- PQQ-dependent Dehydrogenase Enables One-pot Bi-enzymatic Enantio-convergent Biocatalytic Amination of Racemic sec-Allylic Alcohols
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The asymmetric amination of secondary racemic allylic alcohols bears several challenges like the reactivity of the bi-functional substrate/product as well as of the α,β-unsaturated ketone intermediate in an oxidation-reductive amination sequence. Heading for a biocatalytic amination cascade with a minimal number of enzymes, an oxidation step was implemented relying on a single PQQ-dependent dehydrogenase with low enantioselectivity. This enzyme allowed the oxidation of both enantiomers at the expense of iron(III) as oxidant. The stereoselective amination of the α,β-unsaturated ketone intermediate was achieved with transaminases using 1-phenylethylamine as formal reducing agent as well as nitrogen source. Choosing an appropriate transaminase, either the (R)- or (S)-enantiomer was obtained in optically pure form (>98 % ee). The enantio-convergent amination of the racemic allylic alcohols to one single allylic amine enantiomer was achieved in one pot in a sequential cascade.
- Gandomkar, Somayyeh,Rocha, Raquel,Sorgenfrei, Frieda A.,Montero, Lía Martínez,Fuchs, Michael,Kroutil, Wolfgang
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p. 1290 - 1293
(2020/12/23)
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- Iterative Alanine Scanning Mutagenesis Confers Aromatic Ketone Specificity and Activity of L-Amine Dehydrogenases
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Direct reductive amination of prochiral ketones catalyzed by amine dehydrogenases is attractive in the synthesis of active pharmaceutical ingredients. Here, we report the protein engineering of L-Bacillus cereus amine dehydrogenase to allow reactivity on synthetically useful aromatic ketone substrates using an iterative, multiple-site alanine scanning mutagenesis approach. Mutagenesis libraries based on molecular docking, iterative alanine scanning, and double-proximity filter approach significantly expand the scope of active pharmaceutical ingredients relevant building blocks. The eventual quintuple mutant (A115G/T136A/L42A/V296A/V293A) showed reactivity toward aromatic ketones 12 a (5-phenyl-pentan-2-one) and 13 a (6-phenyl-hexan-2-one), which have not been reported to serve as targets of reductive amination by currently available amine dehydrogenases. Docking simulation and tunnel analysis provided valuable insights into the source of the acquired specificity and activity.
- Mu, Xiaoqing,Wu, Tao,Mao, Yong,Zhao, Yilei,Xu, Yan,Nie, Yao
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p. 5243 - 5253
(2021/11/16)
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- Sequential Two-Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases
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A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.
- Albarrán-Velo, Jesús,Lavandera, Iván,Gotor-Fernández, Vicente
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p. 200 - 211
(2019/12/03)
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- Kinetic resolution of primary allylic amines via palladium-catalyzed asymmetric allylic alkylation of malononitriles
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A range of primary allylic amines were resolved with selectivity factors of up to 491 through [Pd(allyl)Cl]2/(S)-BINAP-catalyzed and mesitylsulfonyl hydrazide-accelerated asymmetric allylic alkylation of malononitriles involving enantioselectiv
- Wang, Yong,Xu, Ya-Nan,Fang, Guo-Sheng,Kang, Hong-Jian,Gu, Yonghong,Tian, Shi-Kai
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supporting information
p. 5367 - 5371
(2015/05/20)
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- Deammoniative condensation of primary allylic amines with nonallylic amines
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An unprecedented deammoniative condensation reaction of primary allylic amines with nonallylic amines has been developed through C-N bond cleavage. In the presence of 5 mol% palladium diacetate, 10 mol% 1,4-bis(diphenylphosphino) butane (dppb), and 5 mol% p-toluenesulfonic acid (TsOH), a range of α-unbranched primary allylic amines smoothly underwent deammoniative condensation with nonallylic amines in an α-selective fashion to give structurally diverse secondary and tertiary amines in good to excellent yields and E selectivity. Replacing dppb with racemic 2,2-bis(diphenylphosphino)-1,1- binaphthyl (BINAP) permitted the deammoniative condensation of enantioenriched α-chiral primary allylic amines with nonallylic amines to proceed with complete retention of configuration. Electrospray ionization (ESI) mass spectrometric analysis of the reaction mixture permitted the identification of some π-allylpalladium intermediates, and plausible mechanisms have been proposed to account for the regioselectivity and stereospecificity of the deammoniative condensation reaction. A range of enantioenriched primary allylic amines underwent palladium/acid-catalyzed direct substitution with nonallylic amines in a stereospecific manner. Copyright
- Wang, Yong,Li, Manbo,Ma, Xiantao,Liu, Congrong,Gu, Yonghong,Tian, Shi-Kai
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p. 741 - 751
(2014/10/15)
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- Palladium-catalyzed aerobic oxidative coupling of enantioenriched primary allylic amines with sulfonyl hydrazides leading to optically active allylic sulfones
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A range of highly enantioenriched primary allylic amines underwent palladium-catalyzed oxidative coupling with sulfonyl hydrazides open to air at room temperature to give structurally diverse allylic sulfones in moderate to excellent yields with excellent retention of ee. This journal is the Partner Organisations 2014.
- Wang, Ting-Ting,Wang, Fu-Xiang,Yang, Fu-Lai,Tian, Shi-Kai
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supporting information
p. 3802 - 3805
(2014/04/03)
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- A new and convenient method for reduction of oximes to amines with NaBH3CN in the presence of MoCl5/NaHSO4? H2O system
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Various aldoximes and ketoximes were efficiently reduced to their corresponding amines with NaBH3CN in the presence of MoCl 5/NaHSO4?H2O system. Reduction reactions were carried out in refluxing EtOH or DMF within 0.3-3.8 h to afford the amines in high to excellent yields.
- Kouhkan, Mehri,Zeynizadeh, Behzad
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experimental part
p. 3323 - 3326
(2012/02/04)
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- A rapid and practical protocol for solvent-free reduction of oximes to amines with NaBH4/ZrCl4/Al2O3 system
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Solvent-free reduction of various aldoximes and ketoximes to the corresponding amines was performed easily and efficiently with NaBH4 in the presence of ZrCl4 supported on Al2O3. The reactions were carried out rapidly (within 2 min) at room temperature to afford the amines in high to excellent yields.
- Zeynizadeh, Behzad,Kouhkan, Mehri
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experimental part
p. 3448 - 3452
(2012/02/01)
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- Enantioselektive Synthese von Allyl-, Propargyl- und 4-En-2-inyl-aminen durch 1,2-Addition von Organocer-Reagenzien an chirale Aldimine
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(E)- and (Z)-Allyl-, propargyl, and 4-en-2-ynyl-amines 5 and 14, useful bifunctional building blocks and of pharmaceutical interest, are synthesized in high enantiomeric purity (e.e. >/= 97 percent).Key step is the diastereoselective 1,2-addition (d.e. 86
- Enders, Dieter,Schankat, Juergen
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p. 970 - 992
(2007/10/02)
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- Enantioselective Synthesis of Allyl- and Propargylamines via Nucleophilic 1,2-Addition to Chiral Aldimines
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The asymmetric synthesis of allylamines and propargylamines 5 in high enantiomeric purity (e.e >/= 97percent) is described.Key step is the 1,2-addition of organocerium reagents to chiral α,β-unsaturated aldimines 3 to produce secondary amines 4.The chiral
- Enders, Dieter,Schankat, Juergen
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p. 402 - 406
(2007/10/02)
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- WITTIG OLEFINATION IN THE ABSENCE OF AN EXOGENOUS BASE: A NEW SYNTHESIS OF α-SUBSTITUTED PRIMARY ALLYLIC AMINES
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A new synthesis of α-substituted primary allylic amines through the in situ generation and trapping of an ylide from the reaction of an N-acyl aziridine, triphenylphosphine, and an aldehyde in refluxing isopropanol is reported.These compounds can be prepared enantioselectively (> 94.6percent ee) by employing a chiral nonracemic N-acyl aziridine.
- Dellaria, Joseph F.,Sallin, Kevin J.
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p. 2661 - 2664
(2007/10/02)
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- Palladium(0)-Catalyzed Azidation of Allyl Esters. Selective Synthesis of Allyl Azides, Primary Allylamines, and Related Compounds
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Palladium(0)-catalyzed reaction of allyl esters such as phosphates, carbonates, and carboxylates with sodium azide gives allyl azides.The azidation proceeds with retention of configuration at the allylic carbon.Optically active (R)-(E)-(+)-4-phenyl-3-buten-2-yl azide (19) is obtained from (R)-(E)-(+)-4-phenyl-3-buten-2-yl acetate (18) stereoselectively.Sequential substitution of (Z)-4-acetoxy-2-buten-1-yl diethyl phosphate (24) with nucleophiles and subsequently azide ion gives (E)-4-substituted-2-buten-1-yl azides 27.The reaction of allyl azides with triphenylphosphine gives iminotriphenylphosphoranes, which are versatile synthetic intermediates of primary allylamines, N-allylamines, and N-allylamides.Treatment of allyl azides with triphenylphosphine and subsequently with aqueous ammonium solution gives primary allylamines.Other synthetic applications of allyl azides are also described.
- Murahashi, Shun-Ichi,Taniguchi, Yuki,Imada, Yasushi,Tanigawa, Yoshio
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p. 3292 - 3303
(2007/10/02)
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- Homogeneous Catalysis. Transition-Metal-Catalyzed Claisen Rearrangements
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Palladium(0), palladium(II), rhodium(I), and iridium(I) complexes catalyze the rearrangement of allyl imidates to allyl amides under mild conditions.The palladium(II) catalysis is characterized by exclusive regioselectivity and high steroeselectivity whereas the palladium(0), rhodium(I), and iridium(I) catalysts generally give both the and rearrangement products and although the palladium(0) catalyst can give high stereoselectivity, the rhodium(I) and iridium(I) catalysts are nonstereoselective.After a series of experiments using chiral substrates and substrates with specific deuterium labels, the mechanisms of these catalytic reactions have been elucidated.The palladium(II) catalysis is proposed to proceed via cyclic carbonium ion intermediates, and the mechanism resembles the thermal uncatalyzed Claisen rearrangement path.The palladium(0) catalysis is a form of catalytic allylation involving oxidative addition followed by nucleophilic attack on a ?-allyl intermediate.The mechansim of the rhodium(I) and iridium(I) catalysis was not as fully investigated as the others, but it appears to involve carbonium ion intermediates formed by cleavage of the allyl-oxygen bond.
- Schenck, Terry G.,Bosnich, B.
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p. 2058 - 2066
(2007/10/02)
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