Total Synthesis and Antibacterial Investigation of Plusbacin A3

Akira Katsuyama; Atmika Paudel; Suresh Panthee; Hiroshi Hamamoto; Toru Kawakami; Hironobu Hojo; Fumika Yakushiji; Satoshi Ichikawa

doi:10.1021/acs.orglett.7b01629

Total Synthesis and Antibacterial Investigation of Plusbacin A₃

Org Lett. 2017 Jul 21;19(14):3771-3774. doi: 10.1021/acs.orglett.7b01629. Epub 2017 Jul 11.

Authors

Akira Katsuyama¹, Atmika Paudel², Suresh Panthee², Hiroshi Hamamoto², Toru Kawakami³, Hironobu Hojo³, Fumika Yakushiji^{1

4}, Satoshi Ichikawa^{1

4}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
² Institute of Medical Mycology, Teikyo University , 359 Otsuka, Hachioji, Tokyo 192-0395, Japan.
³ Institute for Protein Research, Osaka University , 3-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
⁴ Center for Research and Education on Drug Discovery, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

PMID: 28696114
DOI: 10.1021/acs.orglett.7b01629

Abstract

The total synthesis of plusbacin A₃ (1) has been accomplished using a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) as a key step. Two trans-3-hydroxy-l-proline residues were constructed by combining the JU-3CR with a convertible isocyanide strategy. Subsequent peptide coupling and macrolactamization afforded plusbacin A₃. Investigating the antibacterial activity of 1 compared with that of its dideoxy analogue revealed that the threo-β-hydroxyaspartic acid residues are essential for antibacterial activity. Notably, there is a low potential for the development of resistance in S. aureus against plusbacin A₃.

Publication types

Research Support, Non-U.S. Gov't