Development of a Triazinyluronium-Based Dehydrative Condensing Reagent with No Heteroatomic Bonds

Gaku Mizushima; Hikaru Fujita; Munetaka Kunishima

doi:10.1021/acs.joc.4c02075

Development of a Triazinyluronium-Based Dehydrative Condensing Reagent with No Heteroatomic Bonds

J Org Chem. 2024 Dec 3. doi: 10.1021/acs.joc.4c02075. Online ahead of print.

Authors

Gaku Mizushima¹, Hikaru Fujita¹, Munetaka Kunishima^{1

2}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
² Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo 650-8586, Japan.

PMID: 39626268
DOI: 10.1021/acs.joc.4c02075

Abstract

A triazinyluronium-based dehydrative condensing reagent, 2-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (DMT-TU), has been developed. Unlike commonly used guanidinium- and uronium-based reagents, DMT-TU does not contain high-energy N-N and N-O bonds, reducing its explosivity, as suggested by differential scanning calorimetry. Using DMT-TU in the presence of ⁱPr₂EtN at room temperature, carboxylic acids and amines were effectively converted to their corresponding amides. Additionally, peptide bond formation with DMT-TU exhibited suppressed racemization ratios.