- Primary Alcohols via Nickel Pentacarboxycyclopentadienyl Diamide Catalyzed Hydrosilylation of Terminal Epoxides
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The efficient and regioselective hydrosilylation of epoxides co-catalyzed by a pentacarboxycyclopentadienyl (PCCP) diamide nickel complex and Lewis acid is reported. This method allows for the reductive opening of terminal, monosubstituted epoxides to form unbranched, primary alcohols. A range of substrates including both terminal and nonterminal epoxides are shown to work, and a mechanistic rationale is provided. This work represents the first use of a PCCP derivative as a ligand for transition-metal catalysis.
- Lambert, Tristan H.,Steiniger, Keri A.
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p. 8013 - 8017
(2021/10/25)
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- Asymmetric Synthesis of N-Substituted α-Amino Esters from α-Ketoesters via Imine Reductase-Catalyzed Reductive Amination
-
N-Substituted α-amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N-substituted α-amino esters through the direct reductive coupling of α-ketoesters and amines employing sequence diverse metagenomic imine reductases (IREDs). Both enantiomers of N-substituted α-amino esters were obtained with high conversion and excellent enantioselectivity under mild reaction conditions. In addition >20 different preparative scale transformations were performed highlighting the scalability of this system.
- Yao, Peiyuan,Marshall, James R.,Xu, Zefei,Lim, Jesmine,Charnock, Simon J.,Zhu, Dunming,Turner, Nicholas J.
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supporting information
p. 8717 - 8721
(2021/03/16)
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- Erbium-Catalyzed Regioselective Isomerization-Cobalt-Catalyzed Transfer Hydrogenation Sequence for the Synthesis of Anti-Markovnikov Alcohols from Epoxides under Mild Conditions
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Herein, we report an efficient isomerization-transfer hydrogenation reaction sequence based on a cobalt pincer catalyst (1 mol %), which allows the synthesis of a series of anti-Markovnikov alcohols from terminal and internal epoxides under mild reaction conditions (≤55 °C, 8 h) at low catalyst loading. The reaction proceeds by Lewis acid (3 mol % Er(OTf)3)-catalyzed epoxide isomerization and subsequent cobalt-catalyzed transfer hydrogenation using ammonia borane as the hydrogen source. The general applicability of this methodology is highlighted by the synthesis of 43 alcohols from epoxides. A variety of terminal (23 examples) and 1,2-disubstituted internal epoxides (14 examples) bearing different functional groups are converted to the desired anti-Markovnikov alcohols in excellent selectivity and yields of up to 98%. For selected examples, it is shown that the reaction can be performed on a preparative scale up to 50 mmol. Notably, the isomerization step proceeds via the most stable carbocation. Thus, the regiochemistry is controlled by stereoelectronic effects. As a result, in some cases, rearrangement of the carbon framework is observed when tri-and tetra-substituted epoxides (6 examples) are converted. A variety of functional groups are tolerated under the reaction conditions even though aldehydes and ketones are also reduced to the respective alcohols under the reaction conditions. Mechanistic studies and control experiments were used to investigate the role of the Lewis acid in the reaction. Besides acting as the catalyst for the epoxide isomerization, the Lewis acid was found to facilitate the dehydrogenation of the hydrogen donor, which enhances the rate of the transfer hydrogenation step. These experiments additionally indicate the direct transfer of hydrogen from the amine borane in the reduction step.
- Liu, Xin,Longwitz, Lars,Spiegelberg, Brian,T?njes, Jan,Beweries, Torsten,Werner, Thomas
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p. 13659 - 13667
(2020/11/30)
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- SELECTIVE INHIBITORS OF NLRP3 INFLAMMASOME
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The present disclosure relates to compounds of Formula (I): (I); and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as autoinflammatory and autoimmune diseases and cancers.
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-
Paragraph 0466; 0485; 0492
(2019/02/15)
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- MACROCYCLIC INHIBITORS OF HEPATITIS C PROTEASE
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The invention provides macrocyclic compounds inhibitory to the Hepatitis C viral protease, compositions and combinations including the compounds, methods of treatment of conditions wherein inhibition of the Hepatitis C viral protease is medically indicated, and methods of treatment of a Hepatitis C viral infection in a human patient.
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Page/Page column 93
(2010/04/25)
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- Manganese-promoted regioselective ring-opening of 2,3-epoxy acid derivatives: a new route to α-hydroxy acid derivatives
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A simple and general methodology directed towards the synthesis 3-aryl-2-hydroxy amides, or esters with total regioselectivity from the easily available 2,3-epoxy amides or esters, promoted by active manganese is described. Utilizing enantiopure epoxy amides as starting materials, the corresponding 3-aryl-2-hydroxy amides in enantiopure form are also available. Some synthetic applications of selected examples of 3-aryl-2-hydroxy carboxylic acid derivatives are shown. A mechanism has been proposed to explain this novel reaction.
- Concellon, Jose M.,Bernad, Pablo L.,Rodriguez-Solla, Humberto,Diaz, Pamela
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experimental part
p. 2178 - 2184
(2009/12/31)
-
- Diphosphines and Metal Complexes
-
Compounds of the formula I or I′, where the radicals R1 are each, independently of one another, a hydrogen atom or C1-C4-alkyl and R′1, is C1-C4-alkyl; X1 and X2 are each, independently of one another, a sec-phosphino group; R2 is hydrogen, R01R02R03Si— is halogen-, hydroxyl-, C1-C8-alkoxy- or R04R05N-substituted C1-C18-acyl or is R06—X01—C(O)—; R01, R02 and R03 are each, independently of one another, C1-C12-alkyl, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-aryl or C7-C12-aralkyl; R04 and R05 are each, independently of one another, hydrogen, C1-C12-alkyl, C3-C8-cycloalkyl, C6-C10-aryl or C7-C12-aralkyl, or R04 and R05 together are trimethylene, tetramethylene, pentamethylene or 3-oxapentylene; R06 is C1-C18-alkyl, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkyl, C6-C10-aryl or C7-C12-aralkyl; X01 is —O— or —NH—; T is C-bonded C3-C20-heteroarylene; v is 0 or an integer from 1 to 4; X1 in the heteroring of the heteroarylene is bound in the ortho position relative to the T—C* bond; and * indicates a mixture of racemic or enantiomerically pure diastereomers or pure racemic or enantiomerically pure diastereomers. The compounds are excellent chiral ligands for metal complexes as enantioselective catalysts for the hydrogenation of prochiral organic compounds.
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Page/Page column 15
(2009/10/31)
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- Magnetically separable Pd catalyst for highly selective epoxide hydrogenolysis under mild conditions
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A magnetically separable palladium catalyst was synthesized simply through a sol-gel process incorporating palladium nanoparticles and superparamagnetic iron oxide nanoparticles in aluminum oxyhydroxide matrix, which is highly active and selective for epoxide hydrogenolysis at room temperature under 1 atm H 2. The catalyst was recycled for 25 times without loss of the activity.
- Kwon, Min Serk,Park, In Soo,Jang, Jum Suk,Lee, Jae Sung,Park, Jaiwook
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p. 3417 - 3419
(2008/02/12)
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- Deracemisation of aryl substituted α-hydroxy esters using Candida parapsilosis ATCC 7330: Effect of substrate structure and mechanism
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Candida parapsilosis ATCC 7330 was found to be an efficient biocatalyst for the deracemisation of aryl α-hydroxy esters (65-85% yield and 90-99% ee). A variety of aryl and aryl substituted α-hydroxy esters were synthesized to reflect steric and electronic effects on biocatalytic deracemisation. The mechanism of this biocatalytic deracemisation was found to be stereoinversion.
- Baskar,Pandian,Priya,Chadha, Anju
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p. 12296 - 12306
(2007/10/03)
-
- Recyclable Polyurea-Microencapsulated Pd(0) Nanoparticles: An Efficient Catalyst for Hydrogenolysis of Epoxides
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(Matrix presented) Pd nanoparticles (~2 nm in size) microencapsulated in polyurea is an efficient and recyclable catalyst for reductive ring-opening hydrogenolysis of epoxides, using either HCOOH/Et3N or H2 as a hydrogen donor.
- Ley, Steven V.,Mitchell, Claire,Pears, David,Ramarao, Chandrashekar,Yu, Jin-Quan,Zhou, Wuzong
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p. 4665 - 4668
(2007/10/03)
-
- Tyrosine phosphatase inhibitors
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A compound of the formula (I): wherein X1 and X2 are the same or different and each is a bond or a spacer having 1 to 20 atom(s) in the main chain; one of R1 and R2 is a cycle group having substituent(s) selected from 1) an optionally substituted carboxy-C1-6 alkoxy group and 2) an optionally substituted carboxy-C1-6 aliphatic hydrocarbon group, wherein the cycle group optionally has additional substituent(s), and the other is an optionally substituted cycle group or a hydrogen atom; and R3, R4 and R5 are the same or different and each is a hydrogen atom or a substituent, or R4 may link together with R3 or R5 to form an optionally substituted ring; provided that when R3 is a hydrogen atom, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-cyclohexylphenyl; when R3 is 4-methoxyphenyl, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-methoxyphenyl; and when R1 or R2 is a hydrogen atom, the adjacent X1 or X2 is not a C1-7 alkylene; or a salt thereof exhibits a protein tyrosine phosphatase inhibitory action and is useful as a prophylactic or therapeutic agent for diabetes or the like.
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-
- Substituted naphthyl benzofuran derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
-
This invention provides compounds which act as inhibitors of plasminogen activator inhibitor-1 (PAI-1) of the formula: wherein: R, R1, R2, and R3 are H, alkyl, cycloalkyl, —CH2-(cycloalkyl), alkanoyl, halo, hydr
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-
- Process for preparing optically active α-hydroxy acids and derivatives thereof
-
The present invention provides a process for preparing optically active α-hydroxy acids and derivatives thereof by subjecting the alkylated 1,3-dioxolanones of formula (IV) wherein R1and R2are the same or different and are each independently H or C1-6alkyl; R5is H, C1-16alkyl, or unsubstituted or substituted phenyl; and R6is C1-8alkyl, C2-7alkenyl or unsubstituted or substituted benzyl, to either alcoholysis or hydrolysis, in which the alkylated 1,3-dioxolanones are obtained by using 10-camphorsulfonamide as a chiral auxiliary.
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-
Page/Page column 18-19
(2008/06/13)
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- Dynamic kinetic resolution via dual-function catalysis of modified cinchona alkaloids: Asymmetric synthesis of α-hydroxy carboxylic acids
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A highly enantioselective catalytic transformation of racemic α-hydroxy acids to optically active α-hydroxy acids is reported. A new procedure was developed for the condensation of racemic α-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active α-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic α-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide α-hydroxy acids and esters in high optical purity and good yields. Copyright
- Tang, Liang,Deng, Li
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p. 2870 - 2871
(2007/10/03)
-
- Phenylhydrazide as an enzyme-labile protecting group in peptide synthesis
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The enzymatic cleavage of amino acid phenylhydrazides with the enzyme tyrosinase (EC 1.14.18.1) offers a new, mild, and selective method for C-terminal deprotection of peptides. The advantages of the described methodology are the very mild oxidative removal of the protecting group at room temperature and pH 7, a high chemo- and regioselectivity, and the availability of the biocatalyst. Even in oxygen-saturated solution, the oxidation of sensitive methionine residues was not observed. These features make the methodology suitable for the synthesis of sensitive peptide conjugates. Mechanistic data suggest that the hydrolysis of the oxidized adducts proceeds by a free-radical mechanism.
- Voelkert, Martin,Koul, Surrinder,Mueller, Gernot H.,Lehnig, Manfred,Waldmann, Herbert
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p. 6902 - 6910
(2007/10/03)
-
- Mild air-oxidation of 1,3-dicarbonyl compounds with cesium salts: Novel α-hydroxylation accompanied by partial hydrolysis of malonate derivatives
-
1,3-Dicarbonyl compounds (1) were efficiently oxygenated at the α-position with cesium salts, such as CsF or Cs2CO3 (0.1 Meq) in DMF at room temperature. Reaction of malonate derivatives (1a, b) with excess amount (2 Meq) of Cs2
- Watanabe, Toshiko,Ishikawa, Tsutomu
-
p. 7795 - 7798
(2007/10/03)
-
- Enantioselective synthesis of α-hydroxy acids employing (1S)-(+)-N,N-diisopropyl-10-camphorsulfonamide as chiral auxiliary
-
matrix presented I R1=H, Me, Ph II (>98 de.) III Lewis acid (BF3·-OEt2) catalyzed condensation of dimethoxy acetal 2 with α-hydroxy acids produces chiral 1,3-dioxolanones I. The enolates derived from these compounds underg
- Chang, Jia-Wen,Jang, Der-Pin,Uang, Biing-Jiun,Liao, Fen-Ling,Wang, Sue-Lein
-
p. 2061 - 2063
(2008/02/09)
-
- Oxidation of 1,3-dicarbonyl compounds using (camphorylsulfonyl)oxaziridines
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The oxidation of 1,3-dicarbonyl compounds with (camphorylsulfonyl)oxaziridines 2 was studied in both cyclic and acyclic systems. Two reaction pathways were identified: Enolate α-hydroxylation and a novel Baeyer-Villiger type oxidation. The Baeyer-Villiger oxidation product was observed only for the ketones and arises via rearrangement of an alkoxy epoxide. Synthetically useful ee's (82-95%) were observed only for enolates of β-ketoesters where the keto group is part of a 6-membered ring.
- Davis, Franklin A.,Liu, Hu,Chen, Bang-Chi,Zhou, Ping
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p. 10481 - 10492
(2007/10/03)
-
- Enantioselectivity of Pseudomonas cepacia lipase for the acetylation of 2-hydroxy carboxylic acid esters+
-
Structurally different ethyl or methyl 2-hydroxy carboxylates were resolved by Pseudomonas cepacia lipase-catalysed acetylations with vinyl acetate in diethylether. One type of the alcoholic substrates (2-hydroxy-2-arylacetates and 2-hydroxy-3-arylpropinates) contained a HO-group at the stereocentre. These compounds were resolved with high enantioselectivity (ee 91 → 99) at ca. 50% conversion. The other alcoholic substrates ((threo-2-hydroxy-3-methylbutyrate and threo- or erythro-2-hydroxy-3-aryl-3-arylthio(or aryloxy)propionates) with two stereocentres generally resulted in enantiopure products and the reactions stopped at 50 % conversion.
- Sundholm, Oskari,Kanerva, Liisa T.
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p. 625 - 640
(2007/10/03)
-
- Stereochemical control in microbial reduction. Part 31: Reduction of alkyl 2-oxo-4-arylbutyrates by baker's yeast under selected reaction conditions
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Treatment of baker's yeast with phenacyl chloride in an aqueous-organic solvent has been proven to be an effective method of inhibiting the enzymes that afford (S)-enantiomers of α-hydroxy esters in the reduction of α-keto esters. The procedure is effective for the whole-cell system to produce the (R)-product with high chemical yield and high enantiomeric excess.
- Dao, Duc Hai,Okamura, Mutsuo,Akasaka, Takeshi,Kawai, Yasushi,Hida, Kouichi,Ohno, Atsuyoshi
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p. 2725 - 2737
(2007/10/03)
-
- Asymmetric synthesis of α-hydroxy acids via β-lactams
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A diastereoselective synthesis of β-lactams 5a-e and 6a-e has been achieved, via a Staudinger reaction using imines derived from (1S)-(+)-camphor-10-sulfonamide, in good yields. The major diastereomers 6a-e were isolated in pure form by crystallization. T
- Srirajan,Deshmukh,Puranik,Bhawal
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p. 2733 - 2738
(2007/10/03)
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- A convenient and mild procedure for the preparation of hydroxyesters from lactones and hydroxyacids
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An alcoholic solution of lactones and hydroxyacids stored on Amberlyst-15 results in the formation of corresponding hydroxyesters in high yields.
- Anand,Selvapalam
-
p. 2743 - 2747
(2007/10/02)
-
- Competing O - H insertion and β-elimination in rhodium carbenoid reactions; synthesis of 2-alkoxy-3-arylpropanoates
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Rhodium(II) carboxylate catalysed decomposition of diazo esters 3 and 4 in the presence of alcohols or water results in formation of 2-alkoxy- or 2-hydroxy-3-arylpropanoates respectively by O - H insertion in competition with cinnamates by elimination; the ratio of insertion to elimination is dramatically affected by the carboxylate ligand on rhodium. Use of methanol-d as the alcohol confirms that the alkene does not arise by elimination from the initial alkoxyester product.
- Cox, Geoffrey G.,Haigh, David,Hindley, Richard M.,Miller, David J.,Moody, Christopher J.
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p. 3139 - 3142
(2007/10/02)
-
- A Novel Method for the Preparation of Acid-Sensitive Epoxides from Olefins with the Combined Use of Molecular Oxygen and Aldoacetal Catalyzed by a Cobalt(II) Complex
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An efficient synthesis of acid-sensitive epoxides, such as chromene oxide or epoxide of γ,δ-unsaturated alcohol, was successfully achieved by the oxygenation of corresponding olefins with the combined use of an atmospheric pressure of molecular oxygen and aldoacetal catalyzed by a cobalt(II) complex coordinated with the 1,3-diketone ligand.The reactions proceeded under mild and neutral conditions, and the desired epoxides were obtained in good yields.Neither overoxidation nor decomposition of the formed epoxide was observed under the present reaction conditions.Furthermore, various silyl enol ethers and silyl ketene acetals, acid-sensitive compounds, were also smoothly monooxygenated into the corresponding α-hydroxy ketones and α-hydroxy carboxylic acid esters, respectively.
- Yorozu, Kiyotaka,Takai, Toshihiro,Yamada, Tohru,Mukaiyama, Teruaki
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p. 2195 - 2202
(2007/10/02)
-
- Epoxidation of Olefinic Compounds with Combined Use of Molecular Oxygen and Propionaldehyde Diethyl Acetal Catalyzed by Cobalt(II) Complex. Efficient Method for the Preparation of Acid-sensitive Epoxides
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Synthesis of acid-sensitive epoxides such as epoxide of bishomoallyl alcohol or chromene oxide was achieved by the epoxidation of corresponding olefins with combined use of molecular oxygen and propionaldehyde diethyl acetal catalyzed by cobalt(II) comple
- Yorozu, Kiyotaka,Takai, Toshihiro,Yamada, Tohru,Mukaiyama, Teruaki
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p. 1579 - 1582
(2007/10/02)
-
- Pen G acylase catalyzed resolution of phenylacetate esters of secondary alcohols
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Penicillin G acylase from E. coli (E.C. 3.5.1.11) immobilized on Eupergit C is used for the kinetic resolution of phenyl acetate esters of secondary alcohols of pharmaceutical interest.
- Baldaro,D'Arrigo,Pedrocchi-Fantoni,Rosell,Tagliani,Terreni,Servi
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p. 1031 - 1034
(2007/10/02)
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- A New and Facile Method for the Direct Preparation of α-Hydroxycarboxylic Acid Esters from α,β-Unsaturated Carboxylic Acid Esters with Molecular Oxygen and Phenylsilane Catalyzed by Bis(dipivaloylmethanato)manganese(II) Complex
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In the presence of a catalytic amount of bis(dipivaloylmethanato)manganese(II) complex, the oxygenation of benzyl crotonate with molecular oxygen and phenylsilane proceeds smoothly under a mild condition to give benzyl 2-hydroxybutyrate in high yield.The reaction provides a new and convenient method for the direct preparation of various α-hydroxycarboxylic acid esters starting from α,β-unsaturated carboxylic acid esters.The influence of substituents of olefins on regioselectivity is also studied.
- Inoki, Satoshi,Kato, Koji,Isayama, Shigeru,Mukaiyama, Teruaki
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p. 1869 - 1872
(2007/10/02)
-
- CERTAIN ACYCLIC, ALICYCLIC, AROMATIC OR HETEROCYCLIC DERIVATIVES OF 3-BENZOYLAMINO-2-OXO- BUTYL-AMINO-CARBONYL-OXY-3-PROPANOIC ACIDS, ESTERS THEREOF, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND THEIR ENKEPHALINASE INHIBITING PROPERTIES
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Compounds of the formula STR1 wherein Y is oxygen or sulfur are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of R 1 may also be useful as analgesics due to their enkepahlinase inhibition activity.
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- ASYMMETRIC OXIDATION OF OLEFINS WITH OSMIUM TETROXIDE COORDINATED BY CHIRAL DIAMINES DERIVED FROM L-TARTARIC ACID
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The enantioselective oxidation of olefins with OsO4 coordinated by chiral diamines derived from L-tartaric acid is described.Phenylketene dimethylacetal and trans-stilbene are converted to (R)-methyl mandelate and (1R,2R)-1,2-diphenyl-1,2-ethanediol with
- Yamada, Tohru,Narasaka, Koichi
-
p. 131 - 134
(2007/10/02)
-
- Spiro Asymmetric Induction. Synthesis of Optically Pure α-Hydroxy Acid Derivatives by Alkylation of a Chiral Glycolate Enolate
-
The enolates of spiro-fused dioxolanones 4A and 4B serve as chiral glycolate enolate equivalents, providing either enantiomer of the α-substituted α-hydroxy esters 13 upon alkylation and hydrolysis
- Pearson, William H.,Cheng, Minn-Chang
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p. 3746 - 3748
(2007/10/02)
-
- Stereochemical Studies. LX. Neighboring Phenyl Group Participation. I. Stereospecific Transformation of L-Phenylalanine to Optically Active Tropic Acid
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Trifluoroacetolysis of (S)-3-phenyllactic acid ester sulfonate((S)-7), obtained from L-phenylalanine via nitrous acid deamination followed by ethanolysis, afforded (R)-tropic acid ester((R)-8) in good yield by phenyl migration with inversion, while acetol
- Juang, Tzuoh Miin,Yamada, Shun-ichi
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p. 4426 - 4430
(2007/10/02)
-