One-Step Synthesis of 3-(Fmoc-amino acid)-3,4-diaminobenzoic Acids

Min-Cheng Chien; Yi Kai Lin; Yong Liao; Szu-Hsuan Chen; Yen-Wei Chen; Chien-Yu Liang; Vijayasimha Molakaseema; Sodio C N Hsu; Chun-Cheng Lin; Hui-Ting Chen; Chai-Lin Kao

doi:10.1021/acsomega.3c06640

One-Step Synthesis of 3-(Fmoc-amino acid)-3,4-diaminobenzoic Acids

ACS Omega. 2023 Oct 24;8(44):41855-41864. doi: 10.1021/acsomega.3c06640. eCollection 2023 Nov 7.

Authors

Min-Cheng Chien¹, Yi Kai Lin¹, Yong Liao², Szu-Hsuan Chen¹, Yen-Wei Chen¹, Chien-Yu Liang¹, Vijayasimha Molakaseema¹, Sodio C N Hsu¹, Chun-Cheng Lin^{1

3}, Hui-Ting Chen², Chai-Lin Kao^{1

4

5

6

7}

Affiliations

¹ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
³ Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan.
⁴ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁵ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁶ Department of Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
⁷ College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.

Abstract

A one-step method for synthesizing 3-(Fmoc-amino acid)-3,4-diaminobenzoic acids was used to prepare preloaded diaminobenzoate resin. The coupling of free diaminobenzoic acid and Fmoc-amino acids gave pure products in 40-94% yield without any purification step in addition to precipitation except for histidine. For the proline residue, crude products were collected and used for solid-phase peptide synthesis to give a moderate yield of a pentapeptide. In addition, this method was used to prepare unusual amino acid derivatives, namely, (2-naphthyl) alanine and 6-aminohexanoic acid derivatives, in 50 and 65% yield, respectively.