The Isolation and Structure Elucidation of Novel, Anti-Inflammatory Secondary Metabolites from New Zealand Marine Invertebrates

Abstract

The aim of this study was to isolate novel anti-inflammatory secondary metabolites with potential to be developed as nutraceuticals or pharmaceuticals from marine invertebrates. Two classes of marine invertebrates, Porifera and Echinodermata were chosen for the study. A continued investigation of the New Zealand sponge Raspailia topsenti (Porifera) resulted in the isolation of several known and three novel diterpenes. Raspailenone B (27) is a clerodane diterpenoid with the uncommon cis-ring fusion. Topsentane A (28) and topsentane B (29) are 19-nor-clerodanes with an additional furan ring and are the first compounds of this type to be isolated from the marine environment. Topsentanes A and B exhibit anti-inflammatory activity. Sea cucumbers (Echinodermata) were selected for this study since they have been used for over 5000 years in traditional medicine and as health products. Investigation of the New Zealand sea cucumber Australostichopus mollis resulted in the isolation of one known triterpene glycoside, neothyonidioside (79) and four novel monosulphated triterpene glycosides mollisoside C (78), mollisoside D (80), mollisoside A (81), and mollisoside E (82). A combination of normal and reverse phase chromatographic separations, guided by mass spectroscopy, was used to separate the closely related glycosides. A variety of spectroscopic methods was used in elucidating the structures and determining the relative stereochemistry of the novel compounds. Glycoside mixtures and two of the pure compounds (78) and (79) were tested for anti-inflammatory activity and found to be more active than aspirin. Glycoside mixtures also exhibited anti-fungal activity and were found to be non cytotoxic.