Radical Functionalization of Unsaturated Amino Acids: Synthesis of Side-Chain-Fluorinated, Azido-Substituted, and Hydroxylated Amino Acids

Philip A P Reeve; Urszula Grabowska; Lourdes Salvador Oden; Daniel Wiktelius; Fredrik Wångsell; Richard F W Jackson

doi:10.1021/acsomega.9b01509

Radical Functionalization of Unsaturated Amino Acids: Synthesis of Side-Chain-Fluorinated, Azido-Substituted, and Hydroxylated Amino Acids

ACS Omega. 2019 Jun 21;4(6):10854-10865. doi: 10.1021/acsomega.9b01509. eCollection 2019 Jun 30.

Authors

Philip A P Reeve¹, Urszula Grabowska², Lourdes Salvador Oden², Daniel Wiktelius², Fredrik Wångsell², Richard F W Jackson¹

Affiliations

¹ Department of Chemistry, The University of Sheffield, Dainton Building, Sheffield S3 7HF, U.K.
² Medivir AB, P.O. Box 1086, SE-141 22 Huddinge, Sweden.

Abstract

A range of enantiomerically pure protected side-chain-fluorinated amino acids has been prepared (13 examples) by treatment of protected amino acids containing unsaturated side chains with a combination of Fe(III)/NaBH₄ and Selectfluor. The modification of the conditions by replacement of Selectfluor with NaN₃ allowed the preparation of side-chain azido-substituted amino acids (five examples), which upon catalytic hydrogenation gave the corresponding amines, isolated as lactams (four examples). Radical hydration of the unsaturated side chains leading to side-chain-hydroxylated protected amino acids has also been demonstrated.