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| Home > Articles > Published articles > Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes |
| Home > Articles > Published articles > Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes |
(Institut de Química Avançada de Catalunya) (Institut de Química Avançada de Catalunya) (Institut de Química Avançada de Catalunya) (Universitat Autònoma de Barcelona. Servei de Ressonància Magnètica Nuclear) (Institut de Química Avançada de Catalunya)
| Date: | 2019 |
| Abstract: | Nitrogen heterocycles are structural motifs found in many bioactive natural products and of utmost importance in pharmaceutical drug development. In this work, a stereoselective synthesis of functionalized N-heterocycles was accomplished in two steps, comprising the biocatalytic aldol addition of ethanal and simple aliphatic ketones such as propanone, butanone, 3-pentanone, cyclobutanone, and cyclopentanone to N -Cbz-protected aminoaldehydes using engineered variants of -fructose-6-phosphate aldolase from Escherichia coli (FSA) or 2-deoxy--ribose-5-phosphate aldolase from Thermotoga maritima (DERA) as catalysts. FSA catalyzed most of the additions of ketones while DERA was restricted to ethanal and propanone. Subsequent treatment with hydrogen in the presence of palladium over charcoal, yielded low-level oxygenated N-heterocyclic derivatives of piperidine, pyrrolidine and N-bicyclic structures bearing fused cyclobutane and cyclopentane rings, with stereoselectivities of 96-98 ee and 97:3 dr in isolated yields ranging from 35 to 79%. |
| Grants: | European Commission 635595 Ministerio de Economía y Competitividad CTQ2015-63563-P Ministerio de Economía y Competitividad CTQ2015-64436-P Ministerio de Ciencia e Innovación PCI2018-092937 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Biocatalysis ; Aldol reaction ; Aldolases ; Nitrogen heterocycles ; Reductive amination |
| Published in: | Advanced synthesis & catalysis, Vol. 361, Issue 11 (January 2019) , p. 2673-2687, ISSN 1615-4169 |
