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-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.This work was partly financed by projects RETOS-SELECTFIGHT (PID2020-116688RB-C21) and CTQ2006-14260/PPQ of the Plan Nacional I+D, Ministry of Science, Spain (with FEDER funds). We also thank Project APOGEO (Cooperation Program INTERREG-MAC 2014–2020, with European Funds for Regional Development-FEDER) and by project ProID2020010134 (Programa de Subvenciones a la Realización I+D “Mª Carmen Betancourt y Molina from ACIISI-Gobierno de Canarias with FEDER funds). D.H. also acknowledges her current contract (TRANSALUDAGRO) financed by Cabildo de Tenerife, Program TF INNOVA 2016-21 (with MEDI & FDCAN Funds). M.P. thanks predoctoral grants from Gobierno de Canarias (Convocatoria Tesis 2020) and Ministerio de Ciencia, Innovación y Universidades, Spain (FPU grants). We also acknowledge support of the publication fee by CSIC Open Access Publication Support Initiative-through its Unit of Information Resources for Research (URICI).Peer reviewe