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

Abstract

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.