- Enantioselective Formal C?H Conjugate Addition of Acetanilides to β-Substituted Acrylates by Chiral Iridium Catalysts
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The Ir-catalyzed enantioselective reaction of substituted acetanilides with β-substituted α,β-unsaturated esters provided chiral 3,3-disubstituted propanoates in high yield with good-to-excellent enantiomeric excess (up to 99 % ee). This transformation, i
- Shibata, Takanori,Michino, Masamichi,Kurita, Hisaki,Tahara, Yu-Ki,Kanyiva, Kyalo Stephen
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Read Online
- A CHEMOENZYMATIC SYNTHESIS OF THE C10-C19 MOIETY OF FK506
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The strategy used in the synthesis of the C10-C19 segment of FK506 is described.
- Gu, Rui-Lin,Sih, Charles J.
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Read Online
- Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696
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LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.
- Gu, Xingxian,Zhao, Jibin,Chen, Like,Li, Yunzhong,Yu, Bo,Tian, Xiangguang,Min, Zhongcheng,Xu, Su,Gu, Huijuan,Sun, Junjie,Lu, Xiaoquan,Chang, Meng,Wang, Xufan,Zhao, Liqun,Ye, Shengqing,Yang, Hongwei,Tian, Yingtao,Gao, Feng,Gai, Yu,Jia, Guanghua,Wu, Jingjing,Wang, Yan,Zhang, Jianghua,Zhang, Xuesong,Liu, Weichun,Gu, Xin,Luo, Xi,Dong, Hai,Wang, Huaimin,Schenkel, Berthold,Venturoni, Francesco,Filipponi, Paolo,Guelat, Bertrand,Allmendinger, Thomas,Wietfeld, Bernhard,Hoehn, Pascale,Kovacic, Nikola,Hermann, Luca,Schlama, Thierry,Ruch, Thomas,Derrien, Nadine,Piechon, Philippe,Kleinbeck, Florian
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p. 6844 - 6853
(2020/06/04)
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- Modular 1,1′-Ferrocenediyl-cored P-Stereogenic Diphosphines: ′′JDayPhos′′ Series and its Use in Rhodium(I)-Catalyzed Hydrogenation
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A novel ferrocene-based P-stereogenic diphospine ligand series dubbed JDayPhos was developed, which rhodium(I) complexes of some of its members exhibited excellent enantioselectivity (up to >99% ee) and high activity in asymmetric hydrogenation of β-unsubstituted or -substituted itaconates and α-methylene-γ-oxo-carboxylates. (Figure presented.).
- Poklukar, Ga?per,Stephan, Michel,Mohar, Barbara
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supporting information
p. 2566 - 2570
(2018/05/16)
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- CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES FOR THE TREATMENT OF LIVER DISEASES
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The present invention relates to Compounds of Formula (I) or Formula (II) or a pharmaceutically acceptable salt, solvate or enantiomer thereof, wherein A, B, R1, R2, R3, R4, Q and V are as defined herein. The present invention also relates to pharmaceutical compositions comprising a Compound of Formula (I) or Formula (II) and to their use in therapy.
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Page/Page column 66; 67
(2018/06/06)
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- SPIROBENZYLAMINE-PHOSPHINE, PREPARATION METHOD THEREFOR AND USE THEREOF
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The present invention relates to a spirobenzylamine-phosphine, preparation method therefor and use thereof. The compound has a structure represented by formula (I), wherein n=0 to 3; R1, R2, R3, R4, R5, R6, R7, R8 and R9 having a value as defined in claim 1. Starting from the substituted 7-trifluoromesyloxy-7'-diarylphosphino-1, 1'-spiro-dihydroindene, the compound is synthesized in a two-step or three-step reactions. The new spirobenzylamine-phosphine is complexed with an iridium precursor and is subjected to ion exchange, to give an Iridium/spirobenzylamine-phosphine complex comprising various anions. The spiro benzyl amine-phosphine/Iridium complex according to the present invention may be used for catalyzing asymmetry hydrogenation of a variety of alpha-substituted acrylic acids, has high activity and enantio-selectivity, and has a good prospect of industrialization.
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Paragraph 0067
(2014/07/22)
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- Spirobenzylamine-Phosphine, Preparation Method Therefor And Use Thereof
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The present invention relates to a spirobenzylamine-phosphine, preparation method therefor and use thereof. The compound has a structure represented by formula (I), wherein n=0 to 3; R1, R2, R3, R4, R5, R6, R7, R8 and R9 having a value as defined in claim 1. Starting from the substituted 7-trifluoromesyloxy-7′-diarylphosphino-1,1′-spiro-dihydroindene, the compound is synthesized in a two-step or three-step reactions. The new spirobenzylamine-phosphine is complexed with an iridium precursor and is subjected to ion exchange, to give an Iridium/spirobenzylamine-phosphine complex comprising various anions. The spiro benzyl amine-phosphine/Iridium complex according to the present invention may be used for catalyzing asymmetry hydrogenation of a variety of alpha-substituted acrylic acids, has high activity and enantio-selectivity, and has a good prospect of industrialization.
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Paragraph 0080; 0081
(2014/07/22)
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- A convergent approach to (-)-callystatin a based on local symmetry
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The key is symmetry! A convergent synthetic approach of the highly cytotoxic natural product (-)-callystatin A was developed assembling three fragments through Julia-Kocienski olefination and Stille cross-coupling. The new strategy relies on a pivotal local symmetry of the target molecule. In this preliminary study, particular attention was devoted to facilitate the catalytic enantiocontrol of strategic stereogenic centers present in each of the fragments (see scheme). Copyright
- Candy, Mathieu,Tomas, Lo?c,Parat, Sabrina,Heran, Virginie,Bienaymé, Hugues,Pons, Jean-Marc,Bressy, Cyril
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p. 14267 - 14271
(2013/01/15)
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- A three-enzyme system involving an ene-reductase for generating valuable chiral building blocks
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The use of ene-reductase (ERED) enzymes for the asymmetric reduction of olefins offers a green, renewable alternative to metal-catalysed asymmetric reduction. We report herein the first example of an ERED-catalysed enantiospecific reduction carried out at large scale using a carbonyl reductase (CRED) enzyme in the cofactor recycle. This reaction has been paired with a hydrolase-mediated regioselective ester hydrolysis to generate a valuable chiral building block using a straightforward one-pot process. Copyright
- Mangan, David,Miskelly, Iain,Moody, Thomas S.
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p. 2185 - 2190,6
(2020/09/02)
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- Enantioselective hydrogenation of α-substituted acrylic acids catalyzed by iridium complexes with chiral spiro aminophosphine ligands
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Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids (see scheme). The complexes were highly active catalysts, showing turnover frequencies of up to 6000 h-1, and catalyst loadings could be reduced to 0.01 mol %. Copyright
- Zhu, Shou-Fei,Yu, Yan-Bo,Li, Shen,Wang, Li-Xin,Zhou, Qi-Lin
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supporting information; experimental part
p. 8872 - 8875
(2012/10/08)
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- Catalytic asymmetric alkynylation and arylation of aldehydes by an H 8-binaphthyl-based amino alcohol ligand
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A novel chiral H8-1,1'-binaphthyl-based amino alcohol ligand (1Ra,2S,3R)-2 has been synthesized and applied in the direct nucleophilic addition of organozincs (alkynylzinc and arylzinc prepared in situ) to aldehydes, yielding the corresponding optically active propargylic alcohols and diarylmethanols in high yields and good to excellent enantioselectivities. For the asymmetric arylation reaction, one catalyst (1Ra,2S,3R)-2 can afford both enantiomers of many pharmaceutically interesting diarylmethanols by a proper combination of various arylzinc reagents and aldehydes.
- Ruan, Jiwu,Lu, Gui,Xu, Lijing,Li, Yue-Ming,Chan, Albert S. C.
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scheme or table
p. 76 - 84
(2009/04/11)
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- Highly enantioselective hydrogenation of α-dehydroamino esters and itaconates with triphosphorous bidentate ligands and the unprecedented solvent effect thereof
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(Chemical Equation Presented) An X-ray diffraction experiment revealed an interesting triphosphorous bidentate coordination in a Pd(II) complex of a phosphine-phosphoramidite ligand 1, which showed excellent enantioselectivity (up to 99.4% ee) in Rh-catalyzed hydrogenation of α-dehydroamino esters in acetone. A dramatic solvent effect was found in the hydrogenation of itaconates, which induces opposite chiralities of the product with the same catalytic system by the use of different solvents (e.g., 99.6% ee (R) in TFE vs 71.2% ee (S) in methyl ethyl ketone).
- Zhang, Weicheng,Zhang, Xumu
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p. 1020 - 1023
(2008/02/01)
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- METHOD FOR THE PRODUCTION OF OPTICALLY ACTIVE ALKYL SUCCINIC ACID MONOALKYL ESTERS
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The invention relates to a method for producing optically active alkyl succinic acid monoalkyl esters of formula (I), wherein D and E independently represent H, C1-C10 alkyl, RC1-C10 alkyl, aryl, or alkylaryl.
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Page/Page column 8-9
(2008/06/13)
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- Highly enantioselective rhodium-catalyzed hydrogenation of 2-(2-methoxy-2-oxoethyl)acrylic acid - A convenient access of enantiomerically pure isoprenoid building blocks
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Asymmetric catalytic hydrogenation of 2-(2-methoxy-2-oxoethyl)acrylic acid (5) to give (2S)-4-methoxy-2-methyl-4-oxobutanoic acid [(S)-6] was studied. An enantiomeric excess of 99.7% ee was achieved with a catalyst formed in situ from [Rh(COD)2]BF4 and the chiral phosphite L2 in 1,2-dichloroethane as solvent. In addition, enzyme-catalyzed semi-saponification of dimethyl 2-methylsuccinate was investigated. Mono ester (S)-6 was transformed into a few compounds which can serve as C 5-building blocks in natural product syntheses. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Ostermeier, Markus,Brunner, Bernhard,Korff, Christian,Helmchen, Guenter
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p. 3453 - 3459
(2007/10/03)
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- Retroviral protease inhibitors
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N-heterocyclic moiety-containing hydroxyethylamine protease inhibitor compounds, methods for making the compounds, and intermediates useful in the method. Also, a method for inhibiting retroviral proteases and for treatment or prophylaxis of a retroviral infection.
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- Process for preparation of dicarboxylic acid monoesters
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A process for producing a dicarboxylic acid monoester which comprises subjecting a dicarboxylic acid monoester or an alkali metal salt of a dicarboxylic acid monoester and a metal alkoxide to transesterification in the presence of an organic solvent, or a process for producing a dicarboxylic acid monoester which comprises subjecting a dicarboxylic acid monoester or an alkali metal salt of a dicarboxylic acid monoester and an alcohol to transesterification in the presence of a metal alkoxide.
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- α-and β-amino acid hydroxyethlamino sulfonamides useful as retroviral protease inhibitors
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α- and β-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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- Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors
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PCT No. PCT/US94/09139 Sec. 371 Date Jan. 24, 1996 Sec. 102(e) Date Jan. 24, 1996 PCT Filed Aug. 23, 1994 PCT Pub. No. WO95/06030 PCT Pub. Date Mar. 2, 1995The invention relates to sulfonamide-containing hydroxyethylamine protease inhibitor compounds, their process of making, composition and method of use for inhibiting retroviral proteases such as human immunodeficiency virus.
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- alpha - and beta -amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
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alpha - and beta -amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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- Alpha- and beta-amino acid hydroxyethylamino sulfamic acid derivatives useful as retroviral protease inhibitors
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PCT No. PCT/US93/10552 Sec. 371 Date Feb. 2, 1995 Sec. 102(e) Date Feb. 2, 1995 PCT Filed Oct. 29, 1993 PCT Pub. No. WO94/10134 PCT Pub. Date May 11, 1994Certain Alpha- and Beta-amino acid hydroxyethylamino sulfamic acid derivatives represented by the following formula are useful as retroviral protease inhibitors:
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- Hybrid P-chiral diphosphines for asymmetric hydrogenation
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A family of diphosphine ligands has been prepared by Michael addition of o-anisylphenyl phosphide to diethyl vinylphosphonate and elaboration to phospholanes based on hexane-2,5-diol or mannitol; some preliminary results of Rh-complex catalysed hydrogenations are reported.
- Carmichael, Duncan,Doucet, Henri,Brown, John M.
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p. 261 - 262
(2007/10/03)
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- β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
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α- and β-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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- RETROVIRAL PROTEASE INHIBITORS
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N-heterocyclic moiety containing hydroxyethylamine compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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- Esterase catalyzed regio-and enantio-selective hydrolysis of substituted carboxylates
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Optically active α-substituted carboxylic acid derivatives were obtained with regio-and enantio-selective hydrolysis catalyzed by esterase from Pseudomonas putida MR-2068. Substrate specificities were summarized in empirical rule to predict the enantiopreferences of the esterase. High regio-selectivities were also discussed with binding models.
- Ozaki, Eiji,Sakashita, Keiichi
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p. 741 - 742
(2007/10/03)
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- RETROVIRAL PROTEASE INHIBITORS
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Urea-containing hydroxyethylamine peptide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
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- Enzymatic Preparation of Alkanedicarboxylic Acid Monoesters
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Hydrolysis of alkanedicarboxylic acid dimethyl esters using esterase from Pseudomonas putida MR-2068 gave exclusively pure monoesters.Hydrolytic activities were dependent on the carbon chain length of the substrates.This esterase also catalyzed enantio- and regio-selective hydrolysis of α-methylalkanedicarboxylic acid dimethyl esters.
- Ozaki, Eiji,Uragaki, Toshitaka,Sakashita, Keiichi,Sakimae, Akihiro
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p. 539 - 540
(2007/10/03)
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- Asymmetric Hydrogenation of Prochiral Alkenes Catalysed by Ruthenium Complexes of (R)-(+)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl
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Two chiral ruthenium(II) complexes containing (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl were found to be effective catalysts for the asymmetric hydrogenation of 2-acylaminoacrylic and 2-acylaminocinnamic acids under mild conditions, to afford N-acyl-(R)-α-amino acids with 49 - 95 percent optical purity.The differences between the asymmetric hydrogenations effected by RuII- and RhI-(R)-BINAP systems are discussed.Asymmetric hydrogenation of methylenesuccinic acid and its derivatives with Ru-(R)-BINAP is also described.
- Kawano, Hiroyuki,Ikariya, Takao,Ishii, Youichi,Saburi, Masahiko,Yoshikawa, Sadao,et al.
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p. 1571 - 1575
(2007/10/02)
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- RUTHENIUM(II)-BINAP COMPLEX CATALYZED ASYMMETRIC HYDROGENATION OF UNSATURATED DICARBOXYLIC ACIDS
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Asymmetric hydrogenation of unsaturated dicarboxylic acids employing ruthenium-BINAP complexes as catalyst gave optically active 2-alkylsuccinic acids with high enantioselectivities.
- Kawano, Hiroyuki,Ishii, Youichi,Ikariya, Takao,Saburi, Masahiko,Yoshikawa, Sadao,et. al
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p. 1905 - 1908
(2007/10/02)
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- Syntheses of Novel Sugar Phosphine Derivatives, and Homogeneous Hydrogenation Reaction with Their Rhodium Complexes
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Optically active diphenylphosphine derivatives, (1R,3R,4S,5R,6R)-6-cyano-5-diphenylphosphino-3,4-O-isopropylidene-2-oxabicycloheptane-3,4-diol (15) and its reduction product (17), were prepared by the cyclization of 12 or 13, which was obtained from a common sugar, D-glucose.These phosphines were used as ligands in the rhodium complex-catalyzed asymmetric hydrogenation of prochiral olefins.The rhodium complex catalyst which was constructed with 2 mol of 15 and 1 mol of rhodium(cyclooctene)2Cl (20) worked efficiently for the asymmetric hydrogenation of α-acetamidocinnamic acid (18) and itaconic acid (24) with 91.6percent ee-(S) and 69.6percent ee-(R), respectively.On the other hand, the rhodium complex constructed with 1 mol of 17 and 1 mol of 20 was less effective than that of 15, giving 39.0percent ee-(R) in the reaction with 18.Methyl esters of 18 and 24 were also hydrogenated using the complex of 15.Keywords - D-glucose; (1R,3R,4S,5R,6R)-6-cyano-5-diphenylphosphino-3,4-O-isopropylidene-2-oxabicycloheptane-3,4-diol; cyclobutane ring formation; chiral phosphine ligand; rhodium complex; asymmetric hydrogenation; enantioselectivity
- Saito, Setsuo,Nakamura, Yushin,Morita, Yutaka
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p. 5284 - 5293
(2007/10/02)
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- Derivatives of the potent angiotensin converting enzyme inhibotor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: Effect of changes at positions 2 and 5 of the hexanoic acid portion
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Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had an I50 against angiotensin converting enzyme of 1.0 x 10-9 M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.
- Almquist,Crase,Jennings-White,Meyer,Hoefle,Smith,Essenburg,Kaplan
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p. 1292 - 1299
(2007/10/02)
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