Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes

Raquel Roldán, Karel Hernández, Jesús Joglar, Jordi Bujons, Teodor Parella, Wolf Dieter Fessner, Pere Clapés*

*Autor corresponent d’aquest treball

Producció científica: Article en revista indexadaArticleAvaluat per experts

20 Cites (Scopus)

Resum

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 d-fructose-6-phosphate aldolase from Escherichia coli (FSA) or 2-deoxy-d-ribose-5-phosphate aldolase from Thermotoga maritima (DERATma) as catalysts. FSA catalyzed most of the additions of ketones while DERATma 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%. (Figure presented.).

Idioma originalAnglès
Pàgines (de-a)2673-2687
Nombre de pàgines15
RevistaAdvanced Synthesis and Catalysis
Volum361
Número11
DOIs
Estat de la publicacióPublicada - 6 de juny 2019
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