- Preparation of chiral synthon for HIV protease inhibitor: Stereoselective microbial reduction of N-protected α-aminochloroketone
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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.
- Patel, Ramesh N.,Banerjee, Amit,McNamee, Clyde G.,Brzozowski, David B.,Szarka, Laszlo J.
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Read Online
- Synthesis method of (2S, 3S)-3-(t-butyloxycarboryl amino)-1, 2-epoxy-4-phenylbutane
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The invention relates to the technical field of synthesis of drug intermediates, in particular to a synthesis method of (2S, 3S)-3-(t-butyloxycarboryl amino)-1, 2-epoxy-4-phenylbutane. The method comprises the following steps: condensing N-t-butyloxycarboryl-L-phenylalanine serving as a raw material with substituted phenol under the action of a condensing agent to obtain active ester 15; reacting the active ester 15 with a ylide reagent and alkali to obtain a sulfoxide ylide intermediate 16; reacting the sulfoxide ylide intermediate 16 with halide salt under the action of a catalyst to obtain a halogenated ketone intermediate 6; reducing the halogenated ketone intermediate 6 through a reducing agent under the action of a catalyst to obtain a halogenated methanol intermediate 7; and removing halogen acid from the halogenated methanol intermediate 7 under the action of alkali, and carrying out condensation cyclization to obtain the target product (2S, 3S)-3-(t-butyloxycarboryl amino)-1, 2-epoxy-4-phenylbutane. The synthesis method of the (2S, 3S)-3-(t-butyloxycarboryl amino)-1, 2-epoxy-4-phenylbutane, provided by the invention, has the characteristics of cheap and easily available initial raw materials, safe and controllable process and easiness in operation.
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- Synthetic method of HIV protease inhibitor intermediate compound
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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.
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Paragraph 0053-0056
(2021/03/06)
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- Preparation method of anti-HIV protease inhibitor intermediate
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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.
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Paragraph 0010; 0057-0060; 0065-0068
(2021/07/31)
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- Rh(iii)-Catalyzed diastereoselective transfer hydrogenation: An efficient entry to key intermediates of HIV protease inhibitors
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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.
- Chen, Gen-Qiang,Lang, Qi-Wei,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Wang, Fangyuan,Wu, Ting,Yin, Congcong,Zhang, Xumu,Zheng, Long-Sheng
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supporting information
p. 3119 - 3122
(2020/03/23)
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- Ketone Reductase Biocatalysis in the Synthesis of Chiral Intermediates Toward Generic Active Pharmaceutical Ingredients
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A range of generic active pharmaceutical ingredients were examined for potential chiral alcohol motifs and derivatives within their structures that could be employed as key synthetic intermediates. For seven generic active pharmaceutical ingredients (APIs), eight precursor ketones were acquired and then subjected to reduction by >400 commercially available ketone reductases from different suppliers. Positive screening results were achieved for five ketones screened, with multiple ketone reductases available for each successful ketone. Selectivity was typically >99.5% ee in most cases, including for the opposite enantiomer. The three best examples were then optimized and quickly scaled up to 1 L scale in high conversion and isolated yield while retaining selectivity of >99.5% ee for the desired chiral alcohol enantiomer. This work illustrates that where a wide range of enzymes are available, productive enzymes to give either alcohol enantiomer can be readily identified for many ketones and rapidly scaled up to produce chiral alcohols. This approach is particularly applicable to generating chiral API intermediates.
- Forsyth, Sian M.,Moseley, Jonathan D.,Raynbird, Marina Y.,Sampson, Joanne B.,Smith, Dan A.,Wells, Andrew S.
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- A process for the preparation method of the sulfuric acid [...] intermediates
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The invention discloses a method for preparing sulfuric acid [...] intermediate (2 R, 3 S) - 1, 2 - epoxy - 3 - tert-butoxycarbonyl amino - 4 - phenyl butane of the method, the method cheap L - phenylalanine as the starting material, by with the di-T-n-butyl reaction for protecting amino group, with acetic anhydride condensation, with hydrochloric acid after the occurrence of the chloro in the chiral catalyst under the effects of the asymmetric hydrogenation reduction, finally cyclization under basic conditions to obtain the target product. The present invention provides of sulfuric acid is an important intermediate [...] (2 R, 3 S) - 1, 2 - epoxy - 3 - tert-butoxycarbonyl amino - 4 - phenyl butane preparation method of the raw material is cheap, mild reaction conditions, the synthesis efficiency is high, it is suitable for industrial production, in order to prepare sulfuric acid [...] and intermediate provides a highly efficient way.
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- 4-amino-N-[ (2R, 3S) - 3-amino-2-hydroxy-4-phenyl-butyl]-N- isobutyl-benzene sulfonaide preparation method
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The invention discloses a method for preparing 4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-benzene butyl]-N-isobutyl benzsulfamide. The method comprises the following steps: S1: enabling L-phenylalanine and diazomethane to react to obtain a diazo methyl ketone intermediate product, and enabling the diazo methyl ketone intermediate product and haloid acid to react to obtain a compound A; S2, conducting carbonyl deoxidation on the compound A to obtain a compound B; S3, under the existence of iso-butylamine, conducting cyclization reaction and ring-opening reaction on the compound B in sequence to obtain a compound C; S4, enabling the compound C and nitrobenzenesulfonyl chloride to react to obtain a compound D; S5, conducting nitro reduction on the compound D to obtain the 4-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-benzene butyl]-N-isobutyl benzsulfamide. The method is simple in course, low in cost, mild in condition, and higher in intermediate product stability, and is beneficial for industrial application.
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- Chiral chlorohydrins from the biocatalyzed reduction of chloroketones: Chiral building blocks for antiretroviral drugs
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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.
- 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.
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p. 984 - 992
(2015/03/18)
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- Crystalline Darunavir
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The present invention relates to a non-solvated crystalline Darunavir, process for its preparation and pharmaceutical composition comprising it. The present invention also relates to a process for the preparation of amorphous Darunavir from a non-solvated crystalline Darunavir.
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Paragraph 0047
(2014/12/09)
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- CRYSTALLINE DARUNAVIR
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The present invention relates to a non-solvated crystalline Darunavir, process for its preparation and pharmaceutical composition comprising it. The present invention also relates to a process for the preparation of amorphous Darunavir from a non-solvated crystalline Darunavir.
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- Al(OtBu)3 as an effective catalyst for the enhancement of Meerwein-Ponndorf-Verley (MPV) reductions
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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.
- Flack, Kyle,Kitagawa, Kristen,Pollet, Pamela,Eckert, Charles A.,Richman, Kent,Stringer, Joy,Dubay, William,Liotta, Charles L.
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experimental part
p. 1301 - 1306
(2012/09/07)
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- REDUCTION OF ALDEHYDES AND KETONES TO ALCOHOLS
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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.
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Page/Page column 20
(2011/06/16)
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- Synthesis of deuterium-labelled fosamprenavir calcium
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This study describes the synthesis of deuterium-labelled fosamprenavir calcium. The stable isotopic-labelled compound was prepared starting from L-phenylalanine in 18 steps with a 9% overall yield. Copyright
- Shi, Lei,Chen, Liping,Chen, Ryan,Chen, Liqin
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experimental part
p. 148 - 152
(2011/07/31)
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- Production method of aminochlorohydrin sulfate
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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.
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Page/Page column 21
(2010/11/26)
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- PROCESS FOR ASYMMETRIC CATALYTIC HYDROGENATION
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The invention provides a process for preparing optically active 1,2-haloalcohols from an α-haloketone by asymmetric catalytic hydrogenation of a-haloketones comprising providing a substrate comprising an a-haloketone and contacting the substrate with a hydrogenation reagent under conditions effective for hydrogenation of the substrate in the presence of a catalyst comprising ruthenium or rhodium coordinated to a bisphosphine ligand.
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Page/Page column 7; 15-16
(2008/06/13)
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- One-Carbon Chain Extension of Esters to α-Chloroketones: A Safer Route without Diazomethane
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The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 °C affords the chain-extended β-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding α-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected α-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to α-chloroketones that avoids the use of toxic and explosive diazomethane.
- Wang, Dengjin,Schwinden, Mark D.,Radesca, Lilian,Patel, Bharat,Kronenthal, David,Huang, Ming-Hsing,Nugent, William A.
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p. 1629 - 1633
(2007/10/03)
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- Stereoselective synthesis of photoreactive peptidomimetic γ-secretase inhibitors
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The first asymmetric synthesis of novel, potent photoreactive γ-secretase inhibitors 2 and 3 has been accomplished. Two Stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing γ-secretase activity in the plasma membrane of intact cells.
- Chun, Jiong,Yin, Ye Ingrid,Yang, Guangli,Tarassishin, Leonid,Li, Yue-Ming
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p. 7344 - 7347
(2007/10/03)
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- Asymmetric transfer hydrogenation of α-aminoalkyl α′-chloromethyl ketones with chiral Rh complexes
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Asymmetric transfer hydrogenation of N-substituted (3S)-3-amino-1-chloro-4- phenyl-2-butanones in the presence of Cp*RhCl[(R,R)-Tsdpen] (S/C = 1000) with a mixture of formic acid/triethylamine gave N-substituted (2R,3S)-3-amino-1-chloro-2-hydroxy-4-phenylbutanes with up to 93% de in a quantitative yield, and reduction with the enantiomeric catalyst Cp*RhCl[(S,S)-Tsdpen] gave (2S.3S)-diastereomeric alcohol with up to 96% de.
- Hamada, Takayuki,Torii, Takayoshi,Onishi, Tomoyuki,Izawa, Kunisuke,Ikariya, Takao
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p. 7391 - 7394
(2007/10/03)
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- Process for the preparation of alpha' chloroketones
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The present invention relates to a process for the preparation of α′ chloroketones, such as 4-phenyl-3-t-butyloxy-carbonylamino)-2-keto-1-chlorobutane by reacting certain aryl amino acid esters, e.g. N-(2-t-butoxycarbonyl)-L-phenylalanine-4-nitrophenyl ester, with a sulfur ylide compound to form the corresponding keto ylide compound which is then treated with a source of chloride and an organic acid.
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- Production method of beta-amino-alpha-hydroxycarboxylic acid
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The present invention provides a production method of an optically active β-amino-α-hydroxycarboxylic acid, which includes the following steps (a)-(c): (a) treating an optically active N-carbamate protected β-amino epoxide with an acid to give an optically active 5-hydroxymethyl-2-oxazolidinone; (b) oxidizing the resulting compound in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy and hypochlorite to give an optically active 4-benzyl-2-oxo-5-oxazolidinecarboxylic acid; and (c) treating the 4-benzyl-2-oxo-5-oxazolidinecarboxylic acid with a base, and a production method of an optically active N-carbamate protected β-amino-α-hydroxycarboxylic acid which includes protection of the amino group with a carbamate type protecting group. The industrial production method of the present invention can produce these compounds efficiently.
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- Process for reducing α-amino ketones
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The present invention has its objects to provide a method for reducing α-aminoketone derivatives under mild conditions with high stereoselectivity. This invention is a method for reducing α-aminoketone which comprises reacting an a-aminoketone derivative of general formula (1) with a compound prepared from an organoaluminum compound of general formula (4), a sulfonic acid derivative of general formula (5), and an alcohol compound of general formula (6) to give an α-aminoalcohol derivative of general formula (7)
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- METHOD FOR PURIFYING AND ISOLATING (2S,3S)- OR (2R,3S)-HALOHYDRIN DERIVATIVES
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The present invention has for its object to provide a practical method for the purification and isolation on a commercial scale of said compound (1) or compound (2) in good yield and with high quality. The present invention provides a purification/isolation method of a (2S,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (1) or a (2R,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (2) which comprises, for the purpose of removing contaminant impurity from a mixture containing at least one of said compounds(1) and (2), causing the objective compound (1) or compound (2) to be crystallized in the presence of a solvent comprised of a hydrocarbon solvent and then collecting the obtained crystals.
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- Process for the reduction of carbonyl compounds
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PCT No. PCT/JP97/00189 Sec. 371 Date Dec. 29, 1997 Sec. 102(e) Date Dec. 29, 1997 PCT Filed Jan. 29, 1997 PCT Pub. No. WO97/28105 PCT Pub. Date Aug. 7, 1997The present invention provides a process for reducing carbonyl compounds to hydroxy compounds, in particular stereoselectively reducing alpha -aminohaloketone derivatives, under mild conditions in an easy and simple manner, which comprises reacting a carbonyl compound of the general formula (1) with an organoaluminum compound of the general formula (4) to provide the corresponding alcohol compound of the general formula (5).
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- Biocatalytic synthesis of chiral intermediates for antiviral and antihypertensive drugs
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The chiral intermediate (1S,2R) [3-chloro-2-hydroxy-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 2a was prepared for the total synthesis of a human immunodeficiency virus protease inhibitor, BMS-186318. The stereoselective reduction of (1S) [3-chloro-2-oxo-1(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 1 was carried out using microbial cultures, among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a. A reaction yield of 80%, enantiomeric excess (e.e.) of 99.8%, and diastereomeric purity of 99% were obtained for chiral alcohol 2a. Chiral L-6-hydroxy norleucine 3, an intermediate in the synthesis of antihypertensive drug, was prepared by reductive amination of 2-keto-6-hydroxyhexanoic acid 4 using beef liver glutamate dehydrogenase. The cofactor NADH required for this reaction was regenerated using glucose dehydrogenase from Bacillus sp. A reaction yield of 80% and e.e. of 99.5% were obtained for L-6-hydroxynorleucine 3. To avoid the lengthy chemical synthesis of the ketoacid, a second route was developed in which racemic 6-hydroxynorleucine [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 5] was treated with D-amino acid oxidase from Trigonopsis variabilis to selectively convert the D-isomer of racemic 6-hydroxynorleucine to 2-keto-6-hydroxyhexanoic acid 4 and L-6-hydroxynorleucine 3. Subsequently, the 2-keto-6-hydroxyhexanoic acid 4 was converted to L-6-hydroxynorleucine by reductive amination using glutamate dehydrogenase. A reaction yield of 98% and an e.e. of 99.5% were obtained.
- Patel, Ramesh N.
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p. 1275 - 1281
(2007/10/03)
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- Process for producing 1,2-epoxy-3-amino-4-phenylbutane derivatives
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The present invention provides a process for producing 1,2-epoxy-3-amino-4-phenylbutane derivatives which comprises treating a 1-halo-2-hydroxy-3-amino-4-phenylbutane derivative with a base in an aprotic polar organic solvent or a mixed solvent composed of an aprotic polar organic solvent and water and then causing the resulting epoxide to crystallize out from a mixed solvent composed of an aprotic polar organic solvent and water.
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- Practical, stereoselective synthesis of palinavir, a potent HIV protease inhibitor
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Palinavir is a potent peptidomimetic-based HIV protease inhibitor. We have developed a highly convergent and stereoselective synthesis which is amenable to the preparation of multikilogram quantities of this compound. The synthetic sequence proceeds in 24 distinct chemical steps (with several integrated, multistep operations) from commercially available starting materials. No chromatographies are required throughout the process, and the final product is purified by crystallization of its dihydrochloride salt to >99% homogeneity.
- Beaulieu, Pierre L.,Lavallee, Pierre,Abraham, Abraham,Anderson, Paul C.,Boucher, Colette,Bousquet, Yves,Duceppe, Jean-Simon,Gillard, James,Gorys, Vida,Grand-Maitre, Chantal,Grenier, Louis,Guindon, Yvan,Guse, Ingrid,Plamondon, Louis,Soucy, Francois,Valois, Serge,Wernic, Dominik,Yoakim, Christiane
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p. 3440 - 3448
(2007/10/03)
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- A practical method for the preparation of α'-chloroketones of N-carbanaate protected-α-aminoacids
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A practical method for the preparation of α-N-BOC-epoxides from protected amino acid esters based on the Kowalski homologation reaction is described. This procedure can be readily performed on a large scale without the use of hazardous reagents and has allowed preparation of epoxides 3 in multi-kilogram quantities.
- Chen, Ping,Cheng, Peter T. W.,Spergel, Steven H.,Zahler, Robert,Wang, Xuebao,Thottathil, John,Barrish, Joel C.,Polniaszek, Richard P.
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p. 3175 - 3178
(2007/10/03)
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- Retrocarbamate protease inhibitors
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The invention discloses compounds of the formula STR1 are disclosed as HIV protease inhibitors.
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- Aminodiol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR
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A series of HIV protease inhibitors containing a novel C2 symmetrical "aminodiol" core structure were prepared from amino acid starting materials.The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds.Optimization of the structure-activity in this series led to aminodiol 9a (Ki = 100 nM; ED50(HIV-1) = 80 nM) containing P1/P1' benzyl and P2/P2' Boc substituents.Compound 9a is a selective inhibito r of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin.In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs.After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40percent) and a promising plasma elimination half-life (4 h).
- Barrish, Joel C.,Gordon, Eric,Alam, Masud,Lin, Pin-Fang,Bisacchi, Gregory S.,et al.
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p. 1758 - 1768
(2007/10/02)
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