Structural diversity using amino acid “Customizable Units”: conversion of hydroxyproline (Hyp) into nitrogen heterocycles

The ability of amino acid “customizable units” to generate structural diversity is illustrated by the conversion of 4-hydroxyproline (Hyp) units into a variety of nitrogen heterocycles. After a frst common step, where the unit underwent a one-pot decarboxylation–alkylation reaction to aford 2-alkylp...

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Detalles Bibliográficos
Autores: Hernández, Dácil, Porras, Marina, Boto, Alicia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/267365
Acceso en línea:http://hdl.handle.net/10261/267365
Access Level:acceso abierto
Palabra clave:Customizable units
structural diversity
N-Acyliminium ion
radical fragmentation
hydroxyproline
nitrogen heterocycles
Amino-δ-lactams
alkaloids
iminosugars
Descripción
Sumario:The ability of amino acid “customizable units” to generate structural diversity is illustrated by the conversion of 4-hydroxyproline (Hyp) units into a variety of nitrogen heterocycles. After a frst common step, where the unit underwent a one-pot decarboxylation–alkylation reaction to aford 2-alkylpyrrolidines with high stereoselectivity, a divergent step was carried out. Thus, the deprotected 4-hydroxy group was used either to initiate a radical scission that aforded aliphatic β-amino aldehydes, or to carry out an elimination reaction, to give 2-alkyl-2,5-dihydro-1H-pyrroles. In the frst case, the amines underwent a tandem reductive amination–cyclization to aford β-amino-δ-lactams, an efcient rigidifying unit in peptides. Diferent lactam N-substituents, such as alkylamines, peptides, and alkenyl chains suitable for olefn metathesis were introduced this way. In the second case, the pyrrole derivatives were efciently converted into alkaloid and iminosugar derivatives in good global yields and with excellent stereoselectivity.