Heterocycles 36. Single-Walled Carbon Nanotubes-Bound N,N-Diethyl Ethanolamine as Mild and Efficient Racemisation Agent in the Enzymatic DKR of 2-Arylthiazol-4-yl-alanines (original) (raw)
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Tetrahedron: Asymmetry, 2010
The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a-d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a-d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g**)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a-d, four possible tetrahedral intermediate states were compared and analyzed.
Lipase-catalyzed kinetic resolution of racemic 1-heteroarylethanols—experimental and QM/MM study
Tetrahedron-asymmetry, 2008
The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a–d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a–d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g∗∗)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a–d, four possible tetrahedral intermediate states were compared and analyzed.(S)-1-(Benzo[d]thiazol-2-yl)ethanolC9H9NOSEe = 97% (by GC analysis)[α]D25=-18.4 (c 1.0, CHCl3)Source of chirality: lipase-catalyzed kinetic resolutionAbsolute configuration: (S)(S)-1-(Benzo[b]thiophen-2-yl)ethanolC10H10OSEe = 99% (by GC analysis)[α]D25=-21.2 (c 1.0, CHCl3)Source of chirality: lipase-catalyzed kinetic resolutionAbsolute configuration: (S)
Synthetic Communications, 1998
The kinetic resolution of racemic 1-(benzothiazol-2-yl)ethanol rac-2a, 1-(benzo[b]thiophen-2-yl)ethanol rac-2b, 1-(benzo[b]furan-3-yl)ethanol rac-2c and 1-(benzo[b]thiophen-3-yl)ethanol rac-2d was studied by enantiomer selective acylation catalyzed by a selection of commercially available and in house produced lipases. Alcoholysis of the corresponding racemic acetates rac-3a-d catalyzed by Candida antarctica lipase B (CaLB) was also investigated. Two racemic 1-heteroarylethanols rac-2a,b were prepared by addition of the corresponding lithiated heteroarylic compounds 1a,b to acetaldehyde, whereas two others, rac-2c,d were synthesized by the addition of MeMgI onto the corresponding heteroaryl-carbaldehydes 1c,d. The high enantiomer selectivities of CaLB in the acylation of racemic 1-heteroarylethanols rac-2a-d allowed the determination of the enantiomeric preference of these enzymatic acetylation reactions by QM/MM [pm3/uff or hf(3-21+g**)/uff] calculations. For acetylation of each of the racemic alcohols rac-2a-d, four possible tetrahedral intermediate states were compared and analyzed.
Journal of Molecular Catalysis B: Enzymatic, 2006
Five novel methyl (±)-2-(2-acetoxyethyl)-4-arylmethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylates have been synthesized and their lipase-catalyzed resolution via stereoselective deacetylation of acetoxyethyl moiety present in the molecule studied. It has been observed that Novozyme ®-435 in THF efficiently catalyses the enantioselective deacetylation of these acetoxyethyl dihydrobenzoxazines leading to the formation of optically enriched methyl (+)-4-arylmethyl-2-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylates. The biocatalytic reaction was found to be chemoselective alongwith being enantioselective, because the lipase exclusively catalyses the deesterification of the ester function derived from the alcoholic hydroxy moiety in the molecule over the one derived from the aromatic carboxylic acid group.
Preparation of enantiomerically pure N-heterocyclic amino alcohols by enzymatic kinetic resolution
Tetrahedron: Asymmetry, 2015
The synthesis of both enantiomers of N-benzyl-3-hydroxypyrrolidine and N-benzyl-3-hydroxypiperidine via enzymatic kinetic resolution of the corresponding racemic esters is described. Various commercially available hydrolases were studied as biocatalysts in native and immobilized form. The best results were obtained with lipases PS, AK, CAL-B and with protease Alcalase, which were active and selective for the kinetic resolutions of racemic esters (E > 100). Under optimized reaction conditions, highly enantiomerically enriched (up to 99.5% ee) resolution products were obtained. Lipase and protease showed opposite enantiopreference on the esters, allowing the preparation of both enantiomers of the target compounds. Semi-continuous reactions in column reactors with immobilized biocatalysts were also performed with high enantioselectivities. Inversion of the configuration at C(3) of N-benzyl-3-hydroxypyrrolidine was quantitatively effected in a short number of steps.
Tetrahedron-asymmetry, 2010
The synthesis of both enantiomers of 1-(10-ethyl-10H-phenothiazin-1,2, and 4-yl)ethanols 1a–c and their acetates via enantioselective methanolysis of the corresponding racemic esters rac2a–c with lipase B from Candida antarctica (CaL-B) or/and by acylation of the racemic alcohols with the lipase A or lipase B from C. antarctica (CaL-A and CaL-B) is described. The absolute configuration of enantiopure 1-(10-ethyl-10H-phenothiazin-1-yl)ethyl acetate 2a was assigned as (R) by using QM/MM(hf/3–21g:uff) calculations within the CaL-B (1LBT crystal structure) enzymic environment.(R)-1-(10-ethyl-10H-phenothiazin-1-yl)ethanolC16H17NOSEe >99% on LiChroCART (R,R)-Whelk-O1 column HPLC column[α]D25=+14.8 (c 1.0, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)(R)-1-(10-ethyl-10H-phenothiazin-2-yl)ethanolC16H17NOSEe >99% on Chiralpak IB HPLC column[α]D25=+46.4 (c 1.0, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)(R)-1-(10-ethyl-10H-phenothiazin-4-yl)ethanolC16H17NOSEe >99% on Chiralpak IC HPLC column[α]D25=+145.3 (c 1.0, CHCl3)Source of chirality: enzymatic reactionAbsolute configuration: (R)
The Journal of Organic Chemistry, 2009
A one-pot sequential process, involving a radical racemization and an enzymatic resolution, provides access to (S)amides, from racemic amines, with ee and yields ranging from 78 to 94% and 58 to 80%, respectively. Dynamic kinetic resolution (DKR) of racemic amines enables their conversion into enantiomerically pure amides. 1 Our group 2 and others 3,4 have recently reported (R)-selective chemoenzy-matic DKR of amines. In most cases, racemization was based on metal-catalyzed reversible dehydrogenation of the amine into the corresponding imine. Our approach was different since the racemization process relied on reversible hydrogen atom abstraction at the stereocenter (directly adjacent to the reactive amine moiety) by sulfanyl radical. 5,6 The known examples of (S)-selective chemoenzymatic DKRs involving hydrolases refer exclusively to alcohols. 7 We report herein chemoenzymatic conversion of aliphatic amines into the corresponding (S)-amides through a one-pot three-step sequence (Scheme 1).
Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors
Tetrahedron: Asymmetry, 2017
The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-β-lactamase inhibitors is described. The reaction of β-aminoalcohols and 2,5-dihydroxy-1,4-dithiane led to oxazolidinylthiazolidines and/or dithia-azabicycles as the main products. The distribution pattern depends mainly on the aminoalcohol substituents. In a one-pot reaction, four new bonds are formed in good yields and with high atom efficiency. When the oxazolidinylthiazolidines are formed, two stereogenic centres are generated with high enantiospecificity. The reaction mechanism is discussed based on crystallographic data and interconversion studies. Two oxazolidinylthiazolidines were evaluated as inhibitors of the potent lactamase NDM-1 and compound 4f displayed competitive inhibition with K i = 1.6 ± 0.6 µM.
Journal of Molecular Catalysis B: Enzymatic, 2014
The synthesis of both enantiomers of four new phenylthiazole-based amines by enantiomer-selective acylation of racemic amines and by hydrolysis of the corresponding racemic amides using lipase B from Candida antarctica (Novozyme 435) as chiral catalyst was performed with good yields and excellent enantioselectivities. In order to prevent the frequently occurring partial racemization of enantiopure amides during chemical hydrolysis to the corresponding (R)-amines, the deprotection of the N-acylated (R)-enantiomers by mild enzymatic hydrolysis with lipase A from C. antarctica immobilized on Celite was also developed.