Benzimidazolinone-Free Peptide o‑Aminoanilides for Chemical Protein Synthesis

• Published in: Organic letters Vol. 21; no. 22; pp. 9040 - 9044
• Main Authors: Mannuthodikayil, Jamsad, Singh, Sameer, Biswas, Anamika, Kar, Abhisek, Tabassum, Wahida, Vydyam, Pratap, Bhattacharyya, Mrinal Kanti, Mandal, Kalyaneswar
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-11-2019
• Subjects: Anilides - chemistry; Benzimidazoles; Peptides - chemistry; Protozoan Proteins - chemical synthesis; Ubiquitin - chemical synthesis
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.9b03440

The thioester surrogate 3,4-diaminobenzoic acid (Dbz) facilitates the efficient synthesis of peptide thioesters by Fmoc chemistry solid phase peptide synthesis and the optional attachment of a solubility tag at the C-terminus. The protection of the partially deactivated ortho-amine of Dbz is necessary to obtain contamination-free peptide synthesis. The reported carbamate protecting groups promote a serious side reaction, benzimidazolinone formation. Herein we introduce the Boc-protected Dbz that prevents the benzimidazolinone formation, leading to clean peptide o-aminoanilides suitable for the total chemical synthesis of proteins.