- Preparation method of (s)-3-hydroxytetrahydrofuran
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The invention provides a preparation method of (s)-3-hydroxytetrahydrofuran. According to the preparation method, ethyl 4-chloroacetoacetate is taken as an initial raw material, (s)-4-chloro-3 hydroxyl-1-butanol is prepared, wherein a substrate is dissolved in a first solvent, an alkali is added, under the catalytic effect of a first catalyst and a second catalyst, asymmetric hydrogenation reaction with hydrogen gas is carried out to produce (s)-4-chloro-3 hydroxyl-1-butanol; chiral 3-hydroxytetrahydrofuran is prepared, wherein prepared chiral 4-chloro-3 hydroxyl-1-butanol is dissolved in a second solvent, an acid is added as a catalyst, and reaction is carried out to obtain (s)-3-hydroxytetrahydrofuran; wherein the first catalyst is a complex generated through reaction of [Ir(COD)Cl]2 with phosphine-pyridine ligand, and the second catalyst is Ru-MACHO complex. The reaction route is short; technology is simple; raw materials are cheap and easily available; production cost is low; reaction process environment pollution is low; product optical purity is high; and the preparation method is suitable for industrialized production.
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Paragraph 0032; 0037-0039; 0044-0046; 0051-0053; 0058-0060
(2019/11/13)
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- A S - (+) -3 - hydroxy tetrahydrofuran chemical synthesis method
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The invention discloses a S - (+) - 3 - hydroxy tetrahydrofuran chemical synthesis method, includes the following operation steps: 1, compound 1 in the presence of thionyl chloride and methanol reaction to obtain compound 2; 2, in the solvent, compound 2 in the presence of a reducing agent and the reaction to obtain compound 3; 3, compound 3 in the presence of paratoluene sulfonic acid, reaction to obtain compound S - (+) - 3 - hydroxy tetrahydrofuran.
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Paragraph 0023-0025
(2019/04/04)
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- Preparation method of (S)-3-hydroxytetrahydrofuran
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The invention discloses a preparation method of (S)-3-hydroxytetrahydrofuran. The problems that butantriol is difficult to separate in the production process, the yield is not high and the impurity content and the isomer content of the products are high are mainly solved. The preparation method of (S)-3-hydroxytetrahydrofuran comprises the following steps: under the existence of sulfoxide chloride, malic acid reacts with methanol to generate a compound II; under the existence of silver oxide, performing reaction on the compound II and benzyl bromide to generate a compound III; reducing the compound III by sodium borohydride to generate a compound IV; performing dehydration and ring closing on the compound IV by p-toluenesulfonic acid to generate a compound V; and taking palladium carbon asa catalyst and performing hydrogen reduction treatment on the compound V to obtain the product. The method is simple in aftertreatment and environment-friendly; the yield of the products is increasedby 80 percent or more, the purity is more than 99.5 percent and the chiral purity is more than 99.2 percent; and the method is suitable for industrialized production. (The formulas are as shown in the description).
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Paragraph 0043
(2018/06/15)
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- Methodology Development in Directed Evolution: Exploring Options when Applying Triple-Code Saturation Mutagenesis
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Directed evolution of stereo- or regioselective enzymes as catalysts in asymmetric transformations is of particular interest in organic synthesis. Upon evolving these biocatalysts, screening is the bottleneck. To beat the numbers problem most effectively, methods and strategies for building “small but smart” mutant libraries have been developed. Herein, we compared two different strategies regarding the application of triple-code saturation mutagenesis (TCSM) at multiresidue sites of the Thermoanaerobacter brockii alcohol dehydrogenase by using distinct reduced amino-acid alphabets. By using the synthetically difficult-to-reduce prochiral ketone tetrahydrofuran-3-one as a substrate, highly R- and S-selective variants were obtained (92–99 % ee) with minimal screening. The origin of stereoselectivity was provided by molecular dynamics analyses, which is discussed in terms of the Bürgi–Dunitz trajectory.
- Qu, Ge,Lonsdale, Richard,Yao, Peiyuan,Li, Guangyue,Liu, Beibei,Reetz, Manfred T.,Sun, Zhoutong
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p. 239 - 246
(2018/02/09)
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- Production technology of 3-hydroxytetrahydrofuran with high optical purity
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The invention discloses a production technology of3-hydroxytetrahydrofuran with high optical purity. The production technology comprises the following steps: (1) taking chloroacetoacetic acid ethyl ester as a starting raw material, adding appropriate amount of solvents, chiral catalysts and reducing agents, and reacting at an appropriate temperature to obtain chiral ethyl 4-chloro-3-hydroxybutyrate; (2) taking the chiral ethyl 4-chloro-3-hydroxybutyrate obtained in step (1) as a raw material, adding the appropriate amount of solvents and metal borohydride reducing agents, and reacting at the appropriate temperature to obtain chiral 4-chloro-3-hydroxy-1-butanol; (3) taking the chiral 4-chloro-3-hydroxy-1-butanol obtained in step (2) as the raw material, adding appropriate amount of catalysts and solvents, and reacting at the appropriate temperature to obtain chiral 3-hydroxytetrahydrofuran. According to the production technology of the 3-hydroxytetrahydrofuran with the high optical purity, the chiral 3-hydroxytetrahydrofuran can be produced through a three-step reaction, the shortcomings of complicated production operation and high production cost are solved, and products with high optical purity can be produced.
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Paragraph 0028; 0032; 0037; 0038; 0043
(2017/10/06)
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- A pharmaceutical intermediates (S)-3 - hydroxy tetrahydrofuran preparation method (by machine translation)
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The invention provides a pharmaceutical intermediate (S)- 3 - hydroxy tetrahydrofuran preparation method. The method other than racemic 1, 2, 4 - butanetriol as raw materials synthesis of racemic 3 - hydroxy tetrahydrofuran, then esterification of racemic tetrahydrofuran-yl - 3 - fatty acid ester. By lipase hydrolysis in the racemic mixture of (R)- tetrahydrofuran-based - 3 - fatty acid ester after, in in the hydrolysis product under the condition of separating, using the mitsunobu reaction will be hydrolyzed to obtain the of (R)- 3 - hydroxy tetrahydrofuran is converted into (S)- tetrahydrofuran-based - 3 - carboxylic acid ester, finally under alkaline condition all of the tetrahydrofuran ester hydrolyzed to obtain the final product (S)- 3 - hydroxy tetrahydrofuran. (by machine translation)
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Paragraph 0043
(2017/08/31)
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- (S)- 3 - hydroxy tetrahydrofuran and (R)- 3 - hydroxy tetrahydrofuran preparation method
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The invention discloses a preparation method of (S)-3-hydroxytetrahydrofuran and (R)-3-hydroxytetrahydrofuran, relating to the technical field of preparation of five-element heterocyclic compounds containing one oxygen atom as the only heterocyclic atom. The method comprises the following steps: by using (S)-carnitine or (R)-carnitine as the initial raw material, carrying out reduction reaction in a reducer and an organic solvent to obtain (S) or (R)-2,4-dihydroxy-N,N,N-trimethyl butyl amine alkali; adding a hydrogen chloride organic solvent solution into an organic solvent to perform salification reaction to obtain (S) or (R)-2,4-dihydroxy-N,N,N-trimethyl butyl amine hydrochloride; and finally, adding alkali into a polar solvent, heating, and carrying out cyclization reaction to obtain the (S) or (R)-3-hydroxytetrahydrofuran. The method has the advantages of low cost, simple technique, high yield, cheap and accessible raw materials, short reaction steps, short period and low pollution, and is suitable for industrial production.
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Paragraph 0050; 0051; 0052
(2017/08/02)
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- Preparation Method for 3-Hydroxytetrahydrofuran
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The present invention relates to a method for preparing 3-hydroxytetrahydrofuran, and more specifically, to a method for preparing 3-hydroxytetrahydrofuran (3) from 4-halo-3-hydroxybutyric acid ester by means of Reaction Formula 1 below, wherein the method comprises the steps of: reacting 4-halo-1,3-butanediol with an inorganic base in C1-C4 alcohol; and then refining 3-hydroxytetrahydrofuran (3) by removing filtering and removing generated salt and performing vacuum distillation thereonto. [Reaction Formula 1] Wherein X=Cl, Br or I, and R=C1-C4 alkyl group or aryl group.
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Paragraph 0021; 0024; 0027; 0028
(2017/08/02)
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- Catalytic Asymmetric Reduction of Difficult-to-Reduce Ketones: Triple-Code Saturation Mutagenesis of an Alcohol Dehydrogenase
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Catalytic asymmetric reduction of prochiral ketones with the formation of enantio-pure secondary alcohols is of fundamental importance in organic chemistry, chiral man-made transition-metal catalysts, or organocatalysts and enzymes of the alcohol dehydrogenase (ADH) type. A distinct limitation is the traditional requirement that the α- and α′-moieties flanking the carbonyl function differ sterically and/or electronically. Difficult-to-reduce ketones such as tetrahydrofuran-3-one and tetrahydrothiofuran-3-one and related substrates are particularly challenging, irrespective of the catalyst type. The ADH from Thermoethanolicus brockii (TbSADH) is an attractive industrial biocatalyst, because of its high thermostability, but it also fails in the reduction of such ketones. We have successfully applied directed evolution using the previously developed concept of triple-code saturation mutagenesis at sites lining the TbSADH binding pocket with tetrahydrofuran-3-one serving as the model compound. Highly (R)- and (S)-selective variants were evolved (95%-99% ee) with minimal screening. These robust catalysts also proved to be effective in the asymmetric reduction of tetrahydrothiofuran-3-one and other challenging prochiral ketones as well. The chiral products, which are generally prepared by multistep routes, serve as synthons in the preparation of several important therapeutic drugs.
- Sun, Zhoutong,Lonsdale, Richard,Ilie, Adriana,Li, Guangyue,Zhou, Jiahai,Reetz, Manfred T.
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p. 1598 - 1605
(2016/03/15)
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- Use of 'small but smart' libraries to enhance the enantioselectivity of an esterase from Bacillus stearothermophilus towards tetrahydrofuran-3-yl acetate
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Two libraries of simultaneous double mutations in the active site region of an esterase from Bacillus stearothermophilus were constructed to improve the enantioselectivity in the hydrolysis of tetrahydrofuran-3-yl acetate. As screening of large mutant libraries is hampered by the necessity for GC/MS analysis, mutant libraries were designed according to a 'small but smart' concept. The design of focused libraries was based on data derived from a structural alignment of 3317 amino acid sequences of α/β-hydrolase fold enzymes with the bioinformatic tool 3dm. In this way, the number of mutants to be screened was substantially reduced as compared with a standard site-saturation mutagenesis approach. Whereas the wild-type esterase showed only poor enantioselectivity (E = 4.3) in the hydrolysis of (S)-tetrahydrofuran-3-yl acetate, the best variants obtained with this approach showed increased E-values of up to 10.4. Furthermore, some variants with inverted enantiopreference were found. A semi-rational approach was applied for the enhancement of the enantioselectivity of an esterase from Bacillus stearothermophilus towards the industrially interesting substrate tetrahydrofuran-3-yl acetate, based on data derived from structural alignment. The design of 'small but smart' libraries led to a 2.4-fold increase of (S)-selectivity compared to wild type enzyme, while some mutants with marginal (R)-selectivity were found.
- Nobili, Alberto,Gall, Markus G.,Pavlidis, Ioannis V.,Thompson, Mark L.,Schmidt, Marlen,Bornscheuer, Uwe T.
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p. 3084 - 3093
(2013/07/26)
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- Mitsunobu reaction with 4-(diphenylphosphino)benzoic acid: A separation-friendly bifunctional reagent that serves as both a reductant and a pronucleophile
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4-(Diphenylphosphino)benzoic acid was used for the Mitsunobu reaction as a bifunctional reagent that served as both a reductant and a pronucleophile. When combined with di-2-meth-oxyethyl azodicarboxylate, inversion of a secondary alcohol stereospecifically occurred to give an ester carrying a phosphine oxide group. The reaction mixture was directly hydrolyzed to give an inverted secondary alcohol in sufficient stereo and chemical purities by the presently developed chromatography-free process in conjunction with basic extraction, drying, and concentration. Georg Thieme Verlag Stuttgart - New York.
- Muramoto, Natsuko,Yoshino, Kazuki,Misaki, Tomonori,Sugimura, Takashi
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p. 931 - 935
(2013/05/21)
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- Enantioselective synthesis of HIV protease inhibitor amprenavir via Co-catalyzed HKR of 2-(1-azido-2-phenylethyl)oxirane
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A short and efficient enantioselective synthesis of the HIV protease inhibitor amprenavir 1 (99% ee) as well as a formal synthesis of saquinavir 3 have been achieved in high enantiomeric purity starting from commercially available materials. Our strategy mainly comprises a Co-catalyzed two-stereocentred hydrolytic kinetic resolution (HKR) of racemic 2-(1-azido-2-phenylethyl)oxirane as the chirality inducing step. Also presented is a concise synthesis of (S)-3-hydroxytetrahydrofuran 4, the key structural feature, in high enantiomeric purity (98% ee).
- Gadakh, Sunita K.,Santhosh Reddy,Sudalai, Arumugam
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experimental part
p. 898 - 903
(2012/09/22)
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- A novel lipase enzyme panel exhibiting superior activity and selectivity over lipase B from Candida antarctica for the kinetic resolution of secondary alcohols
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A novel, commercially available lipase enzyme panel performing kinetic bioresolutions of a number of secondary alcohols is reported. The secondary alcohols that have been chosen are known from the literature to be particularly challenging substrates to resolve. Following initial screening, four co-solvents were investigated for each lead enzyme in an effort to assess their tolerance to common organic solvents. The superiority of these novel enzymes over lipase B from Candida antarctica (CALB) has been demonstrated.
- O'Neill, Maeve,Beecher, Denis,Mangan, David,Rowan, Andrew S.,Monte, Agnieszka,Sroka, Stefan,Modregger, Jan,Hundle, Bhupinder,Moody, Thomas S.
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experimental part
p. 583 - 586
(2012/08/13)
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- PROCESS FOR THE EFFICIENT PREPARATION OF 3-HYDROXYTETRAHYDROFURAN
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Disclosed is a process for the efficient preparation of 3-hydroxytetrahydrofuran. In particular, the present invention provides a process for the preparation of 3-hydroxytetrahydrofuran by performing cyclization of 4-halo-1,3-butanediol either neat or in an organic solvent by heating to 75°C to 18O°C. In the present invention, acidic solution is not used in the cyclization and, thus, the reaction environment is improved. Further, the cyclization product 3-hydroxytetrahydrofuran is purified by a simple process. In addition, according to the present invention, chirality of the starting material is substantially maintained. Consequently, chiral 3-hydroxytetrahydrofuran with a high optical purity of 99.0% ee or better can be prepared economically, in high yield.
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Paragraph 81-82
(2008/12/07)
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- Synthesis of a variety of optically active hydroxylated heterocyclic compounds using epoxide hydrolase technology
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Novel epoxide hydrolases in Yarrowia lipolytica have been shown to hydrolyse a variety of functionalised epoxides with good to excellent stereoselectivity and at high volumetric productivities. Individual biotransformation products have been converted into optically active (R)-(tetrahydrofuran-2-yl)methanol (6), (S)-N-benzyl-3-hydroxypyrrolidine (7), (S)-3-hydroxytetrahydrothiophene (8), (S)-N-benzyl-3-acetoxypiperidine (10), (S)-3-hydroxytetrahydrofuran (16) and (R)-[(S)-N-benzylpyrrolidin-2-yl](phenyl)methanol (20).
- Pienaar, Daniel P.,Mitra, Robin K.,Deventer, Thomas I. van,Botes, Adriana L.
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body text
p. 6752 - 6755
(2009/04/06)
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- METHOD FOR PREPARING 3-HYDROXYTETRAHYDROFURAN USING CYCLODEHYDRATION
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Disclosed is a method of preparing 3-hydroxytetrahydrofuran using cyclodehydration. More particularly, this invention relates to a method of preparing 3-hydroxytetrahydrofuran, including subjecting 1,2,4-butanetriol to cyclodehydration under reaction conditions of a reaction temperature of 30~180°C and reaction pressure of 5000 psig or less in the presence of a strong acid cation exchange resin catalyst having a sulfonic acid group as an exchange group. According to the method of this invention, 3-hydroxytetrahydrofuran can be economically prepared at higher yield and productivity than when using conventional methods.
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Page/Page column 5
(2008/06/13)
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- New approaches to the industrial synthesis of HIV protease inhibitors
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Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a novel and economical method for the preparation of a key intermediate, (3S)-hydroxytetrahydrofuran, from L-malic acid. Three new approaches to the assembly of Amprenavir are also discussed. Of these, a synthetic route in which an (S)-tetrahydrofuranyloxy carbonyl is attached to L-phenylalanine appears to be the most promising manufacturing process, in that it offers satisfactory stereoselectivity in fewer steps.
- Honda, Yutaka,Katayama, Satoshi,Kojima, Mitsuhiko,Suzuki, Takayuki,Kishibata, Naomi,Izawa, Kunisuke
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p. 2061 - 2070
(2007/10/03)
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- Process for the preparation of 3-hydroxytetrahydrofuran
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An industrial advantage process for producing high-purity 3-hydroxytetrahydrofuran easily and simply, which comprises reducing a 4-halo-3-hydroxybutyric acid ester (1) with a boron hydride compound and/or an aluminum hydride compound as a reducing agent in an organic solvent immiscible with water; treating the reaction mixture with an acid and water to thereby effect conversion to the corresponding 4-halo-1,3-butanediol and at the same time giving an aqueous solution containing said compound; carrying out the cyclization reaction of the 4-halo-1,3-butanediol in said aqueous solution; extracting the resulting 3-hydroxytetrahydrofuran from the 3-hydroxytetrahydrofuran-containing aqueous solution using an organic solvent immiscible with water; and isolating the 3-hydroxytetrahydrofuran by concentration and/or distillation of the solution obtained.
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Page column 13, 14-15
(2008/06/13)
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- A high-throughput-screening method for the identification of active and enantioselective hydrolases
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A rapid and reliable test for the determination of hydrolase activity and enantioselectivity comprises the conversion of acetic acid released from acetates to NADH by using a commercially available enzymatic test-kit (see scheme). The NAHDH is spectrophotometrically quantified in a microtiter plate format.
- Baumann, Markus,Stuermer, Rainer,Bornscheuer, Uwe T.
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p. 4201 - 4204
(2007/10/03)
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- Rapid screening of hydrolases for the enantioselective conversion of 'difficult-to-resolve' substrates
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Hydrolases showing high enantioselectivity towards three racemic alcohols (1-methoxy-2-propanol, 3-hydroxy-tetrahydrofuran, 3-butyn-2-ol) and pantolactone were identified by a step-wise screening procedure. Initially, those biocatalysts, which exhibited hydrolytic activity towards the corresponding acetates or butyrates, were selected out of >100 enzymes. Here, rapid screening was performed in a pH-indicator-based format in microtiter plates. Subsequently, enantioselectivity of active hydrolases was determined in small scale reactions (~1 mg substrate per reaction) by means of gas chromatography using chiral columns. Enzymes exhibiting highest enantioselectivities were then chosen for preparative scale resolution. Using this strategy, at least one suitable hydrolase was found for 3 out of the 4 model compounds examined, allowing efficient kinetic resolution. Moreover, in all cases enantiocomplementary enzymes were identified thus enabling access to both enantiomers of all substrates.
- Baumann, Markus,Hauer, Bernhard H.,Bornscheuer, Uwe T.
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p. 4781 - 4790
(2007/10/03)
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- Process for preparing optically active cyclic compounds
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A process for preparing optically active 3-hydroxy-γ-butyrolactone or optically active 3-hydroxytetrahydrofuran through a short route and by using an easily available and inexpensive starting material and an inexpensive reagent easy to handle is disclosed. The process comprises cyclizing an optically active compound represented by formula (II): STR1 wherein Q represents an alkoxycarbonyl group having 1 to 4 carbon atoms or a hydroxymethyl group; X represents a halogen atom; and the asterisk * means an asymmetric carbon atom, under an acidic condition.
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- Practical syntheses of (S)-4-hydroxytetrahydrofuran-2-one, (S)-3-hydroxytetrahydrofuran and their (R)-enantiomers
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Optically active 4-hydroxytetrahydrofuran-2-one (3) has been synthesized in good yield from optically active ethyl 4-chloro-3-hydroxybutanoate (2) by refluxing with dilute hydrochloric acid. In a similar manner, optically active 3-hydroxytetrahydrofuran (5) was prepared from optically active 4-chloro-1,3-butanediol (4), which was derived from 2 by NaBH4 reduction. These new cyclizations proceed without racemization. VCH Verlagsgesellschaft mbH, 1997.
- Yuasa, Yoshifumi,Tsuruta, Haruki
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p. 1877 - 1879
(2007/10/03)
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- Lewis Acid-Catalyzed Deprotection of p-Methoxybenzyl Ether
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The p-methoxybenzyl protecting group was readily removed from alcohols and phenols using catalytic amounts of AlCl3 or SnCl2 · 2H2O in the presence of EtSH at room temperature. Under these mild conditions other protecting groups such as methyl and benzyl ethers, p-nitrobenzoyl esters, TBDPS ethers and isopropylidene acetal were unchanged.
- Bouzide, Abderrahim,Sauvé, Gilles
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p. 1153 - 1154
(2007/10/03)
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- AROMATIC AMIDINE DERIVATIVES AND SALTS THEREOF
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An anticoagulant agent which comprises, as an active ingredient, an aromatic amidine derivative represented by the following general formula (1) or a salt thereof: STR1 wherein the group represented by STR2 is a group selected from indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, naphthyl, tetrahydronaphthyl and indanyl; X is a single bond, an oxygen atom, a sulfur atom or a carbonyl group; and Y is a saturated or unsaturated 5-or 6-membered heterocyclic moiety or cyclic hydrocarbon moiety optionally having a substituent group, an amino group optionally having a substituent group or an aminoalkyl group optionally having a substituent group.The inventive compound has a high anticoagulant capacity based on its excellent FXa inhibition activity.
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- Asymmetric hydrosilylation of dihydrofurans by use of palladium-MOP catalyst
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Catalytic asymmetric hydrosilylation of dihydrofuran derivatives including 7-oxabicyclo[2.2.1]heptenes with trichlorosilane proceeded in the presence of 0.1 mol % of palladium catalyst bearing (R)-2-methoxy-2'-diphenyl-phosphino-1,1'-binaphthyl ((R)-MOP) to give the corresponding hydrosilylation products of up to 95% ee. A regio-selective opening of the bicyclic system gave a highly functionalized cyclohexane in an optically active form.
- Uozumi,Hayashi
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p. 2335 - 2338
(2007/10/02)
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- CHIRAL SYNTHESIS VIA ORGANOBORANES. 19. THE SUCCESSFUL ONE-CARBON HOMOLOGATION OF HETEROCYCLIC BORONATE ESTERS WITH HIGH OPTICAL PURITY
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An exploratory study was undertaken to establish the applicability of the one-carbon homologation to heterocyclic boronic esters.This procedure involves the use of (cloromethyl)lithium, LiCH2Cl, generated in situ by the reaction of bromochloromethane and n-BuLi in THF at -78 deg C in the presence of an enantiomerically pure heterocyclic boronic ester.These heterocyclic boronic esters were prepared via asymmetric hydroboration of representative heterocyclic olefins bearing either an endocyclic or exocyclic double bond with either Ipc2BH or IpcBH2 in THF.
- Brown, Herbert C.,Gupta, Ashok K.,Rangaishenvi, Milind V.,Vara Prasad, J. V. N.
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p. 283 - 294
(2007/10/02)
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- Chiral Synthesis via Organoboranes. 6. Hydroboration. 74. Asymmetric Hydroboration of Representative Heterocyclic Olefins with Diisopinocamphenylborane. Synthesis of Heterocyclic Boronates and Heterocyclic Alcohols of Very High Enantiomeric Purity
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The hydroboration of representative heterocycles bearing an endocyclic double bond with diisopinocamphenylborane (Ipc2BH) was investigated systematically to establish the asymmetric induction achieved in the reaction.The hydroboration of 2,3- and 2,5-dihydrofurans, 1,4-epoxy-1,4-dihydronaphthalene, and 2,3-dihydrothiophene with Ipc2BH in THF at -25 deg C proceeded very cleanly to afford the corresponding trialkylboranes.These trialkylboranes readily eliminate α-piene on treatment with acetaldehyde to give the corresponding boronates, R*B(OR)2.Oxidation afforded in high yields the corresponding heterocyclic alcohols of 100percent ee.N-(Carbobenzyloxy)-3-pyrroline could not be hydroborated with Ipc2BH below 0 deg C.The oxidation of the intermediate trialkylborane gave N-(carbobenzyloxy)-3-pyrrolidinol in 89percent ee.Similarly, six-membered heterocyclic olefins, namely, 3,4-dihydropyran and 3,4-dihydrothiapyran, were hydroborated with Ipc2BH at 0 deg C in THF.The resulting trialkylboranes on treatment with acetaldehyde followed by oxidation yielded 3-hydroxytetrahydropyran and 3-hydroxytetrahydrothiapyran of 83percent and 66percent ee, respectively.N-(Carbobenzyloxy)-1,2,3,6-tetrahydropyridine, hydroborated with Ipc2BH at 0 deg C, followed by oxidation, afforded the corresponding 3- and 4-piperidinols in an 85:15 ratio.The asymmetric induction achieved during hydroboration was 70percent.The five-membered heterocyclic boronates of very high optical purity, highly versatile synthetic intermediates, were isolated both as the diethyl and the diethanolamine esters.
- Brown, Herbert C.,Prasad, J. V. N. Vara
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p. 2049 - 2054
(2007/10/02)
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