- Biocatalysis for the preparation of optically active β-lactam precursors of amino acids
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Enantioselective acylation of N-hydroxymethylated β-lactams in the presence of Pseudomonas sp. lipase afforded optically active precursors for the preparation of (1R,2S)- and (1S,2R)-2-aminocyclopentane- and (1R,2S,3R,4S)- and (1S,2R,3S,4R)-3-aminobicyclo[2.2.1]heptanecarboxylic acids. Due to the high enantioselectivity (E = 90 and 62) and in order to minimize the enzymatic hydrolysis of the acylated products back to the starting alcohol, the reactions were performed in acetone.
- Csomos, Peter,Kanerva, Liisa T.,Bernath, Gabor,Fueloep, Ferenc
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Read Online
- The N-Hydroxymethyl Group as a Traceless Activating Group for the CAL-B-Catalysed Ring Cleavage of β-Lactams: A Type of Two-Step Cascade Reaction
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An efficient enzymatic two-step cascade procedure has been devised for rapid access to diverse amino acids from N-hydroxymethyl-β-lactams; representative amino acids include the antifungal agent cispentacin, intermediates for the taxol side-chain, and assorted cathepsin inhibitors. When CAL-B-catalysed hydrolyses of racemic N-hydroxymethyl-β-lactams were performed with H2O (0.5 equiv.) in iPr2O at 60 °C, relatively quick (vs. non-activated counterparts) and enantioselective (E > 200) ring cleavage reactions took place. As the ring-opened amino acids formed, the hydroxymethyl group, as a traceless activating group, underwent spontaneous in situ degradation. Consequently, the desired β-amino acid and unreacted N-hydroxymethyl-β-lactam enantiomers (ee > 95 %) were formed. The formation of polymers, induced by liberation of formaldehyde, was successfully restricted by the addition of benzylamine as a capture agent, to the enzymatic reactions. An efficient enzymatic two-step cascade procedure was devised for CAL-B-catalysed hydrolysis of racemic N-hydroxymethyl-β-lactams. Conditions in which the hydroxymethyl group serves as a traceless activating group (E > 200), giving desired β-amino acid along with unreacted starting lactam enantiomers (ee > 95 %) were identified; polymerization was controlled by addition benzylamine addition.
- Forró, Enik?,Galla, Zsolt,Fül?p, Ferenc
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p. 2647 - 2652
(2016/06/09)
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- Solid-phase synthesis of 6,7-cycloalkane-fused 1,4-diazepane-2,5-diones via a cyclization/release strategy
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A solid-phase synthesis procedure for the parallel preparation of 6,7-cycloalkane-fused 1,4-diazepane-2,5-diones is described. The methodology applies α- and alicyclic β-amino acid building blocks to construct the seven-membered heterocyclic core, while a
- Caroen, Jurgen,Clemmen, An,Kámán, Judit,Backaert, Fréderique,Goeman, Jan L.,Fül?p, Ferenc,Van Der Eycken, Johan
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p. 148 - 160
(2015/12/23)
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- Hairpin folding behavior of mixed α/β-peptides in aqueous solution
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The invention of new strategies for the design of protein-mimetic oligomers that manifest the folding encoded in natural amino acid sequences is a significant challenge. In contrast to the α-helix, mimicry of protein β-sheets is less understood. We report
- Lengyel, George A.,Frank, Rebecca C.,Horne, W. Seth
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p. 4246 - 4249
(2011/06/21)
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- New compounds
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The present invention encompasses compounds of general formula (1) wherein R1, R2, R4, X, m, n and p are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.
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Page/Page column 9
(2009/07/10)
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- NEW COMPOUNDS
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The present invention encompassescompounds of general formula (1) wherein R1 to R4 , X and n are defined as in claim 1, which are suitable for the treatment of ailments characterised byexcessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
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Page/Page column 18
(2008/12/06)
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- Development of a suitable process for the preparation of a TNF-α converting enzyme inhibitor, WAY-281418
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A suitable process for the preparation of kilogram quantities of a TNF-α converting enzyme (TACE) inhibitor (WAY-281418) was developed using isatin 13 as starting material and an efficient coupling step for the formation of sulfonamide 8 in a 15% overall yield. Process preparation of (+)-(1S,2R)-2-aminocyclopentane-1-carboxylic acid (7, (+)-cispentacin), a chiral component for WAY-281418, was successfully scaled up via an asymmetric hydroge-nation reaction. Crystallization allowed the isolation of all intermediates and the final product 9.
- Wang, Youchu,Papamichelakis, Maria,Chew, Warren,Sellstedt, John,Noureldin, Razzak,Tadayon, Sam,Daigneault, Sylvain,Galante, Rocco J.,Sun, Jerry
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p. 1253 - 1260
(2013/01/03)
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- The first direct enzymatic hydrolysis of alicyclic β-amino esters: A route to enantiopure cis and trans β-amino acids
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The first direct enzymatic method is reported for the synthesis of cis and trans βamino acid enantiomers through the lipase-catalyzed enantioselective hydrolysis of alicyclic β esters in organic media. High enantioselectivities (E usually > 001) were observed when the Candida antarctica lipase B catalyzed reactions were performed with H2O (0.5 equivalents) in iP iPr2O at 5°C. The resolved products, obtained in good yields (≥42%), could be easily separated.
- Forro, Eniko,Fueloep, Ferenc
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p. 6397 - 6401
(2008/02/13)
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- 2,4-diamino-pyrimidines as aurora inhibitors
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The present invention encompasses compounds of general formula (1) wherein R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a pharmaceutical composition having the above-mentioned properties.
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Page/Page column 18
(2008/06/13)
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- Self-condensation of N-tert-butanesulfinyl aldimines: Application to the rapid asymmetric synthesis of biologically important amine-containing compounds
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(Chemical Equation Presented) Highly diastereoselective intra- and intermolecular self-condensation reactions of N-tert-butanesulfinyl aldimines have been developed and applied to the rapid, asymmetric synthesis of frans-2-aminocyclopentanecarboxylic acid and the drug candidate SC-53116. Key to both syntheses is a novel microwave-assisted reaction in which N-sulfinyl aldimines are cleanly converted into nitrites in high-yielding concerted elimination processes.
- Schenkel, Laurie B.,Ellman, Jonathan A.
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p. 3621 - 3624
(2007/10/03)
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- Lipase-catalyzed enantioselective ring opening of unactivated alicyclic-fused beta-lactams in an organic solvent.
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[reaction: see text] A highly efficient and very simple method was developed for the synthesis of enantiopure beta-amino acids (e.g. cispentacin) and beta-lactams through the enzyme-catalyzed enantioselective ring opening of unactivated alicyclic beta-lac
- Forro, Eniko,Fueloep, Ferenc
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p. 1209 - 1212
(2007/10/03)
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- A stereoselective synthesis of five- and six-membered cyclic β-amino acids
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The cyclic β-amino acids 1 and 2 have been prepared in a short and stereoselective manner. The synthesis features a diastereoselective thioester enolate/imine condensation reaction and a ring-closing metathesis as key processes. Wiley-VCH Verlag GmbH & Co
- Perlmutter, Patrick,Rose, Mark,Vounatsos, Filisaty
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p. 756 - 760
(2007/10/03)
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- Asymmetric synthesis of cyclic β-amino acids and cyclic amines via sequential diastereoselective conjugate addition and ring closing metathesis
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Diastereoselective conjugate addition of lithium (S)-N-allyl-N-α-methylbenzylamide to a range of α,β-unsaturated esters followed by ring closing metathesis is used to afford efficiently a range of substituted cyclic β-amino esters in high d.e. Alternatively, conjugate addition to α,β-unsaturated Weinreb amides, functional group conversion and ring closing metathesis affords cyclic amines in high d.e. The further application of this methodology to the synthesis of a range of carbocyclic β-amino esters via conjugate addition, enolate alkylation and ring closing metathesis is also described. Application of this methodology affords, after deprotection, (S)-homoproline, (S)-homopipecolic acid, (S)-coniine and (1S,2S)-trans-pentacin.
- Chippindale, Ann M.,Davies, Stephen G.,Iwamoto, Keiji,Parkin, Richard M.,Smethurst, Christian A. P.,Smith, Andrew D.,Rodriguez-Solla, Humberto
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p. 3253 - 3265
(2007/10/03)
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- Efficient asymmetric synthesis of unnatural β-amino acids
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The simple and highly enantioselective methanolysis of cyclic meso-anhydrides mediated by cinchona alkaloids leads to a broad variety of dicarboxylic acid mono-methyl esters with up to 99% ee. From these products, unnatural N-protected β-amino esters can be obtained by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of the protecting groups leads to the free β-amino acids in excellent yields. By enantiomer differentiating opening of racemic anhydrides, synthetically highly useful regioisomeric amino acid esters become readily available.
- Bolm,Schiffers,Dinter,Defrere,Gerlach,Raabe
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p. 1719 - 1730
(2007/10/03)
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- Large-scale syntheses of FMOC-protected non-proteogenic amino acids: Useful building blocks for combinatorial libraries
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Convenient and reliable large-scale procedures for the protection of various amino acids with N-(9-fluorenylmethoxycarbonyl)oxysuccinimide (FMOC-OSu) are described. Commercially available 4-aminomethylbenzoic acid and trans-4-(aminomethyl)cyclohexanecarbo
- Dener, Jeffrey M.,Fantauzzi, Pascal P.,Kshirsagar, Tushar A.,Kelly, Daphne E.,Wolfe, Aaron B.
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p. 445 - 449
(2013/09/07)
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- Asymmetric Synthesis of (-)-(1R,2S)-Cispentacin and Related cis- and trans-2-Amino Cyclopentane- and Cyclohexane-1-carboxylic Acids
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The antifungal antibiotic (-)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid (cispentacin) 8 and its cyclohexane homologue 14 have been prepared utilizing the highly stereoselective conjugate addition of homochiral lithium N-benzyl-N-α-methylbenzylamide 5.
- Davies, Stephen G.,Ichihara, Osamu,Lenoir, Isabelle,Walters, Iain A. S.
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p. 1411 - 1416
(2007/10/02)
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