4-(Dimethylamino)pyridine N-Oxide-Catalyzed Macrolactamization Using 2-Methyl-6-nitrobenzoic Anhydride in the Synthesis of the Depsipeptidic Analogue of FE399

Takayuki Tonoi; Takehiko Inohana; Ryo Kawahara; Teruyuki Sato; Miyuki Ikeda; Miku Akutsu; Takatsugu Murata; Isamu Shiina

doi:10.1021/acsomega.0c04878

4-(Dimethylamino)pyridine N-Oxide-Catalyzed Macrolactamization Using 2-Methyl-6-nitrobenzoic Anhydride in the Synthesis of the Depsipeptidic Analogue of FE399

ACS Omega. 2021 Jan 11;6(5):3571-3577. doi: 10.1021/acsomega.0c04878. eCollection 2021 Feb 9.

Authors

Takayuki Tonoi¹, Takehiko Inohana¹, Ryo Kawahara¹, Teruyuki Sato¹, Miyuki Ikeda¹, Miku Akutsu¹, Takatsugu Murata¹, Isamu Shiina¹

Affiliation

¹ Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.

Abstract

A depsipeptidic analogue of FE399 was efficiently synthesized mainly through macrolactamization using 2-methyl-6-nitrobenzoic anhydride (MNBA), and a detailed investigation of the desired 16-membered macrolactam core of FE399 was performed. It was determined that the combination of MNBA and a catalytic amount of 4-(dimethylamino)pyridine N-oxide exhibits much higher activity than that of conventionally used coupling reagents such as hexafluorophosphate azabenzotriazole tetramethyl uronium and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.