Brønsted Acid-Catalyzed Epimerization-Free Preparation of Dual-Protected Amino Acid Derivatives

Pedro P de Castro; Isabela M R Rimulo; Angelina M de Almeida; Renata Diniz; Giovanni W Amarante

doi:10.1021/acsomega.7b00523

Brønsted Acid-Catalyzed Epimerization-Free Preparation of Dual-Protected Amino Acid Derivatives

ACS Omega. 2017 Jun 27;2(6):2967-2976. doi: 10.1021/acsomega.7b00523. eCollection 2017 Jun 30.

Authors

Pedro P de Castro¹, Isabela M R Rimulo¹, Angelina M de Almeida¹, Renata Diniz², Giovanni W Amarante¹

Affiliations

¹ Department of Chemistry, Federal University of Juiz de Fora, Campus Martelos, Juiz de Fora, Minas Gerais 36036-900, Brazil.
² Department of Chemistry, Federal University of Minas Gerais, Campus Pampulha, Belo Horizonte, Minas Gerais 31270-901, Brazil.

Abstract

An organocatalytic protocol, employing the commercially available EDC as coupling agent, has been developed for the preparation of dual-protected amino acid derivatives without epimerization. This methodology was then applied to different Boc-amino acid and amine derivatives in moderate to excellent isolated yields. In addition, racemization-free Boc deprotection was also demonstrated. Mechanism investigation through electrospray ionization (+)-mass spectrometry/mass spectrometry revealed an acyclic intermediate (no azlactone formation) activated by the camphorsulfonic acid as an organocatalyst as a key step for the sequential attack of the nucleophile.