L-Rhamnulose-1-phosphate and L-fuculose-1-phosphate aldolase mediated multi-enzyme cascade systems for nitrocyclitol synthesis

One-pot multistep stereoselective cascade reactions were implemented for the straightforward synthe-sis of various nitrocyclitols. Two kinases, an aldolase and a phosphatase were involved in this process,together with a spontaneous intramolecular Henry reaction to provide the nitrocyclitol moiety. T...

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Detalles Bibliográficos
Autores: Camps Bres, Flora, Guérard-Hélaine, Christine, Hélaine, Virgil, Fernandes, Carlos, Sánchez-Moreno, Israel, Traïkia, Mounir, García-Junceda, Eduardo, Lemaire, Marielle
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/113487
Acceso en línea:http://hdl.handle.net/10261/113487
Access Level:acceso abierto
Palabra clave:Nitrocyclitol
Aldolase
Biocatalysis
Henry reaction
Cascade processes
Descripción
Sumario:One-pot multistep stereoselective cascade reactions were implemented for the straightforward synthe-sis of various nitrocyclitols. Two kinases, an aldolase and a phosphatase were involved in this process,together with a spontaneous intramolecular Henry reaction to provide the nitrocyclitol moiety. The C Cbond formation catalysed by the aldolase and the nitroaldol reactions were key steps to build the carbocy-cle stereoselectively. The aldolase acceptor substrates were all 4-nitrobutanal structurally based, eitherhydroxylated or unsubstituted at the C2 and/or C3 positions. l-Fuculose-1-phosphate aldolase (FucA)catalysed the formation of the expected (R,R)- or d-erythro aldol, except in the case of 4-nitrobutanal,from which the epimeric (R,S)- or l-threo aldol was also formed. l-Rhamnulose-1-phosphate aldolase con-sistently formed the expected (R,S)- or l-threo aldol together with a minor amount of (R,R)- or d-erythroaldol. The intramolecular Henry reaction was also found to be stereoselective, occurring spontaneouslyonce the aldol was formed due to the presence of both ketone and a terminally positioned nitro group.The combination of this set of reactions successfully furnished 11 nitrocyclitols which have not beendescribed previously in the literature.