Structure Elucidation of Calyxoside B, a Bipolar Sphingolipid from a Marine Sponge Cladocroce sp. through the Use of Beckmann Rearrangement.

Kenji Sugawara,Yuji Ise,Nobuhiro Yamawaki,Shigeru Okada,Hisayoshi Yokose,Hiroshi Watarai,Shigeki Matsunaga,Yasuhiro Morii

doi:10.3390/md19060287

Abstract

Marine sponges are an excellent source of biologically active secondary metabolites. We focus on deep-sea sponges for our discovery study. A marine sponge Cladocroce sp. exhibited cytotoxic activity in the bioactivity screening. From this sponge a previously unreported cytotoxic glycosphingolipid, calyxoside B, was isolated and the structure of this compound was elucidated by analyses of MS and NMR spectra and chemical derivatization. We converted the ketone in the middle of a long aliphatic chain into an oxime to which was applied Beckmann rearrangement to afford two positional isomers of amides. The products were subjected to acidic hydrolysis followed by LC-MS analysis, permitting us to assign unequivocally the position of the ketone. Calyxoside B shows cytotoxicity against HeLa cells with an IC50 value of 31 µM and also weakly stimulated the production of cytokines in mice.

Highlights

From marine sponges a wide variety of bioactive secondary metabolites with unique structures have been discovered [1]
We examined the relative configuration of the vicinal amino alcohol in each head group after conversion to an oxazolidinone
Calyxoside B belongs to a group of two-headed glycosphingolipids which contain

Summary

Introduction

From marine sponges a wide variety of bioactive secondary metabolites with unique structures have been discovered [1]. Due to a great deal of effort devoted by natural product chemists to study their constituents, the frequency of rediscovery of known compounds has increased in recent years. Because of the lesser accessibility of deep-sea sponges, they are generally underexplored compared with those from shallow waters [2]. Investigation of such an untapped resource would lead to the discovery of new biologically active secondary metabolites. We have isolated calyxoside B (1) together with the known compound calyxoside (2) [5]. The position of the ketone in the middle of the long alkyl chain was determined after converting the ketone into two positional isomers of amides by the Beckmann rearrangement

Methods

Results

Conclusion