A New Tetracyclic Bromopyrrole-Imidazole Derivative through Direct Chemical Diversification of Substances Present in Natural Product Extract from Marine Sponge Petrosia (Strongylophora) sp

Natchanun Sirimangkalakitti; Kazuo Harada; Makito Yamada; Masayoshi Arai; Mitsuhiro Arisawa

doi:10.3390/molecules28010143

A New Tetracyclic Bromopyrrole-Imidazole Derivative through Direct Chemical Diversification of Substances Present in Natural Product Extract from Marine Sponge Petrosia (Strongylophora) sp

Molecules. 2022 Dec 24;28(1):143. doi: 10.3390/molecules28010143.

Authors

Natchanun Sirimangkalakitti¹, Kazuo Harada¹, Makito Yamada¹, Masayoshi Arai¹, Mitsuhiro Arisawa¹

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Osaka, Japan.

Abstract

Chemical diversification of substances present in natural product extracts can lead to a number of natural product-like compounds with a better chance of desirable bioactivities. The aim of this work was to discover unprecedented chemical conversion and produce new compounds through a one-step reaction of substances present in the extracts of marine sponges. In this report, a new unnatural tetracyclic bromopyrrole-imidazole derivative, rac-6-OEt-cylindradine A (1), was created from a chemically diversified extract of the sponge Petrosia (Strongylophora) sp. We also confirmed that 1 originated from naturally occurring (-)-cylindradine A (2) via a new reaction pattern. Moreover, (-)-dibromophakellin (3) and 4,5-dibromopyrrole-2-carboxylic acid (4), as well as 2, were reported herein for the first time in this genus. Studies on the possible reaction mechanism and bioactivities were also conducted. The results indicate that the direct chemical diversification of substances present in natural product extracts can be a speedy and useful strategy for the discovery of new compounds.

Keywords: bromopyrrole imidazole alkaloid; chemical diversification; cylindradines; marine sponge Petrosia (Strongylophora) sp.; natural product extract; natural product-like compound; one-step reaction.

MeSH terms

Animals
Imidazoles
Petrosia* / chemistry
Porifera* / chemistry

Substances

Imidazoles

Grants and funding

This research was funded by The Tokyo Biochemical Research Foundation, ID No. TBRF-RF19-116 and JSPS KAKENHI, Grant No. JP22K15252 to N.S. The authors express their gratitude for partial support by Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED, Grant No. JP21am0101085 and JP22ama121054 to N.S., M.A. (Masayoshi Arai), and M.A. (Mitsuhiro Arisawa), and JSPS KAKENHI, Grant No. 21H02069 to M.A. (Masayoshi Arai). The authors also wish to thank the Kobayashi Foundation for financial assistance to N.S. and M.A. (Mitsuhiro Arisawa).