A New Sesterterpene, Sch 599473, from a Marine Sponge, Ircinia sp.

Abstract

mediates an essential event for antigen-specific T cell activation and an important mechanism for mounting an immune response.6) Thus, CCR7 could be a potential target for treatment of various metastases and/or inflammatory conditions.In this study, a fraction from a sponge was identified which showed inhibitory activity in the CCR7 receptor In the primary HTS assay, a sample in the MFL from a active fraction was subjected to further purification. The preliminary CG161 fractions were prepared as previously described.4,8) In this study, fraction 3 (50% acetonitrile (ACN) elution) was active in the CCR7 binding assay. Fraction 3 (35mg) was further purified on an HPLC ACN gradient system (15ml/minute, 2% to 30% ACN over 40 minutes, and 30% to 70% ACN over next 40 minutes), to yield -100 fractions (13ml/fraction). Two pure compounds 2 (1.8mg) and 1 (0.9mg) were obtained with retention time -54 minutes and -57 minutes, respectively. Detailed NMR analysis9) idetified 2 as sulfircin, a compound whose structure had been determined previously by X-ray crystallography.10)The structure of 1 was determined based on extensive NMR and HRMS analyses and by comparison to 2.11) From the high-resolution negative ion ESI-MS, the molecular formula of 1 was established as C25H39O5S (found m/z 451.2529; calcd. 451.2523 for [M]-). All spectral data including the HRMS, 1H and 13C NMR data strongly suggested that 1 was structurally related to 2. The 13C

Marine natural products

“…342 Darwinella australensis collected from NW Australia contained sesterterpenoid sulfates 378-380 that inhibited the cell division of sea urchin eggs, but were not cytotoxic to human leukemia cells. 343 An Ircinia species collected at -70 m by dredging in the Gulf of Mexico contained a tricyclic sesterterpenoid, Sch 599473 381, 344 while the Antarctic sponge, Suberites caminatus yielded the rearranged sesterterpenoid aldehyde caminatal 382. 345 An asymmetric synthesis of (−)-cacospongionolide F, isolated from Fasciospongia cavernosa, 346 confirmed the original stereochemical assignments.…”

Marine pharmacology in 2003–4: Marine compounds with anthelmintic antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action

“…With the purpose of contributing to the discovery of small molecule agonists and antagonists of chemokine receptors, Yang et al (Yang et al, 2003d), reported a new sesterterpene sulfircin (89) purified from the marine sponge Ircinia sp. that inhibited the CCR7 chemokine receptor, a receptor involved in the regulation of T cells and dendritic cell mobilization into lymphoid organs.…”

Sesterterpenoids

“…90 An Ircinia species collected at −70 m by dredging in the Gulf of Mexico contained a sesterterpenoid 169. 91 Stoeba extensa (Japan) gave the cytotoxic halisulfate 7 165; 92 the C-8 stereochemistry of halisulfate 7, originally isolated from a Coscinoderma species, 89 has been revised to that shown as 170 on the basis of careful NOE analysis. 92 Two new sesterterpene sulfates, hipposulfates A 171 and B 172, have been isolated from an Okinawan sponge, Hippospongia cf.…”