100306-33-0Relevant articles and documents
Identification of key residues in Debaryomyces hansenii carbonyl reductase for highly productive preparation of (S)-aryl halohydrins
Xu, Guo-Chao,Shang, Yue-Peng,Yu, Hui-Lei,Xu, Jian-He
, p. 15728 - 15731 (2015)
Key residues of Debaryomyces hansenii carbonyl reductase in the determination of the reducing activity towards aryl haloketones were identified through combinatorial mutation of conserved residues. This study provides a green and efficient biocatalyst for the synthesis of (S)-aryl halohydrins.
PEG600-carboxylates as efficient reusable reaction media and acylating agents for the resolution of sec-alcohols
Monteiro, Carlos M.,Lourenco, Nuno M. T.,Ferreira, Frederico C.,Afonso, Carlos A. M.
, p. 42 - 46 (2015)
Herein is presented a simple, attractive, and reusable methodology for one-pot resolution/separation of free sec-alcohols with enantiomeric excess (ee) values over 90% by the combination of sustainable acylating agents/solvents (polyethylene glycol derivatives) and an easily available and common biocatalyst (Candida antarctica lipase B, or CAL B) under irreversible conditions, along with a separation process by extraction or distillation. A scale-up reaction was carried out with the Fluoxetine precursor with ee values close to 90% for the R enantiomer.
A new catalytic enantioselective reducing reagent system from (-)-α,α-diphenylpyrrolidinemethanol and 9-borabicyclo[3.3.1]nonane, especially effective for hindered and substituted aralkylketones
Kanth, Josyula V.B.,Brown, Herbert C.
, p. 1069 - 1074 (2002)
New catalytic enantioselective reduction systems were prepared from aminoalcohols and dialkylboranes, for the enantioselective reductions of prochiral aromatic ketones. Among these, the system prepared from (-)-α,α-diphenylpyrrolidinemethanol with 9-borabicyclo[3.3.1]nonane proved especially promising for such reductions. This complex catalyzes the reduction of prochiral aralkyl ketones to the corresponding alcohols with BH3-THF, with enantioselectivities 82-99.2%. Also, this catalyst is particularly effective for the more hindered and substituted aralkyl ketones. Various modifications in this new catalytic reduction system, such as changing reaction conditions, reducing agent and dialkylborane, were also examined.
Pen G acylase catalyzed resolution of phenylacetate esters of secondary alcohols
Baldaro,D'Arrigo,Pedrocchi-Fantoni,Rosell,Tagliani,Terreni,Servi
, p. 1031 - 1034 (1993)
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.
Chemoenzymatic synthesis of fluoxetine precursors. Reduction of β-substituted propiophenones
Coronel, Camila,Arce, Gabriel,Iglesias, Cesar,Noguera, Cynthia Magallanes,Bonnecarrere, Paula Rodriguez,Giordano, Sonia Rodriguez,Gonzalez, David
, p. 94 - 98 (2014)
Five endophytic yeast strains isolated from edible plants were tested in the reduction β-chloro- and β-azidopropiophenone for the preparation of optically active fluoxetine precursors. The biotransformation rendered not only the corresponding chiral γ-substituted alcohols, but also unsubstituted alcohols and ketones. The product profile was studied and a plausible mechanism for the reductive elimination of the β-functional group is proposed.
Asymmetric Synthesis of 2-Aryl Substituted Oxetanes by Enantioselective Reduction of β-Halogenoketones using Lithium Borohydride modified with N,N'-Dibenzoylcystine
Soai, Kenso,Niwa, Seiji,Yamanoi, Takashi,Hikima, Hitoshi,Ishizaki, Miyuki
, p. 1018 - 1019 (1986)
Optically active 2-aryl substituted oxetanes are synthesised in high enantiomeric excesses (up to 89percent e.e.) via enantioselective reduction of β-halogenoketones with lithium borohydride using (R,R')-N,N'-dibenzoylcystine and t-butyl alcohols as ligands.
Facile access to chiral alcohols with pharmaceutical relevance using a ketoreductase newly mined from Pichia guilliermondii
Xu, Guochao,Yu, Huilei,Xu, Jianhe
, p. 349 - 354 (2013)
Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y-324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2-bromoacetophenone (93.5% ee). Semi-preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers. Copyright
Chiral N-heterocyclic carbene iridium catalyst for the enantioselective hydrosilane reduction of ketones
Manabe, Yoshiki,Shinohara, Kanako,Nakamura, Hanako,Teramoto, Hiro,Sakaguchi, Satoshi
, p. 138 - 145 (2016)
Enantioselective reduction of ketones with (EtO)2MeSiH catalyzed by an in-situ generated N-heterocyclic carbene (NHC) Ir complex at room temperature has been developed. A series of benzimidazolium salts were synthesized and screened in the asymmetric hydrosilylation reaction. As a result, propiophenone was efficiently reduced by the combined catalytic system of [IrCl(cod)]2 and NHC-Ag complex derived from N-(1-naphthalenylmethyl)-substituted benzimidazolium salt L12, affording the corresponding alcohol in 92% yield and with 92% ee. Moreover, the evaluation of an Ir catalyst precursor showed that cationic [Ir(cod)2]BF4 complex could be used. Furthermore, the introduction of a chiral hydroxyamide side arm into the benzimidazolium salt was critical for the successful design of the NHC ligand.
Diphenyloxazaborolidine a new catalyst for enantioselective reduction of ketones
Quallich, George J.,Woodall, Teresa M.
, p. 4145 - 4148 (1993)
A variety of ketones can be reduced in high enantioselectivity with the oxazaborolidines derived from commercially available erythro aminodiphenylethanol.
Ultrafast Iron-Catalyzed Reduction of Functionalized Ketones: Highly Enantioselective Synthesis of Halohydrines, Oxaheterocycles, and Aminoalcohols
Blasius, Clemens K.,Vasilenko, Vladislav,Gade, Lutz H.
, p. 10231 - 10235 (2018)
A molecularly defined chiral boxmi iron alkyl complex catalyzes the hydroboration of various functionalized ketones and provides the corresponding chiral halohydrines, oxaheterocycles (oxiranes, oxetanes, tetrahydrofurans, and dioxanes) and amino alcohols with excellent enantioselectivities (up to >99 %ee) and conversion efficiencies at low catalyst loadings (as low as 0.5 mol %). Turnover frequencies of greater than 40000 h?1 at ?30 °C highlight the activity of this earth-abundant metal catalyst which tolerates a large number of functional groups.
Asymmetric reduction of prochiral ketones using in situ generated oxazaborolidine derived from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol. An efficient synthesis of enantiopure (R)-tomoxetine
Lapis, Alexandre A. M.,De Fátima, ?ngelo,Martins, José E. D.,Costa, Valentim E. U.,Pilli, Ronaldo A.
, p. 495 - 498 (2005)
In this work, we report our results on the asymmetric reduction of prochiral aromatic and aliphatic ketones 3, 5-8 catalyzed by the novel in situ generated oxazaborolidine 2 derived from (1S,2S,3R,4R)-3-amino-7,7- dimethoxybornan-2-ol (1) and BH3?Me2S. This methodology was applied to the synthesis of the anti-depressant drug (R)-tomoxetine in three steps and 47% overall yield from 3-chloropropiophenone (3h). Catalytic asymmetric reduction of prochiral ketones was examined in the presence of chiral oxazaborolidine catalyst 2 prepared in situ from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol (1). The optically active secondary alcohols were generally obtained in moderate to high enantiomeric excesses (ee 43-95%) and good yields (75-94%), except for ketones bearing electron-withdrawing groups. The methodology was applied to the synthesis of enantiopure (R)-tomoxetine, a potent anti-depressant drug.
Total Synthesis of Meayamycin B
Basu, Upamanyu,Bressin, Robert K.,Koide, Kazunori,Osman, Sami,Pohorilets, Ivanna
supporting information, p. 4637 - 4647 (2020/05/01)
Meayamycin B is currently the most potent modulator of the splicing factor 3b subunit 1 and used by dozens of research groups. However, current supply for this natural product analogue is limited because of the lengthy synthetic scheme. Here, we report a more concise, more cost-effective, and greener synthesis of this compound by developing and employing a novel asymmetric reduction of a prochiral enone to afford an allylic alcohol with high enantioselectivity. In addition to this reaction, this synthesis highlights a scalable Mukaiyama aldol reaction, Nicolaou-type epoxide opening reaction, stereoselective Corey-Chaykovsky-type reaction, and a modified Horner-Wadsworth-Emmons Z-selective olefination. We also discuss a Z-E isomerization during the α,β-unsaturated amide formation. The new synthesis of meayamycin B consists of 11 steps in the longest linear sequence and 24 total steps.
Iridium-Catalyzed Asymmetric Hydrogenation of Halogenated Ketones for the Efficient Construction of Chiral Halohydrins
Yin, Congcong,Wu, Weilong,Hu, Yang,Tan, Xuefeng,You, Cai,Liu, Yuanhua,Chen, Ziyi,Dong, Xiu-Qin,Zhang, Xumu
supporting information, p. 2119 - 2124 (2018/04/30)
Iridium-catalyzed asymmetric hydrogenation of prochiral halogenated ketones was successfully developed to prepare various chiral halohydrins with high reactivities and excellent enantioselectivities under basic reaction condition (up to >99% conversion, 99% yield, >99% ee). Moreover, gram-scale experiment was performed well in the presence of just 0.005 mol% (S/C=20 000) Ir/f-amphox catalyst with 99% yield and >99% ee. (Figure presented.).