- Introduction of Hindered Electrophiles via C-H Functionalization in a Palladium-Catalyzed Multicomponent Domino Reaction
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A general method for the incorporation of secondary alkyl iodides in a palladium-catalyzed multicomponent domino reaction is reported. With the relatively inexpensive Pd(OAc)2 as the catalyst and norbornene as a mediator, a variety of 1,2,3-trisubstituted aromatic compounds were synthesized. The reaction was shown to be scalable, producing excellent isolated yields on up to 5 mmol scale. Chiral alkyl iodides were also incorporated without any loss of stereochemical information. The developed method offers an expedient and mild C-H functionalization strategy for the synthesis of sterically congested aromatic compounds in a one-pot process.
- Qureshi, Zafar,Schlundt, Waldemar,Lautens, Mark
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Read Online
- Chiral tetradentate ligand, chiral ruthenium complex and method for preparing (R)-(-)-1, 3-butanediol
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The invention discloses a chiral tetradentate ligand, a chiral ruthenium complex and a method for preparing (R)-(-)-1, 3-butanediol. The structural formula of the ligand is preferred, and R1 and R2 are H, Br, tert-butyl, phenyl, 3, 5-trifluoromethyl phenyl which are independent of each other. The method overcomes the defects of high cost, large catalyst dosage, difficulty in product separation andthe like in the existing technology for preparing (R)-(-)-1, 3-butanediol, and can perform asymmetric hydrogenation on carbonyl of the substrate methyl acetoacetate and reduce the ester group to obtain (R)-(-)-1, 3-butanediol by using a low-cost and small-dosage catalyst. The reaction operation process is simple, the catalyst is simple to prepare, and the yield and ee value of the target productare 98% or above. Meanwhile, the catalyst can be used for five times, so that the cost is greatly reduced, and the potential of industrial application is achieved.
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Paragraph 0088-0089
(2021/03/24)
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- SYNTHESIS OF 3-HYDROXYBUTYRYL 3-HYDROXYBUTYRATE AND RELATED COMPOUNDS
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In various embodiments methods of preparing hydroxybutyryl 3-hydroxybutyrate and related compounds are provided along with methods of use thereof.
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Paragraph 0308; 0317; 0325-0327
(2021/04/02)
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- Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase: Sm ADH2 via an environmentally friendly TBCR system
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Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified from Stenotrophomonas maltophilia by traditional genome mining technology. The gene was cloned into Escherichia coli cells and then expressed to yield SmADH2. SmADH2 has a broad substrate spectrum and exhibits excellent tolerance and superb activity to 2-propanol even at 10.5 M (80%, v/v) concentration. Moreover, a new thermostatic bubble column reactor (TBCR) system is successfully designed to alleviate the inhibition of the by-product acetone by gas flow and continuously supplement 2-propanol. The organic waste can be simultaneously recovered for the purpose of green synthesis. In the sustainable system, structurally diverse chiral alcohols are synthesised at a high substrate loading (>150 g L-1) without adding external coenzymes. Among these, about 780 g L-1 (6 M) ethyl acetoacetate is completely converted into ethyl (R)-3-hydroxybutyrate in only 2.5 h with 99.9% ee and 7488 g L-1 d-1 space-time yield. Molecular dynamics simulation results shed light on the high catalytic activity toward the substrate. Therefore, the high 2-propanol tolerance SmADH2 with the TBCR system proves to be a potent biocatalytic strategy for the synthesis of chiral alcohols on an industrial scale.
- Yang, Zeyu,Fu, Hengwei,Ye, Wenjie,Xie, Youyu,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi
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- Rational engineering of 2-deoxyribose-5-phosphate aldolases for the biosynthesis of (R)-1,3-butanediol
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Carbon– carbon bond formation is one of the most important reactions in biocatalysis and organic chemistry. In nature, aldolases catalyze the reversible stereoselective aldol addition between two carbonyl compounds, making them attractive catalysts for the synthesis of various chemicals. In this work, we identified several 2-deoxyribose-5-phosphate aldolases (DERAs) having acetaldehyde condensation activity, which can be used for the biosynthesis of (R)-1,3-butanediol (1,3BDO) in combination with aldo-keto reductases (AKRs). Enzymatic screening of 20 purified DERAs revealed the presence of significant acetaldehyde condensation activity in 12 of the enzymes, with the highest activities in BH1352 from Bacillus halodurans, TM1559 from Thermotoga maritima, and DeoC from Escherichia coli. The crystal structures of BH1352 and TM1559 at 1.40 –2.50 ? resolution are the first full-length DERA structures revealing the presence of the C-terminal Tyr (Tyr224 in BH1352). The results from structure-based site-directed mutagenesis of BH1352 indicated a key role for the catalytic Lys155 and other active-site residues in the 2-deoxyribose-5-phosphate cleavage and acetaldehyde condensation reactions. These experiments also revealed a 2.5-fold increase in acetaldehyde transformation to 1,3BDO (in combination with AKR) in the BH1352 F160Y and F160Y/M173I variants. The replacement of the WT BH1352 by the F160Y or F160Y/M173I variants in E. coli cells expressing the DERA + AKR pathway increased the production of 1,3BDO from glucose five and six times, respectively. Thus, our work provides detailed insights into the molecular mechanisms of substrate selectivity and activity of DERAs and identifies two DERA variants with enhanced activity for in vitro and in vivo 1,3BDO biosynthesis.
- Kim, Taeho,Stogios, Peter J.,Khusnutdinova, Anna N.,Nemr, Kayla,Skarina, Tatiana,Flick, Robert,Joo, Jeong Chan,Mahadevan, Radhakrishnan,Savchenko, Alexei,Yakunin, Alexander F.
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p. 597 - 609
(2020/01/21)
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- Conformational Dynamics-Guided Loop Engineering of an Alcohol Dehydrogenase: Capture, Turnover and Enantioselective Transformation of Difficult-to-Reduce Ketones
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Directed evolution of enzymes for the asymmetric reduction of prochiral ketones to produce enantio-pure secondary alcohols is particularly attractive in organic synthesis. Loops located at the active pocket of enzymes often participate in conformational changes required to fine-tune residues for substrate binding and catalysis. It is therefore of great interest to control the substrate specificity and stereochemistry of enzymatic reactions by manipulating the conformational dynamics. Herein, a secondary alcohol dehydrogenase was chosen to enantioselectively catalyze the transformation of difficult-to-reduce bulky ketones, which are not accepted by the wildtype enzyme. Guided by previous work and particularly by structural analysis and molecular dynamics (MD) simulations, two key residues alanine 85 (A85) and isoleucine 86 (I86) situated at the binding pocket were thought to increase the fluctuation of a loop region, thereby yielding a larger volume of the binding pocket to accommodate bulky substrates. Subsequently, site-directed saturation mutagenesis was performed at the two sites. The best mutant, where residue alanine 85 was mutated to glycine and isoleucine 86 to leucine (A85G/I86L), can efficiently reduce bulky ketones to the corresponding pharmaceutically interesting alcohols with high enantioselectivities (~99% ee). Taken together, this study demonstrates that introducing appropriate mutations at key residues can induce a higher flexibility of the active site loop, resulting in the improvement of substrate specificity and enantioselectivity. (Figure presented.).
- Liu, Beibei,Qu, Ge,Li, Jun-Kuan,Fan, Wenchao,Ma, Jun-An,Xu, Yan,Nie, Yao,Sun, Zhoutong
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p. 3182 - 3190
(2019/05/15)
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- Enantioselective hydrogenation of ketones over a tartaric acid-modified raney nickel catalyst: Substrate-modifier interaction strength and enantioselectivity
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Chiral (R,R)-tartaric acid and NaBr-doubly modified Raney nickel (TA-MRNi) is a promising heterogeneous catalyst for enantioselective hydrogenation of prochiral β-keto esters. To obtain deeper insights into the factors ruling the enantioselectivity, enantiodifferentiating hydrogenation of substituted ketones was studied over TA-MRNi and NaBr-modified RNi by use of combined individual-competitive hydrogenation techniques. Relative equilibrium adsorption constants of the substrates were estimated to evaluate their relative interaction strength with adsorbed tartaric acid moiety. DFT calculations were also performed to estimate the interaction energy through hydrogen bonding, providing clear support to the kinetic analysis and surface model. It is concluded with the enantioselective hydrogenation of ketones over TA-MRNi that the enantioselectivity increases as the substrate-modifier interaction strength increases: Methyl acetoacetate (MAA) > acetylacetone (AA) ~ 4-hydroxy-2-butanone (HB) > 2-octanone (2O).
- Choliq, Azka Azkiya,Murakami, Eitaro,Yamamoto, Shota,Misaki, Tomonori,Fujita, Morifumi,Okamoto, Yasuaki,Sugimura, Takashi
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p. 1325 - 1332
(2018/09/21)
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- Efficient synthesis of the ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer
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The ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer were prepared in a short, operationally simple synthetic sequence from racemic β-butyrolactone. Enantioselective hydrolysis of β-butyrolactone with immobilized Candida antarctica lipase-B (CAL-B) results in (R)-β-butyrolactone and (S)-β-hydroxybutyric acid, which are easily converted to (R) or (S)-ethyl-3-hydroxybutyrate and reduced to (R) or (S)-1,3 butanediol. Either enantiomer of ethyl-3-hydroxybutyrate and 1,3 butanediol are then coupled, again using CAL-B, to produce the ketone body ester product. This is an efficient, scalable, atom-economic, chromatography-free, and low cost synthetic method to produce the ketone body esters.
- Budin, Noah,Higgins, Erin,DiBernardo, Anthony,Raab, Cassidy,Li, Chun,Ulrich, Scott
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p. 560 - 564
(2018/07/25)
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- Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB
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The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product.
- Gross, Johannes,Faber, Kurt,Hall, Mélanie,Prokop, Zbyněk,Janssen, Dick
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p. 1437 - 1441
(2016/12/24)
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- METHOD FOR PRODUCING 3-BUTENE-2-OL
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PROBLEM TO BE SOLVED: To provide a method for efficiently producing racemic 3-butene-2-ol having an (S)- or (R)-configuration. SOLUTION: There is provided a method for producing racemic 3-butene-2-ol, wherein an ammonium salt compound represented by the following general formula (1) (wherein, R1, R2 or R3 represents an alkyl group, an aryl group or an aralkyl group; X- represents OH-, HCO3-, CO32-, R4O-, R5CO2-, R6SO3- (R4, R5 or R6 represents an alkyl group, an aryl group or an aralkyl group) and a halide ion; n represents 0.5 when X- is CO32- and n represents 1 when X- is other than CO32-; the carbon atom marked with * is an asymmetric carbon atom) is subjected to Hofmann elimination. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0030
(2016/11/07)
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- PROCESS FOR PRODUCING (R)-3-HYDROXYBUTYL (R)-3-HYDROXYBUTYRATE
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A process for the production of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate comprising: i) contacting poly-(R)-3-hydroxybutyrate with an alcohol to transesterify the poly-(R)-3-hydroxybutyrate under transesterification conditions to produce an ester of (R)-3-hydroxybutyrate and the alcohol; ii) separating the product of step i) into a first and second portion and reducing the first portion of the (R) 3-hydroxybutyrate ester to form (R)-1,3-butanediol; and iii) contacting under transesterification conditions the (R)-1,3-butanediol from step ii) with the second portion of the transesterified ester to produce (R)-3-hydroxybutyl-(R)-hydroxybutanoate.
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Page/Page column 7
(2014/09/29)
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- A stereoselective total synthesis of decarestrictine I
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A convergent and stereoselective total synthesis of decarestrictine I, a polyketide natural product, is described. Both acid and alcohol fragments were prepared from the readily available L-malic acid via Still-Gennari olefination and Sharpless asymmetric epoxidation. The Steglich esterification and ring-closing metathesis (RCM) are employed to combine both acid and alcohol fragments. Copyright
- Yadav, Jhillu Singh,Venkatesh, Miriyal,Kumar, Alleni Suman,Reddy, Poli Adi Narayana,Reddy, Basi V. Subba,Prasad, Attaluri R.
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p. 830 - 838
(2014/07/07)
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- Stereoselective synthesis of ophiocerin B
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A stereoselective total synthesis of ophiocerin B is reported by asymmetric synthesis, starting from L-malic acid. Of the three stereogenic centers, the vic-diols C-3, C-4 were obtained by Sharpless asymmetric dihydroxylation. ARKAT-USA, Inc.
- Akkala, Bhasker,Damera, Krishna
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p. 164 - 170
(2013/09/12)
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- Asymmetric syntheses of the sex pheromones of pine sawflies, their homologs and stereoisomers
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We describe efficient and flexible enantioselective syntheses of the active enantiomers of the pheromones of pine sawflies, including the species Diprion jingyuanensis, their homologs and, stereoisomers, as well as those identified from the Chinese species Diprion jingyuanensis, i.e., 126. A total of 48 compounds, including acetates 78-101 and propanoates 102-125, have been synthesized. Our general approach towards these compounds originated from the commercially available chirons diethyl (S)- and (R)-malates, as well as ethyl (R)-3-hydroxybutanoate. The Seebach asymmetric methylation was employed in a key step to control additional configuration. Copyright
- Zheng, Jian-Feng,Lan, Hong-Qiao,Yang, Rui-Feng,Peng, Qi-Long,Xiao, Zhen-Hua,Tuo, Shi-Chuan,Hu, Kong-Zhen,Xiang, Yong-Gang,Wei, Zhen,Huang, Pei-Qiang,Zhang, Zhen
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p. 1799 - 1808,10
(2012/12/12)
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- Total synthesis of macrosphelide M from diacetone glucose
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The total synthesis of macrosphelide M is described. The key steps include the preparation of the acid and alcohol fragments from diacetone glucose and (S)-malic acid, respectively, followed by Yamaguchi esterification and macrocyclization of the tris-olefin by ring-closing metathesis. Finally, one-pot deprotection of the PMB and TBS groups with TiCl4 results in the target. The C-3/C-4 stereocenters of diacetone glucose are used for the introduction of four stereocenters, whereas the fifth stereocenter is realized from (S)-malic acid. The total synthesis of macrosphelide M was achieved from diacetone glucose and (S)-malic acid. The key steps include Yamaguchi esterification and macrocyclization of the tris-olefin by the second-generation Grubbs catalyst.
- Sharma, Gangavaram V. M.,Reddy, Post Sai
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experimental part
p. 2414 - 2421
(2012/05/20)
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- Synthesis and evaluation of a broad range of new chiral phosphine-carbene ligands for asymmetric hydrogenation
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A straightforward and gram scale synthesis (six-step synthesis from enantioenriched β-hydroxy esters) of new structurally simple phosphine-carbene ligands bearing a single stereogenic centre has been achieved. Enantioselectivities of up to 60-63% could be achieved in the hydrogenation of methylstilbene and dehydroaminoacids when the reactions were performed under 20-50 bar hydrogen pressure.
- Passays, Johan,Ayad, Tahar,Ratovelomanana-Vidal, Virginie,Gaumont, Annie-Claude,Jubault, Philippe,Leclerc, Eric
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experimental part
p. 562 - 574
(2011/06/19)
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- A homogeneous catalyst for reduction of optically active esters to the corresponding chiral alcohols without loss of optical purities
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A ruthenium complex was found to catalyze the hydrogen reduction of esters under mild and neutral conditions. A variety of optically active esters can be reduced to the corresponding alcohols in excellent yield without loss of their optical purity or causing undesirable side reactions. Hydrogen reduction needs such simple operations - reaction, concentration, and purification - that the violent quench step and extraction step, which accompany conventional sodium borohydride or lithium aluminum hydride reduction, can be omitted.
- Kuriyama, Wataru,Ino, Yasunori,Ogata, Osamu,Sayo, Noboru,Saito, Takao
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supporting information; experimental part
p. 92 - 96
(2010/06/17)
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- ALCOHOL PRODUCTION METHOD BY REDUCING ESTER OF LACTONE WITH HYDROGEN
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Provided is an alcohol production method comprising the step of reducing an ester or a lactone with hydrogen to produce a corresponding alcohol without addition of a base compound by using, as a catalyst, a ruthenium complex represented by the following general formula (1): [in-line-formulae]RuH(X)(L1)(L2)n ??(1)[/in-line-formulae] wherein X represents a monovalent anionic ligand,L1 represents a tetradentate ligand having at least one coordinating phosphino group and at least one coordinating amino group or a bidentate aminophosphine ligand having one coordinating phosphino group and one coordinating amino group, andL2 represents a bidentate aminophosphine ligand having one coordinating phosphino group and one coordinating amino group, provided thatn is 0 when L1 is the tetradentate ligand, and n is 1 when L1 is the bidentate aminophosphine ligand.
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Page/Page column 17
(2010/04/23)
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- A large-scale synthesis of enantiomerically pure γ-hydroxy-organochalcogenides
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Enantiomerically pure (R)- and (S)-γ-hydroxy-organochalcogenides are prepared using poly-[R]-3-hydroxybutanoate (PHB) as the starting material.
- Princival, Jefferson L.,de Oliveira, Morilo S.C.,Dos Santos, Alcindo A.,Comasseto, Joao V.
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experimental part
p. 2699 - 2703
(2010/04/29)
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- Asymmetric, catalytic, and direct self-aldol reaction of acetaldehyde catalyzed by diarylprolinol
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(Chemical Equation Presented) An asymmetric, catalytic, and direct self-aldol reaction of acetaldehyde was catalyzed by diarylprolinol in NMP, affording the trimer acetal, which was generated by the reaction of the self-aldol product with another acetaldehyde molecule in a moderate yield with good enantioselectivity. Acetal is the synthetic equivalent of the self-aldol product, which can be converted into other synthetically useful compounds in one pot without compromising the enantioselectivity.
- Hayashi, Yujiro,Samanta, Sampak,Itoh, Takahiko,Ishikawa, Hayato
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supporting information; scheme or table
p. 5581 - 5583
(2009/07/11)
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- Ruthenium complexes of phosphine-aminophosphine ligands
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Ruthenium complexes of phosphinoferrocenylaminophosphine ligands (BoPhoz ligands) have been prepared by combining the ligands with tris(triphenylphosphine)ruthenium dichloride and precipitating the complexes. The optimal species exhibit high enantioselectivities for the asymmetric hydrogenation of functionalized ketones, particularly β-ketoesters.
- Boaz, Neil W.,Ponasik Jr., James A.,Large, Shannon E.
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p. 4033 - 4035
(2007/10/03)
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- Novel (R)-2,3-butanediol dehydrogenase, methods for producing same, and methods for producing optically active alcohol using the dehydrogenase
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The object of the present invention is to provide an (R)-2,3-butanediol dehydrogenase which uses NADH as a coenzyme, and methods for producing optically active alcohols and ketones using the enzyme. The inventors of the present invention discovered a novel (R)-2,3-butanediol dehydrogenase, isolated a DNA encoding the dehydrogenase, and produced recombinants that express the dehydrogenase at high levels. The dehydrogenase is produced by and can be isolated and purified from Kluyveromyces lactis. The use of the dehydrogenase of the invention enables efficient production of (R)-1,3-butanediol with high optical purity from 4-hydroxy-2-butanone. Also provided by the present invention are methods for efficiently producing (S)-1,3-butanediol with high optical purity from racemic 1,3-butanediol, as well as 4-hydroxy-2-butanone from (R)-1,3-butanediol.
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- Diastereoselective route to (2R,5S)- and (2S,5S)-2-methyl-1,6-dioxaspiro[4.5]decane, a pheromone component of the wasp Paravespula vulgaris
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A diastereoselective approach to (2R,5S)- and (2S,5S)-2-methyl-1,6-dioxaspiro[4.5]decane 1 and 1a is described. The route starts with an alkylation reaction among the cyclopentanone N,N-dimethylhydrazone 6 and the chiral iodides (R)-3 or (S)-3, derived from the enantiomers of ethyl β-hydroxybutyrate, controlling the estereocenter at C-2 of the molecules. The alkylated products 7 and 7a were easily transformed into the 1,8-O-TBS-1,8-dihydroxy-5-nonanones 9 and 9a in four steps, and a subsequent stereoselective spiroketalization, in acidic media, afforded a Z:E mixture (1:2) of compounds 1 and 1a.
- Zarbin, Paulo H. G.,De Oliveira, Alfredo R. M.,Delay, Carlos E.
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p. 6849 - 6851
(2007/10/03)
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- Practical application of recombinant whole-cell biocatalysts for the manufacturing of pharmaceutical intermediates such as chiral alcohols
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We have developed efficient biocatalytic processes for the preparation of chiral alcohols, such as (R)-1,3-butanediol, ethyl (S)-4-chloro-3-hyroxybutanoate, ethyl (R)-4-chloro-3-hyroxybutanoate, (S)-5-chloro-2-pentanol, (R)-5-chloro-2-pentanol, and (S)-cyclopropylethanol by stereospecific enzymatic oxidoreduction on a practical level. These chiral alcohols are very important synthons for the synthesis of various pharmaceutical intermediates that lead to antibiotics and inhibitors of HMG-CoA reductase. Here, we present practical applications on biocatalysis using novel recombinant whole-cell biocatalysts that catalyzed enantioselective oxidation and asymmetric reduction with a coenzyme regeneration system.
- Matsuyama, Akinobu,Yamamoto, Hiroaki,Kobayashi, Yoshinori
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p. 558 - 561
(2013/09/06)
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- Synthesis of (R)-1,3-butanediol by enantioselective oxidation using whole recombinant Escherichia coli cells expressing (S)-specific secondary alcohol dehydrogenase
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The synthesis of (R)-1,3-butanediol (BDO) from its racemate was studied using whole cells of recombinant Escherichia coli expressing an (S)-specific secondary alcohol dehydrogenase (CpSADH) from Candida parapsilosis by enantioselective oxidation. Under the optimized conditions, the yield of (R)-1,3-BDO reached 72.6 g/l, with a molar recovery yield of 48.4% from a racemate of 15% and an optical purity of 95% ee.
- Yamamoto, Hiroaki,Matsuyama, Akinobu,Kobayashi, Yoshinori
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p. 925 - 927
(2007/10/03)
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- Lipase mediated resolution of 1,3-butanediol derivatives: Chiral building blocks for pheromone enantiosynthesis. Part 3
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(R,S)-1,3-Butanediol 5 was kinetically resolved by enzymatic acetylation with vinyl acetate under the presence of Chirazyme L-2, c-f, yielding (S)-1-O-acetyl-1,3-hydroxybutane 6 and (R)-1,3-di-O-acetyl-1,3-butanediol 7 with enantiomeric excesses of 91% (E = 67.3). Compounds 6 and 7 were easily transformed into the corresponding (S)-3-O-(2-methoxyethoxymethyl)-3-hydroxybutanal 10 and (R)-3-benzyloxybutanal 19, through a protection-deprotection and functional group interchange methodology. Subsequent reaction of 10 and 19 with 3-(methoxycarbonylpropionylmethylene)triphenylphosphorane afforded methyl (E,S)-8-O-(2-methoxyethoxymethyl)-4-oxo-5-nonenoate 12 and (E,R)-8-benzyloxy-4-oxo-5-nonenoate 20. The alkenes 19 and 20 were then catalytically hydrogenated to the corresponding saturated esters 13 and 21. Treatment of 13 and 21 with 1,2-ethanedithiol/F3B·OEt2 afforded dithioketals 14 and 22, which were respectively reduced to (S)-1,8-dihydroxy-4-nonanone ethylidenedithioketal 15 and (R)-8-O-benzyl-1,8-dihydroxy-4-nonanone ethylidenedithioketal 23. Finally, deprotection of 15 by catalytic hydrogenation under acidic conditions gave the expected (5S,7S)-(-)-7-methyl-1,6-dioxaspiro[4.5]decane 1. The (5R,7R)-(+)-1 enantiomer was analogously prepared from 23. Both compounds were formed by this procedure with an e.e. of 91%.
- Izquierdo, Isidoro,Plaza, Maria T.,Rodriguez, Miguel,Tamayo, Juan A.,Martos, Alicia
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p. 293 - 300
(2007/10/03)
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- Cloning and expression in Escherichia coli of a gene coding for a secondary alcohol dehydrogenase from Candida parapsilosis
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A gene encoding a stereo-specific secondary alcohol dehydrogenase (CpSADH) that catalyzed the oxidation of (S)-1,3-BDO to 4-hydroxy-2-butanone was cloned from Candida parapsilosis. This CpSADH-gene consisted of 1,009 nucleotides coding for a protein with M, 35,964. A recombinant Escherichia coli JM109 strain harboring the expression plasmid, pKK-CPA1, produced (R)-1,3-BDO (93.5% ee, 94.7% yield) from the racemate without any additive to regenerate NAD+ from NADH.
- Yamamoto, Hiroaki,Kawada, Naoki,Matsuyama, Akinobu,Kobayashi, Yoshinori
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p. 1051 - 1055
(2007/10/03)
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- The bakers' yeast reductions of α- and β-keto ester derivatives in the presence of a sulfur compound
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Improvement of the enantioselectivity and enhancement of the reactivity were achieved in the bakers' yeast reduction of the α- and β-keto ester derivatives by the addition of a sulfur compound. High enantioselectivity in the bakers' yeast reduction of keto esters was accomplished by using combination of an addition of a sulfur compound with an appropriate selection of the alcohol part of the ester.
- Hayakawa, Ryuuichirou,Nozawa, Kazumi,Kimura, Kimihiko,Shimizu, Makoto
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p. 7519 - 7528
(2007/10/03)
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- A general synthesis of homochiral β-hydroxy N-acetylcysteamine thioesters
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A convenient and efficient route for the enantioselective synthesis of functionalised β-hydroxy N-acetylcysteamine thioesters is described. The route allows the facile incorporation of vicinal 13C labelling to produce intermediates required for biosynthetic studies on a wide range of polyketide metabolites, e.g. 6-MSA, monocerin, colletodiol and strobilurins.
- Le Sann, Christine,Simpson, Thomas J.,Smith, David I.,Watts, Paul,Willis, Christine L.
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p. 4093 - 4096
(2007/10/03)
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- Toward a total synthesis of an aglycone of spiramycin; a chiron approach to the C-1/C-4 and the C-13/C-15 fragments
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Acetalisation of p-anisaldehyde by either (R) or (S)-butanetriol has been shown to occur selectively and quantitatively by using Noyori's protocol. The crystalline dioxane derivatives R-6a and S-6a which formed respectively in these conditions have been converted efficiently into the title fragments of spiramycin.
- Breullles,Oddon,Uguen
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p. 6607 - 6610
(2007/10/03)
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- Enantioselective oxidation of diols by secondary alcohol dehydrogenase from Geotrichum sp. WF9101
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Geotrichum sp. WF9101 could degrade (S)-(+)-1,2-propanediol, (S)-(+)- 1,3-butanediol, and (2S,4S)-(+)-2,4-pentanediol, but not the corresponding enantiomers. An NAD+-linked secondary alcohol dehydrogenase purified from the strain showed the same enantioselective oxidations towards these diols. This enzyme is proposed to be useful for the preparation of (R)-(-)-diols from the racemates of these diols.
- Mori, Tatsuma,Sakimoto, Michio,Kagi, Takashi,Sakai, Takuo
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p. 1191 - 1192
(2007/10/03)
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- Substrate structure and incubation-parameter-dependent selectivities in chiral discrimination of galactopyranosides by β-galactosidase hydrolysis
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Mono-β-galactopyranosides of (+/-)-propane-1,2-diol, (+/-)-butane-1,3-diol, (+/-)-pentane-1,4-diol, (+/-)-butan-2-ol, (+/-)-pentan-2-ol and (+/-)-1,2-O-isopropylideneglycerol were synthesized by the Koenigs-Knorr reaction using hydroxycarbonyl compounds as precursors for the diolic substrates.Hydrolysis of 3-hydroxybutyl β-D-galactopyranoside 18 by β-galactosidases from Eschrichia coli, Aspergillus oryzae, Kluyveromyces lactis and Bacillus circulans, respectively, resulted in each case in an enantiomeric enrichment of the released diol.This was most significant with the E. coli enzyme and and increased with higher reaction temperature and shorter incubation periods.Under standartized conditions, cleavage of all synthesized galactopyranosides by this enzyme showed the highest stereoselectivity for butane-1,3-diol, butan-2-ol and isopropylideneglycerol with enantiomeric excesses in the range 60-75percent.For compounds with structural similarity to the natural substrate lactose, enhanced stereodiscriminations were expected.However, this could not be confirmed and instead a specific hydrophobic interaction is suggested to play a crucial role.
- Werschkun, Barbara,Koenig, Wilfried A.,Kren, Vladimir,Thiem, Joachim
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p. 2459 - 2466
(2007/10/02)
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- A simple enantioselective synthesis of γ-valerolactone
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The readily available biopolymer, poly-(R)-3-hydroxybutyrate was converted to (R)-(+)-γ-valerolactone in 32% overall yield in a simple 4 stage procedure.
- O'Neill,Lindell,Simpson,Willis
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p. 117 - 118
(2007/10/02)
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- Enantioselective Production of (S)-3-Hydroxybutyric Acid, (S)-1,3-Butanediol and (R)-1,3-Butanediol Using Methanol Yeast
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(S)-3-Hydroxybutyric acid and (S)-1,3-butanediol were obtained by the treatment of 1,3-butanediol with the resting cells of methanol yeast, Candida boidinii (IFO 10574). (R)-1,3-Butanediol was also obtained in high optical purity by the enantioselective reduction of 4-hydroxy-2-butanone in the presence of methanol using the same methanol yeast.
- Matsumura, Shuichi,Imafuku, Hiroshi,Takahashi, Yoshinori,Toshima, Kazunobu
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p. 251 - 254
(2007/10/02)
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- Asymmetric hydrogenation of prochiral carboxylic acids and functionalized carbonyl compounds catalysed by ruthenium(II)-binap complexes with aryl nitriles (binap=(R)- or (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)
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Complexes RuCl2(ArCN)2(binap), II (binap=(R)- or (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl; ArCN=benzonitrile, a; 2-furancarbonitrile, b; pentafluorobenzonitrile, c) were prepared, and their solution properties were investigated by 31P NMR measurements.The catalytic aactivities and enantioselectivities for IIa-c catalysed hydrogenation of some prochiral acids were very similar to those provided by Ru2Cl4(binap)2(NEt3), I.In the hydrogenation of β-functionalized carbonyl compounds, however, IIa-c showed considerably lower activities and/or selectivities, compared with complex I.The differences in IIa-c catalysed reactions are discussed in relation to the coordinating abilities of ArCN in II.
- Shao, Liming,Takeuchi, Kasumi,Ikemoto, Makoto,Kawai, Toshiyasu,Ogasawara, Masamichi,et al.
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p. 133 - 147
(2007/10/02)
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- Stereoselective Acetalization of 1,3-Alkanediols by l-Menthone: Application to the Resolution of Racemic 1,3-Alkanediols and to the Determination of the Absolute Configuration of Enantiomeric 1,3-Alkanediols
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A general and reliable method for the resolution of racemic 1,3-alkanediols, which involves their conversion into diastereomeric spiroacetals derived from l-menthone, is described.Thus, the reaction of the bis-O-trimethylsilyl derivatives of racemic 1,3-alkanediols with l-menthone in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate affords the diastereomeric spiroacetals 3 and 4.The two can be readily separated by silica gel column chromatography.Hydrolysis of each diastereomer under acidic conditions liberates the corresponding enantiomerically pure diol.An empirically derived correlation of configuration and 1H NMR chemical shifts for spiroacetals 3 and 4 has been developed which is rationalized based on long-range effects due to the magnetic anisotropy inherent to the menthane ring in a rigid spiroacetal conformation.The method described here should be widely applicable to the determination of the absolute configuration of various 1,3-alkanediols.
- Harada, Toshiro,Kurokawa, Hideaki,Kagamihara, Yasuhiro,Tanaka, Sachi,Inoue, Atsushi,Oku, Akira
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p. 1412 - 1421
(2007/10/02)
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- Asymmetric intramolecular hydrosilylation of hydroxyketones
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A procedure for the catalytic asymmetric intramolecular hydrosilylation of α- and β-hydroxyketones has been developed. A cationic rhodium (I) catalyst bearing the new chiral diphosphine (R,R)-i-Pr-DuPHOS affords the product diols in up to 93% ee.
- Burk, Mark J.,Feaster, John E.
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p. 2099 - 2102
(2007/10/02)
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- CONVENIENT PREPARATION OF BINAP-RUTHENIUM(II) COMPLEXES CATALYZING ASYMMETRIC HYDROGENATION OF FUNCTIONALIZED KETONES
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Ligand exchange between 2 or RuCl23 and (R)- or (S)-BINAP produces BINAP-Ru(II) complexes which act as catalysts for the highly enantioselective hydrogenation of functionalized ketones.
- Kitamura, M.,Tokunaga, M.,Ohkuma, T.,Noyori, R.
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p. 4163 - 4166
(2007/10/02)
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- (S)-β,ω-Dihydroxyalkyl Phenyl Sulfones. Synthesis by Bakers' Yeast Reduction and Use as Precursors of Optically Active Lactones
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The enantioselective reduction of ω-hydroxy-β-ketoalkyl phenyl sulfones with bakers' yeast gives (S)-ω,β-dihydroxyalkyl phenyl sulfones, which are convenient precursors for optically active lactones as shown in the synthesis of (R)-4-hexanolide and (R)-umbelactone.
- Sato, Toshio,Okumura, Yoshiyuki,Itai, Junichi,Fujisawa, Tamotsu
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p. 1537 - 1540
(2007/10/02)
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- A NEW SYNTHESIS OF BOTH THE ENANTIOMERS OF GRANDISOL, THE BOLL WEEVIL PHEROMONE
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The pure enantiomers of grandisol (2-isopropenyl-1-methylcyclobutane-ethanol), the pheromone component of Anthonomus grandis Boheman, were synthesized employing ethyl (R)-3-hydroxybutanoate as the single chiral source.
- Mori, Kenji,Miyake, Masahiro
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p. 2229 - 2240
(2007/10/02)
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- RESOLUTION OF 1,3-ALKANEDIOLS VIA CHIRAL SPIROKETALS DERIVED FROM l-MENTHONE
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Ketalization reaction of racemic 1,3-alkanediols with l-menthone gave a mixture of diastereomeric spiroketals that was easily separated by silica gel column chromatography and converted into enantiomerically pure diols by acid-catalyzed hydrolysis.
- Harada, Toshiro,Kurokawa, Hideaki,Oku, Akira
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p. 4843 - 4846
(2007/10/02)
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- AN ENANTIODIFFERENTIATING CONVERSION OF RACEMIC 1,3-ALKANEDIOLS INTO ENANTIOMERICALLY PURE MATERIALS
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Titanium tetrachloride promoted ring-cleavage reaction of a mixture of diastereomeric spiroketals derived from racemic 1,3-alkanediols and l-menthone, followed by benzoylation by Mitsunobu reaction, and the subsequent hydrolysis gave enantiomerically pure 1,3-alkanediols.
- Harada, Toshiro,Kurokawa, Hideaki,Oku, Akira
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p. 4847 - 4848
(2007/10/02)
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- Access to (S)-2-Methyloxetane and the Precursor (S)-1,3-Butanediol of Hight Enantiomeric Purity
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(S)-2-Methyloxetane (1) and its precursor (S)-1,3-butanediol (2) were prepared in low to moderate chemical yield with less than 0.5percent racemization from (S)-ethyl lactate (4) and from (2S,3S)-allothreonine (14b).For the first time the enantiomeric purities of both the starting material and the product (1) were carefully determined by high-precision capillary gas chromatography on optically active resolving stationary phases.The validity of the quadrant rule, correlating the relative configuration of alkyloxiranes with the order of elution from manganese(II) bis (3) by complexation gas chromatography, is also confirmed for 2-methyloxetane (1).
- Hintzer, Klaus,Koppenhoefer, Bernhard,Schurig, Volker
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p. 3850 - 3854
(2007/10/02)
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- Stereochemistry of Friedel-Crafts Reaction of Benzene with Optically Active 2-Methyloxetane
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The Friedel-Crafts alkylation of benzene with (+)-2-methyloxetane in the presence of Lewis acids (AlCl3, SnCl4, and TiCl4) gave 3-phenyl-1-butanol with 20-60percent inversion of configuration at the reaction center and a mixture of 4-chloro-2-butanol and 3-chloro-1-butanol in optically active form as the by-products. These by-products were formed by the attack of the chlorine atom in Lewis acid. The stereochemical course of the reaction to 3-chloro-1-butanol varied with the kind of catalyst, i.e., inversion with AlCl3 or TiCl4 and retention with SnCl4. The addition of nitromethane to the reaction system promoted the retentive ring-opening to 3-chloro-1-butanol.
- Segi, Masahito,Takebe, Masaki,Masuda, Shinji,Nakajima, Tadashi,Suga, Sohei
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p. 167 - 170
(2007/10/02)
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- Asymmetric Synthesis. Asymmetric Catalytic Hydrogenation Using Chiral Chelating Six-Membered Ring Diphosphines
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Rhodium(I) catalysts formed by the two chiral chelating six-membered ring diphosphines, 2,4-bis(diphenylphosphino)pentane (skewphos) and 1,3-bis(diphenylphosphino)butane (chairphos), are efficient catalysts for the hydrogenation of amino acid precursors.The two chiral phosphines differ in that skewphos probably adopts a chiral conformation whereas chairphos probably adopts an achiral conformation.This comparison evidences the importance of ring conformations in determining optical yields.The mechanism of asymmetric hydrogenation is discussed, and a number of particular and general conclusions are drawn which may prove useful in predicting optical yields from asymmetric synthesis.
- MacNeil, Patricia A.,Roberts, Nicholas K.,Bosnich, B.
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p. 2273 - 2280
(2007/10/02)
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- Enantiomerically Pure Synthetic Building Blocks with Four C-Atoms and Two or Three Functional Groups from β-Hydroxy-butanoic, Malic, and Tartaric Acid
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The pool of chiral, non-racemic electrophilic building blocks, which are available from simple natural products in both enantiomeric forms is enlarged by the epoxides 3, 5, and 10, by the tosylate 12a, and by the aldehydes 18 (cf. symbols A-D, 14, and Scheme 1).Key steps of the conversions leading from hydroxyacids to the building blocks are: epoxide-opening by triethylborohydride (1 --> 2a) and tosylate reduction (12a --> 12b); the Mitsunobu inversion (2a --> 4a); the reduction of (R,R)-tartaric ester to (R)-malic ester by NBS (N-bromosuccinimide) opening of the benzaldehyde acetal 8 and tin hydride reduction (6c -->7c); the enantiomer enrichment of optically active ethyl β-hydroxy-butanoate through the crystalline dinitrobenzoate 21b.Detailed procedures are given for large scale preparations of the key intermediates.The enantiomeric purities of the building blocks are secured by correlations.
- Hungerbuehler, Ernst von,Seebach, Dieter,Wasmuth, Daniel
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p. 1467 - 1487
(2007/10/02)
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- The Enantioface-differentiating Hydrogenation of the C=O Double Bond with Asymmetrically Modified Raney Nickel.XXXIII.The Preparation of (R)-and (S)-1,3-Butanediol from 4-Hydroxy-2-butanone
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The enantioface-differentianing hydrogenation of 4-hydroxy-2-butanone (I) to 1,3-butanediol (II) was conduced with asymmetrically modified metal catalysts.Among the modified catalysts examined, Raney nickel modified with a solution containing tartaric acid and NaBr (TA-NaBr-MRNi) gave the best results with respect to the optical and chemical yields. (R)-II, an optical purity of 69 percent was obtained in a quantitative chemical yeld by the use of (R,R)-TA-NaBr-MRNi. (S)-II was also obtained by the use of (S,S)-TA-NaBr-MRNi.A simple method for the preparation of optically pure (S)- and (R)-II from the hydrogenation product was also developed.
- Murakami, Shigeki,Harada, Tadao,Tai, Akira
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p. 1356 - 1360
(2007/10/02)
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