The Isolation of Secondary Metabolites from New Zealand Marine Sponges

Abstract

A study of an undescribed New Zealand marine sponge of the genus Mycale sp. using cyclic loading and reverse phase poly(styrene-divinylbenzene) chromatographic support has resulted in the isolation of two new biologically active compounds, peloruside A (59), and mycalamide D (62), Peloruside A (59), is a l6-membered polyoxygenated macrolide, that was found to have potent cytotoxic activity in the nanomolar range. The structure and relative stereochemistry of the ten stereogenic centres were determined on a 3.0 mg sample using a variety of spectroscopic methods. Mycalamide D (62), is a l3-des-O-methyl analogue of mycalamide A (56). It was found to have cytotoxic activity approximately 20-fold less than that of 56. An analytical method was developed for the quantification of mycalamide A (56), pateamine (58), and peloruside A (59) in Mycale sponge tissue samples. The method using 1H NMR allowed the simultaneous quantification of all three compounds and was found to have an error below 10%. A study was undertaken to determine the effect of location, season and depth on the concentration of these metabolites in Mycale sp.. The concentrations of these compounds showed different geographic, seasonal, and environmental relationships. A generic method using cyclic loading, PSDVB, and 1H NMR spectroscopy to screen sponges for compounds with potential biologically activity was developed. Several known compounds and eight new compounds were isolated. These included four new clerodane diterpenoids (86-89), and three new l9-nor-clerodanes (90-92) from the sponge Raspailia topsenti. Diterpenoids 86-89 were found to have an uncommon cis-ring fusion and all the metabolites were found to have a rare configuration at C-8. Compounds 90-92 represent the first nor-clerodane diterpenoids isolated from the marine environment. Raspailol (87) was found to exhibit anti-inflammatory activity. A novel sulfamic acid containing indolo[3,2-a]carbazole, vulcanellamine (93), was also isolated from an undescibed species of the sponge genus Vulcanella. The structure was determined by spectroscopic methods and chemical interconversions. This compound represents the first indolo[3,2-a]carbazole from a natural source and contains the unusual sulfamic acid functionality.