unique stereochemistry allows researchers to explore the effects of stereoselectivity on drug efficacy and safety, leading to the discovery of more effective and targeted therapeutic agents.
Used in Organic Chemistry Education:
(2R,3S)-3-(tert-Butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane serves as a valuable teaching tool in organic chemistry, illustrating the concepts of chirality, stereochemistry, and protecting groups. It can be used in laboratory exercises to demonstrate the synthesis and manipulation of complex organic molecules, providing students with hands-on experience in the techniques and strategies used in modern organic synthesis.

InChI:InChI=1/C15H22ClNO3/c1-15(2,3)20-14(19)17-12(13(18)10-16)9-11-7-5-4-6-8-11/h4-8,12-13,18H,9-10H2,1-3H3,(H,17,19)/t12-,13-/m0/s1

Upstream product

• 102123-74-0 (S)-tert-butyl (4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate 
• 171815-94-4 (3S)-3-dibenzylamino-1-chloro-2-oxo-4-phenylbutane 
• 63-91-2 L-phenylalanine 
• 111138-83-1 N,N-dibenzyl-L-phenylalanine benzyl ester 
• 369362-96-9 (2S,3R)-2-amino-4-chloro-1-phenylbutan-3-ol hydrochloride 
• 24424-99-5 di-tert-butyl dicarbonate 
• 934971-02-5 (2R,3S)-1-chloro-3-amino-4-phenyl-2-butanol sulfuric acid salt 
• 67729-36-6 Boc-Phe-O-COO-isoBu 
• 60398-41-6 (3S)-tert-butyl 1-benzyl-3-diazo-2-oxopropylcarbamate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 51987-73-6 (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester 

Downstream Products

• 1192510-20-5 methyl [(2S)-3,3-dimethyl-1-({(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}amino)-1-oxobutan-2-yl]carbamate 
• 198905-04-3 1-[4-(pyridine-2-yl)-phenyl]-4(S)-hydroxy-2-N-tert-butoxycarbonylamino-5(S)-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-6-phenyl-2-azahexane 
• 198904-31-3 atazanavir 
• 229975-97-7 atazanavir sulphate 
• 369362-96-9 (2S,3R)-2-amino-4-chloro-1-phenylbutan-3-ol hydrochloride 
• 98760-08-8 (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane 
• 162677-31-8 {(1S,2R)-1-Benzyl-3-[benzyl-((2S,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester 
• 161302-38-1 <(S,S)-3-<<(R,S)-3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-phenylbutyl>amino>-2-hydroxy-1-(phenylmethyl)propyl>carbamic acid 1,1-dimethylethyl ester 
• 161302-38-1 (1S-(1R*,2R)(3S*))-<3-<<3-<<(1,1-dimethylethoxy)carbonyl>amino>-2-hydroxy-4-phenylbutyl>amino>-2-hydroxy-1-(phenylmethyl)propyl>carbamic acid 1,1-dimethylethyl ester 
• 162541-34-6 ((1S,2S)-3-Amino-1-benzyl-2-hydroxy-propyl)-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Al(OtBu)3 as an effective catalyst for the enhancement of Meerwein-Ponndorf-Verley (MPV) reductions

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.

Diastereoselective microbial reduction of (S)-[3-chloro-2-oxo-1- (phenylmethyl)propyl]carbamic acid, 1,1-dimethylethyl ester

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 the HIV protease inhibitor Atazanavir. The diastereoselective 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 Rhodococcus, Brevibacterium, and Hansenula strains reduced 1 to 2a. Three strains of Rhodococcus gave >90% yield. A diastereomeric purity of >98% and enantiomeric excess of >99.3% were obtained for alcohol 2a.

Preparation method of anti-HIV protease inhibitor intermediate

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.

Synthetic method of HIV protease inhibitor intermediate compound

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

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.

A (2 R, 3 S) - 1 - chloro - 3 - tert-butoxy amide - 4 - phenyl - 2 - butanol preparation method

The invention provides a preparation method for (2R,3S)-1-chlorine-3-tert-butoxycarbonylamino-4-phenyl-2-butanol. The preparation method comprises the steps that L-phenylalanine is taken as raw materials, protected by adopting benzyl, esterified and then catalyzed through NMM to generate a mixed anhydride compound, the mixed anhydride compound reacts with diazomethane to generate diazoketone, a reduction reaction and palladium carbon reduction are performed, and finally the intermediate (2R,3S)-1-chlorine-3-tert-butoxycarbonylamino-4-phenyl-2-butanol is obtained. According to the preparation method, the low-cost benzyl is adopted to protect amidogen, the synthetic route is reasonable, the operation technology is simple, safe and high in yield, industrialization can be well achieved, and the production efficiency is improved.

Chiral chlorohydrins from the biocatalyzed reduction of chloroketones: Chiral building blocks for antiretroviral drugs

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.

REDUCTION OF ALDEHYDES AND KETONES TO ALCOHOLS

The embodiments described herein provide a reduction of an aldehyde or a ketone, such as a Meerwein-Ponnorf-Verley (MPV) reaction of an aldehyde or ketone. In some embodiments, the reaction occurs in the presence of A1[OC(CH3)3]. In some embodiments, the reaction occurs in the presence of an aprotic solvent. In some embodiments, the aldehyde or ketone is an amino aldehyde or an amino ketone wherein the amine is group is protected such that the nitrogen of the amine has no proton. Other embodiments related to compositions and compounds related to the reduction reaction, or to the preparation or use of the aldehyde, the ketone, or the resulting alcohol.

Carbonyl reductase, gene thereof and method of using the same

The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant. Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.

Production method of aminochlorohydrin sulfate

Highly pure (2R,3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane or (2S,3R)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane may be conveniently produced in high yield by: (a) reacting compound (1) with lithiumchloromethane to give compound (2) and at least a byproduct; (b) dissolving compound (2) and the byproduct in a polar solvent and adding water to the solution to precipitate compound (2) as crystals; (c) reducing the crystals of compound (2) to give compound (3) and at least its diastereomer as an impurity; (d) adding sulfuric acid thereto to give compound (4) and at least its diastereomer as an impurity; and (e) precipitating compound (4) as crystals from a solution containing acetic acid ester or acetic acid ester.