Cherbonolides M and N from a Formosan Soft Coral Sarcophyton cherbonnieri

Abstract

Two new isosarcophine derivatives, cherbonolides M (1) and N (2), were further isolated from a Formosan soft coral Sarcophyton cherbonnieri. The planar structure and relative configuration of both compounds were established by the detailed analysis of the IR, MS, and 1D and 2D NMR data. Further, the absolute configuration of both compounds was determined by the comparison of CD spectra with that of isosarcophine (3). Notably, cherbonolide N (2) possesses the unique cembranoidal scaffold of tetrahydrooxepane with the 12,17-ether linkage fusing with a γ-lactone. In addition, the assay for cytotoxicity of both new compounds revealed that they showed to be noncytotoxic toward the proliferation of A549, DLD-1, and HuCCT-1 cell lines. Moreover, the anti-inflammatory activities of both metabolites were carried out by measuring the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced generation of superoxide anion and elastase release in the primary human neutrophils. Cherbonolide N (2) was found to reduce the generation of superoxide anion (20.6 ± 6.8%) and the elastase release (30.1 ± 3.3%) in the fMLF/CB-induced human neutrophils at a concentration of 30 μM.

Keywords: Sarcophyton cherbonnieri; anti-inflammatory activity; cytotoxicity; isosarcophine derivatives; tetrahydrooxepane.

Figure 1

Marine natural products 1–3 isolated from the soft coral S. cherbonnieri.

Figure 2

COSY and selective HMBC correlations of 1 and 2.

Figure 3

Selective NOE correlations of 1.

Figure 4

CD spectrum (1.2 × 10^–4 M, MeOH) of 1 and CD spectrum (1.6 × 10^–4 M, MeOH) of 3.

Figure 5

Selective NOE correlations of 2.

Figure 6

CD spectra (1.2 × 10^–4 M, MeOH) of 2.

Scheme 1

Proposed biosynthetic pathway of cherbonolide N (2).