TY - JOUR
T1 - Aldolase-Catalyzed Asymmetric Synthesis of N-Heterocycles by Addition of Simple Aliphatic Nucleophiles to Aminoaldehydes
AU - Roldán, Raquel
AU - Hernández, Karel
AU - Joglar, Jesús
AU - Bujons, Jordi
AU - Parella, Teodor
AU - Fessner, Wolf Dieter
AU - Clapés, Pere
N1 - Publisher Copyright:
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
PY - 2019/6/6
Y1 - 2019/6/6
N2 - 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.).
AB - 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.).
KW - Aldol reaction
KW - Aldolases
KW - Biocatalysis
KW - Nitrogen heterocycles
KW - Reductive amination
UR - http://www.scopus.com/inward/record.url?scp=85061638556&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000471070400032&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1002/adsc.201801530
DO - 10.1002/adsc.201801530
M3 - Article
C2 - 31680790
AN - SCOPUS:85061638556
SN - 1615-4150
VL - 361
SP - 2673
EP - 2687
JO - Advanced Synthesis and Catalysis
JF - Advanced Synthesis and Catalysis
IS - 11
ER -