pKa Modulation of Pyrrolidine-Based Catalytic Polymers Used for the Preparation of Glycosyl Hydrazides at Physiological pH and Temperature

Inspired by the ability of enzymes to use the surrounding hydrophobic and/or polarizable groups to modulate the pK of a given amino acid, we designed a series of soluble polymers able to decrease the basicity of pyrrolidine (from 11.2 to 8.6 pK units), which clearly increases its aminocatalytic acti...

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Detalles Bibliográficos
Autores: Vargas, E. L., Velázquez, J. A., Rodrigo, Eduardo, Reinecke, Helmut, Rodríguez-Hernández, Juan, Fernández-Mayoralas, Alfonso, Gallardo Ruiz, Alberto, Cid, M. Belén
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/217563
Acceso en línea:http://hdl.handle.net/10261/217563
Access Level:acceso abierto
Palabra clave:Enzyme-like organocatalysis
Iminium activation
Pyrrolidine
pKa modulation
Polymers
Hydrazones
Descripción
Sumario:Inspired by the ability of enzymes to use the surrounding hydrophobic and/or polarizable groups to modulate the pK of a given amino acid, we designed a series of soluble polymers able to decrease the basicity of pyrrolidine (from 11.2 to 8.6 pK units), which clearly increases its aminocatalytic activity at physiological pH in C═N bond formation reactions via ion iminium activation. Other parameters such as charge density, hydrophobic/hydrophilic balance, and aggregation state have been studied as important factors in the catalytic activity of the polymers for a given substrate. To demonstrate the utility of our approach, an optimal pyrrolidine-based catalytic polymer has been used for the formation of C-N bonds between hydrazides and free sugars as the model system for the preparation of glycoconjugates.