Solid-Phase Total Synthesis of Plusbacin A3

Kazuki Takashina; Akira Katsuyama; Rintaro Kaguchi; Kazuki Yamamoto; Toyotaka Sato; Satoshi Takahashi; Motohiro Horiuchi; Shin-Ichi Yokota; Satoshi Ichikawa

doi:10.1021/acs.orglett.2c00667

Solid-Phase Total Synthesis of Plusbacin A₃

Org Lett. 2022 Mar 25;24(11):2253-2257. doi: 10.1021/acs.orglett.2c00667. Epub 2022 Mar 16.

Authors

Kazuki Takashina¹, Akira Katsuyama^{1

2

3}, Rintaro Kaguchi¹, Kazuki Yamamoto^{1

2}, Toyotaka Sato^{4

5}, Satoshi Takahashi^{6

7}, Motohiro Horiuchi^{4

5}, Shin-Ichi Yokota⁸, Satoshi Ichikawa^{1

2

3}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
² Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
³ Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
⁴ Faculty of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
⁵ Graduate School of Infectious Diseases, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
⁶ Division of Laboratory Medicine, Sapporo Medical University Hospital, Minami-1, Nishi-16, Chuo-ku, Sapporo 060-8543, Japan.
⁷ Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Minami-1, Nishi-16, Chuo-ku, Sapporo 060-8543, Japan.
⁸ Department of Microbiology, Sapporo Medical University School of Medicine, Minami-1, Nishi-17, Chuo-ku, Sapporo 060-8556, Japan.

PMID: 35293208
DOI: 10.1021/acs.orglett.2c00667

Abstract

The total synthesis of the depsipeptide natural product plusbacin A₃ (1) utilizing solid-phase peptide synthesis (SPPS) was disclosed. A 3-hydroxy-proline derivative compatible with Fmoc SPPS was prepared by a diastereoselective Joullié-Ugi three-component reaction (JU-3CR)/hydrolysis sequence. After peptide elongation on the solid support, cleavage of the peptide from the resin, followed by macrolactamization and global deprotection, gave plusbacin A₃ (1).

Publication types

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

MeSH terms

Depsipeptides*
Hydrolysis
Solid-Phase Synthesis Techniques*

Substances

Depsipeptides
plusbacin A3