- Enhanced enzymatic synthesis of the enantiopure intermediate for the blockbuster drug intermediate abacavir through a two-step enzymatic cascade reaction
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A very efficient enzymatic two-step cascade reaction was devised (E?>?200) for the resolution of activated γ-lactams (±)-1 and (±)-2. The N-hydroxymethyl group worked as a traceless activating group, when the reactions were performed with H2O (0.5?equiv) in the presence of benzylamine (1?equiv) in i-Pr2O at 60?°C. The ring-opened enantiomerically pure γ-amino acids (1S,4R)-6 (ee?=?99%, intermediate of abacavir) and (1S,3R)-8 (ee?=?99%) and unreacted lactams (1S,4R)-1 and (1R,4S)-2 (ee???96%) were obtained in good yields (?43%). Treatment of (1S,4R)-1 and (1R,4S)-2 with 18% HCl or NH4OH resulted in (1R,4S)-6·HCl and (1S,3R)-8·HCl or (1S,4R)-3 and (1R,4S)-4 quantitatively, with ee???96%.
- Galla, Zsolt,Forró, Enik?,Fül?p, Ferenc
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p. 729 - 731
(2016/08/01)
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- Identification and application of enantiocomplementary lactamases for Vince lactam derivatives
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Four enzymes showing hydrolytic activity on derivatives of 2-azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam) were successfully identified through analysis of protein crystal structure and amino acid sequence alignments. Enantiocomplementary activities were observed on Vince lactam and its saturated analog 2-azabicyclo[2.2.1]heptan-3-one with non-heme chloroperoxidase (CPO-T) from Streptomyces aureofaciens, cyclic imide hydrolase (CIH) from Pseudomonas putida, polyamidase (NfpolyA) from Nocardia farcinica, and amidase (AMI) from Rhodococcus globerulus, and perfect kinetic resolution was achieved (E>200). Computational analysis of amide bond resonance stabilization in lactams correlated well with the overall reactivity pattern of the lactams as a function of ring size and strain. The biocatalysts cloned and investigated in this study could be of interest for the synthesis of enantiopure carbocyclic nucleoside analogues.
- Assaf, Zeinab,Eger, Elisabeth,Vitnik, Zeljko,Fabian, Walter M. F.,Ribitsch, Doris,Guebitz, Georg M.,Faber, Kurt,Hall, Mélanie
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p. 2517 - 2521
(2015/04/14)
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- Enzymatic method for the synthesis of blockbuster drug intermediates - Synthesis of five-membered cyclic γ-amino acid and γ-lactam enantiomers
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A very efficient enzymatic method was developed for the synthesis of cyclic γ-lactam and γ-amino acid enantiomers, intermediates for drugs with a prominent turnover (e.g., abacavir and carbovir), through the CAL-B-catalysed enantioselective (E > 200) hydrolysis of the corresponding N-Boc protected and unprotected racemic γ-lactams with H2O in iPr2O. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Forro, Eniko,Fueloep, Ferenc
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scheme or table
p. 5263 - 5268
(2009/06/18)
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- Enantioselective synthesis of (+) and (-)-cis-3-aminocyclopentanecarboxylic acids by enzymatic asymmetrization
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Both enantiomers of cis-3-aminocyclopentanecarboxylic acid (GABA analogs, inhibitory neurotransmitter) have been prepared via enzymatic asymmetrization of cis -1,3-cyclopentanedicarboxylic acid.
- Chenevert,Martin
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p. 199 - 200
(2007/10/02)
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