- Method for preparing 4-chiral substituted gamma-butyrolactone
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The invention discloses a method for preparing 4-chiral substituted gamma-butyrolactone. The method comprises the following steps: (a) performing chiral reduction on substituted succinic anhydride serving as a raw material to obtain a compound 2; (b) preparing a corresponding compound 3 from the compound 2 by a reaction of transforming hydroxyl into amino; (c) performing chiral resolution on the compound 3 through chiral solution acids to obtain a compound 4; and (d) performing a deamination reaction on the compound 4 to obtain a final product compound 5. The substituent group R is selected from C1-C8 straight-chain or branched alkyl, 3-8 component alicyclic group, aryl, heteroaryl, Ar(CH2)n-radical, wherein Ar represents aryl and heteroaryl, and n equals to 1-6. The invention provides a novel synthesizing route, raw materials are easily available, and conventional substituted succinic anhydride has bulk production; the operation steps are conventional chemical reactions, are simple and easy and have strong operability; and a final product has good chiral selectivity, has an ee value of between 85-99.5 percent, and has high purity.
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- First chemo-enzymatic synthesis of the (R)-Taniguchi lactone and substrate profiles of CAMO and OTEMO, two new Baeyer–Villiger monooxygenases
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Abstract: This study investigates the substrate profile of cycloalkanone monooxygenase and 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A monooxygenase, two recently discovered enzymes of the Baeyer–Villiger monooxygenase family, used as whole-cell biocatalysts. Biooxidations of a diverse set of ketones were performed on analytical scale: desymmetrization of substituted prochiral cyclobutanones and cyclohexanones, regiodivergent oxidation of terpenones and bicyclic ketones, as well as kinetic resolution of racemic cycloketones. We demonstrated the applicability of the title enzymes in the enantioselective synthesis of (R)-(?)-Taniguchi lactone, a building block for the preparation of various natural product analogs such as ent-quinine. Graphical abstract: [Figure not available: see fulltext.]
- Rudroff, Florian,Fink, Michael J.,Pydi, Ramana,Bornscheuer, Uwe T.,Mihovilovic, Marko D.
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p. 157 - 165
(2017/01/17)
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- Enantioselective α-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes
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The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin. A combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective cyanoalkylation of aldehydes. This synergistic catalysis protocol makes possible the coupling of two highly versatile yet orthogonal functionalities.
- Welin, Eric R.,Warkentin, Alexander A.,Conrad, Jay C.,MacMillan, David W. C.
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p. 9668 - 9672
(2015/08/11)
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- Organocatalytic Enantioselective Alkylation of Aldehydes with [Fe(bpy)3]Br2 Catalyst and Visible Light
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Catalytic amounts (2.5 mol %) of [Fe(bpy)3]Br2 complex in the presence of visible light and the MacMillan catalyst 3 (20 mol %) are highly effective in promoting an enantioselective organocatalytic photoredox alkylation of aldehydes
- Gualandi, Andrea,Marchini, Marianna,Mengozzi, Luca,Natali, Mirco,Lucarini, Marco,Ceroni, Paola,Cozzi, Pier Giorgio
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p. 5927 - 5931
(2015/10/12)
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- Type II flavin-containing monooxygenases: A new class of biocatalysts that harbors baeyer-villiger monooxygenases with a relaxed coenzyme specificity
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Within a newly identified set of flavin-containing monooxygenases (FMOs) from Rhodococcus jostii RHA1, we have identified three monooxygenases (FMO-E, FMO-F, and FMO-G) that are effective in catalyzing Baeyer-Villiger oxidations. These type II FMOs display relaxed coenzyme specificity by accepting both NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) and NADH (reduced form of nicotinamide adenine dinucleotide), as a coenzyme, which is a novel and attractive feature among biocatalysts capable of conducting Baeyer-Villiger oxidations. We purified FMO-E and determined that the Michaelis constants for both coenzymes were in the micromolar range, whereas the activity was highest for NADH. By using the stopped-flow technique, formation of a peroxyflavin-enzyme intermediate was observed, which indicated that type II FMOs follow a catalytic mechanism similar to that of other class B flavoprotein monooxygenases. A set of cyclobutanones and cyclohexanones were used to probe the regio- and enantioselectivity of all three recombinant monooxygenases. The biocatalysts readily accepted small cyclic ketones, which enabled the conversion of previously poorly accepted substrates by other monooxygenases (especially norcamphor), and exhibited excellent and unique regio- and enantioselectivities. Sequence analysis revealed that type II FMOs that act as Baeyer-Villiger monooxygenases contain a unique N-terminal domain. Sequence conservation in this protein domain can be used to identify new NADH-dependent Baeyer-Villiger monooxygenases, which would facilitate future biocatalyst discovery efforts. New kid on the block: Members of a newly recognized group of sequence-related flavin-containing monooxygenases can perform Baeyer-Villiger oxidations. Their coenzyme indifference and unique specificity make them attractive biocatalysts.
- Riebel, Anette,Fink, Michael J.,Mihovilovic, Marko D.,Fraaije, Marco W.
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p. 1112 - 1117
(2014/05/06)
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- γ-Selective directed catalytic asymmetric hydroboration of 1,1-disubstituted alkenes
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Directed catalytic asymmetric hydroborations of 1,1-disubstituted alkenes afford γ-dioxaborato amides and esters in high enantiomeric purity (90-95% ee). The Royal Society of Chemistry 2012..
- Smith, Sean M.,Hoang, Gia L.,Pal, Rhitankar,Khaled, Mohammad O. Bani,Pelter, Liberty S. W.,Zeng, Xiao Cheng,Takacs, James M.
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p. 12180 - 12182
(2013/01/16)
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- Self-sufficient Baeyer-Villiger monooxygenases: Effective coenzyme regeneration for biooxygenation by fusion engineering
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(Chemical Presented) Two-in-one biocatalysts were engineered by the covalent fusion of NADPH-dependent Baeyer-Villiger monooxygenases to a phosphite dehydrogenase for coenzyme regeneration (see scheme). Not only the purified fusion proteins, but also whole cells and crude cell extracts containing the enzyme conjugates, could be used to catalyze biotransformations with high efficiency. NADP+=nicotinamide adenine dinucleotide phosphate.
- Torres Pazmino, Daniel E.,Snajdrova, Radka,Baas, Bert-Jan,Ghobrial, Michael,Mihovilovic, Marko D.,Fraaije, Marco W.
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supporting information; scheme or table
p. 2275 - 2278
(2009/02/08)
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- A facile chemoenzymatic approach to chiral non-racemic β-alkyl-γ-amino acids and 2-alkylsuccinic acids. A concise synthesis of (S)-(+)-Pregabalin
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Both enantiomerically pure antipodes of GABA analogues were prepared as hydrochloride salts, by enzymatic kinetic resolution of their precursors ethyl 2-(nitromethyl)alkanoates. These latter compounds can be easily transformed into enantiomerically pure 2-alkylsuccinic acids by a Nef reaction followed by oxidation. Interestingly, this reaction was particularly easy for the neopentyl derivative (S)-(+)-7d, which underwent conversion into its corresponding succinic acid derivative (S)-(-)-8d in buffered solution. The absolute configurations of the main compounds of interest involved are given, together with their CD spectra.
- Felluga, Fulvia,Pitacco, Giuliana,Valentin, Ennio,Venneri, Cesare Daniele
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p. 945 - 955
(2008/09/21)
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- Comparing the stereoselective biooxidation of cyclobutanones by recombinant strains expressing bacterial baeyer - Villiger monooxygenases
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Microbial Baeyer - Villiger oxidation of representative prochiral ketones with a cyclobutanone structural motif was investigated using a collection of eight monooxygenases of different bacterial origin. This platform of enzymes is able to perform stereoselective biotransformations on an array of structurally diverse substrates. With several ketone precursors, biooxidations yielded enantiocomplementary butyrolactones as key intermediates for the synthesis of natural products and bioactive compounds. The microbial Baeyer - Villiger oxidation allows a facile and rapid entry to several compound classes in a desymmetrization reaction upon de novo generation of chirality.
- Rudroff, Florian,Rydz, Joanna,Ogink, Freek H.,Fink, Michael,Mihovilovic, Marko D.
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p. 1436 - 1444
(2008/09/17)
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- Catalytic enantioselective conjugate reduction of lactones and lactams
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A dramatic acceleration of the enantioselective copper-catalyzed conjugate reduction of α,β-unsaturated lactones, lactams, and esters is reported upon addition of alcohol additives. Good to excellent yields and enantioselectivities were realized using a catalyst generated in situ from CuCl2·H2O, t-BuONa, p-tol-BINAP, and PMHS, and this methodology was applied to the synthesis of (-)-Paroxetine.
- Hughes, Gregory,Kimura, Masanari,Buchwald, Stephen L.
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p. 11253 - 11258
(2007/10/03)
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- Concise synthesis of (+)-β-benzyl γ-butyrolactones from butynediol
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The synthesis of optically active β-benzyl-γ-butyrolactones from butynediol via four transition metal catalysed reactions is reported. Key reactions are the hitherto unknown enantioselective hydrogenation of 2-benzyl-2-buten-1,4-diols using Ir(I) phosphinooxazoline catalysts and the regiocontrolled oxidation of the resulting 2-benzyl-1,4-butanediols to the β-substituted butyrolactones.
- Kamlage,Sefkow,Zimmermann,Peter
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- First attempts at differential diastereoselection in catalytic reactions of N-chirally substituted dirhodium(II) tetrakis[methyl 2-oxoimidazolidine-4(S)-carboxylates] with diazoacetates
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Chiral attachments on 2-oxoimidazolidine-4(S)-carboxylate ligands for dirhodium(II) can provide differential diastereoselection in catalytic reactions of diazo compounds. The synthesis of these heterocyclic ligands from the readily available amino acid as
- Doyle,Timmons,Arndt,Duursma,Colyer,Bruenner
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p. 2156 - 2161
(2007/10/03)
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- Enantioselective Baeyer-Villiger oxidations catalyzed by chiral magnesium complexes
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Catalytic enantioselective Baeyer-Villiger oxidations of 3-substituted cyclobutanones with cumene hydroperoxide as oxidant have successfully been performed in the presence of chiral magnesium catalysts. The combination of enantiopure BINOL and a variety o
- Bolm,Beckmann,Cosp,Palazzi
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p. 1461 - 1463
(2007/10/03)
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- Synthesis of optically active β-benzyl-γ-butyrolactone through lipase-catalyzed kinetic resolution
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The lipase-catalyzed kinetic resolution of the racemic γ-hydroxy ester 2, coupled with subsequent acid-mediated cyclization, is an effective method for the synthesis of both enantiomers of β-benzyl-γ-butyrolactone 1. This enzymatic process affords the pro
- Caro, Yolanda,Masaguer, Christian F.,Ravia, Enrique
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p. 1723 - 1726
(2007/10/03)
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- Enantioselective synthesis of benzylbutyrolactones from 5-hydroxyfuran-2(5H)-one. New chiral synthons for dibenzylbutyrolactone lignans by a chemoenzymatic route
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A chemoenzymatic method is described for the asymmetric synthesis of benzylbutyrolactones. (R)-5-Acetoxyfuran-2(5H)-one (12) was obtained with ee > 99% in a multigram scale catalytic esterification using immobilized lipase PS. The addition of lithiated dithianes to chiral synthon 12 was followed by an effective multistep reduction to produce enantiomerically pure benzylbutyrolactones.
- Brinksma, Jelle,Van Der Deen, Hanneke,Van Oeveren, Arjan,Feringa, Ben L.
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p. 4159 - 4163
(2007/10/03)
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- Oxidation of some prochiral 3-substituted cyclobutanones using monooxygenase enzymes: a single-step method for the synthesis of optically enriched 3-substituted γ-lactones
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Oxidation of the prochiral cyclobutanones 1-5 using Acinetobacter calcoaceticus NCIMB 9871 and Pseudomonas putida NCIMB 10007 monooxygenases (MO1 and MO2) furnishes the corresponding lactones 6-10 in moderate to excellent yield and enantiomeric purity.The
- Gagnon, Rene,Grogan, Gideon,Groussain, Esther,Pedragosa-Moreau, Sandrine,Richardson, Paul F.,et al.
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p. 2527 - 2528
(2007/10/02)
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- A New Methodology for the Construction of Chiral 4-Benzyl-2-furanone via C2-Symmetric Bis-Radical Intermediate
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A new methodology leading to optically pure 4-benzyl-2-furanone has been developed by employing intramolecular reaction intervening C2-Symmetric bis-radical intermediate derived from diethyl (L)-tartrate.
- Takano, Seiichi,Ohashi, Kazuko,Sugihara, Takumichi,Ogasawara, Kunio
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p. 203 - 206
(2007/10/02)
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