Polyhydroxylated Cyclopentane β-Amino Acids Derived from d-Mannose and d-Galactose: Synthesis and Protocol for Incorporation into Peptides

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises, as key steps, ring-closing metathesis of a polysubstituted diene intermediate followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1-ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected d-mannose and d-galactose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported.This work has received financial support from the European Union (European Regional Development Fund - ERDF), the Spanish Ministerio de Economía y Competitividad (SAF2014-60138-R), the CIBER BBN (CB/06/01/0074), the Xunta de Galicia (Centro Singular de Investigación de Galicia accreditation 2019–2022, ED431G 2019/03; and grants ED431C 2018/30 and ED431C 2018/04), the Generalitat de Catalunya (2017-SGR-1439), and the Galchimia S.A. (Spain). R.B. and F.F. thank the Ministerio de Educación, Cultura y Deporte and the Ministerio de Educación y Ciencia, respectively, for FPU fellowships.Peer reviewe