Elsevier

Tetrahedron

Volume 74, Issue 52, 27 December 2018, Pages 7516-7521
Tetrahedron

Siladenoserinols M–P, sulfonated serinol derivatives from a tunicate

https://doi.org/10.1016/j.tet.2018.11.031Get rights and content

Abstract

Four new sulfonated serinol derivatives, siladenoserinols M–P (14), were isolated from a tunicate of the family Didemnidae collected in Indonesia. Their chemical structures were elucidated by the interpretation of NMR and mass spectroscopic data. Two of them (2 and 4) were revealed to be disulfonate serinol derivatives, and the others were monosulfonates. Siladenoserinols A (5) and B (6), which we previously isolated from the same tunicate, inhibited the p53–Hdm2 interaction with an IC50 value of 2.0 μM. However, 14 did not inhibit the activity. The result suggested that the acetyl group in the bicyclic ketal unit and/or the glycerophospholipid moiety in 5 and 6 were responsible for the inhibition of the p53–Hdm2 interaction.

Introduction

A number of biological active secondary metabolites have been discovered from tunicates and have been applied for drug development [[1], [2], [3]]. Tunicates contain species-specific chemicals, which are thought to be produced by the symbionts [4,5]. The family Didemnidae is known to be an especially rich source of biologically active compounds, including cyclic peptides [6], pyridoacridine-type alkaloids [7], and pyrrole-derived alkaloids [8]. Serinolipids have been isolated from several Didemnum species so far [[9], [10], [11], [12], [13]] and intriguing pharmacological properties such as cytotoxicity [9,10], antibacterial activity [11], and HIV-1 integrase inhibitory activity [12] were reported. In our previous study, twelve sulfonated serinol derivatives, siladenoserinols A–L, which were isolated from the tunicate of the family Didemnidae collected in Indonesia, were discovered to be inhibitors of p53–Hdm2 interaction [13]. In our continuing research on the constituents of the Didemnidae tunicate, four new sulfonated serinolipid derivatives, siladenoserinols M–P (14) (Fig. 1), were isolated. We here describe the isolation, structure elucidation, and biological activities of 14.

Section snippets

Isolation of sulfonated serinol derivatives

A tunicate of the family Didemnidae was collected in Indonesia in 2011 and the specimen was extracted with EtOH and then MeOH. The extract was partitioned between water and EtOAc, and the aqueous residue was successively extracted with n-BuOH. The n-BuOH fraction was concentrated and subjected to SiO2 and ODS column chromatography followed by HPLC purification to afford siladenoserinols M–P (14).

Structure elucidation of 1

Siladenoserinol M (1) has the molecular formula of C33H58N2O11S, as determined by HRESIMS. The 1H

General experimental procedures

Optical rotations were measured on a JASCO DIP-1000 polarimeter in MeOH. UV spectra were measured on a JASCO V-550 spectrophotometer in MeOH. The IR spectrum was recorded on a PerkinElmer Frontier FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on a JEOL JNM-ECX-400 or Bruker Avance III 600 NMR spectrometer in CD3OD. Chemical shifts were referenced to the residual solvent peaks (δH 3.30 and δC 49.0 for CD3OD). ESIMS spectra were measured on a Bruker amaZon speed mass spectrometer,

Acknowledgements

This work was partially supported by JSPS KAKENHI Grants 22406001 (S.T.), 17H03994 (S.T.), 18K06719 (H. K.), and 18K14933 (Y. H.).

References (17)

  • K.L. Rinehart

    Med. Res. Rev.

    (2000)
  • S.W. Taylor et al.

    Chem. Rev.

    (1997)
  • K.L. Rinehart et al.

    J. Nat. Prod.

    (1988)
  • E.W. Schmidt et al.

    J. Nat. Prod.

    (2012)
  • M. Tsukimoto et al.

    J. Nat. Prod.

    (2011)
  • A. Aneiros et al.

    J. Chromatogr. B

    (2004)
  • T.F. Molinski

    Chem. Rev.

    (1993)
  • F. Fan et al.

    Chem. Rev.

    (2008)
There are more references available in the full text version of this article.

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