Novel sponge-derived amino acids. 12. Tryptophan-derived pigments and accompanying sesterterpenes from Fascaplysinopsis reticulata

Abstract

3403L) during 5-6 h of stirring. The extract was evaporated under vacuum, yielding an oily residue (9 g), which was redissolved in methylene chloride-methanol (191,20 mL) and fractionated on a column (200 mL) of E.M. silica gel 60 (230-400 mesh) packed in hexanemethylene chloride (1:l). Elution of the column was carried out by a step gradient of methylene chloride in hexane yielding partially purified compound in the 80% methylene chloride fractions. After evaporation of the solvent under reduced pressure, the residue (600 mg) was taken up in methanol (4 mL). Upon refrigeration, a precipitate formed which was removed by filtration. The filtrate was further fractionated in two identical runs (2 mL each) on a Rainin Dynamax 60A C1a column (1 in. X 25 cm), eluted with a 15 mL/min gradient of acetonitrile-water (713 to 91) over 40 min. Appropriate fractions were evaporated to dryness, yielding variecolin (95 mg); the homogeneity was verified by HPLC (Whatman Partisil ODs-3) eluted with acetonitrileH20 (3:1, k'5.2) and by TLC on silica gel 60 Fm (E. Merck) (R, 0.40 in CHzClz and R, 0.52 in hexane-acetone, 41) and Whatman KC18 plates (R, 0.43 in ACN-H20, %lo, and R, 0.50 in MeOH-H20, 955).Variecolin (1): [aID -11.5O (c 0.50, ACN); EI-MS mlz 360This paper reports the bioactive constituents of Fascaplysinopsis reticulata collected from the Benga Lagoon of the Fiji islands. The previous literature of this genus includes two aplysinopsins (monomeric tryptophans) from F. reticulata, as well as fascaplysin (Sa) (an apparent tryptophan dimer) and luffariellolide (3) (a seaterterpene) from Fascaplysinopsis sp. Our investigation of F. reticulata has revealed new seaterterpenes isodehydroulTarieUolide (1) and dehydroluffariellolide diacid (2); unique alkaloid-sesterterpene salts fascaplysin A (5b) [fascaplysin cation/dehydroluffariellolide diacid anion] and homofascaplysin A cation/dehydroluffariellolide diacid anion (6); and novel neutral alkaloids homofascaplysin C (7), homofascaplysin B (8), and secofascaplysin A (9). These substances were accompanied by fascaplysin (Sa) and the known alkaloid (+)-&pamine 4. The most important findings in this study are (a) fascaplysin derivative 5b is the first known salt comprised of a complex alkaloid cation and a terpene carboxylate anion, and (b) secofascaplysin A (9) is the first naturally occurring @xrbolinone. An amino acid biogenesis pathway is outlined for each of the above alkaloids. The biological activity profile against the HIV reverse transcriptase is reported for selected metabolites.Nitrogen-containing metabolites are rarely observed from Dictyoceratid sponges as this group is an excellent source of di-or sesterterpenes.'J A few atypical members of the Dictyoceratid family Thorectidae are sources of both sesterterpenes and amino acid derivative^.^^^ In 1985 we collected Fascaplysinopsis reticulata (Thorectidae family, Dictyoceratida order) which were eye-catching because of their massive, globular, and shiny red-brown appearance? This sponge was targeted for further study wh...

3-Bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian

“…The 1 H NMR data were similar to those reported for homofascaplysin A ( 2 ), 7 the major difference being the loss of an aromatic proton signal in 1 compared to 2 . Comparison of the molecular formulae of 1 and 2 showed that 1 was the bromo-analogue of 2 .…”

“…5 We revisited the ascidian, Didemnum sp., that we previously studied 6 and discovered a new related compound, 3-bromohomofascaplysin A ( 1 ), along with homofascaplysin A ( 2 ) 7,8 and fascaplysin ( 3 ). 1 The genus Didemnum is known to contain structurally diverse biologically active compounds such as cyclic peptides with characteristic modified amino acids, 9 pyridoacridines, 10 β-carbolines, 11 lamellarin, 12 3,4-substituted maleimides, 13 and polysulfide alkaloids.…”

Novel Antitumor Agents: Marine Sponge Alkaloids, their Synthetic Analogs and Derivatives

“…Biogenetically, ma'edamines A and B may be generated from 11, 12-dehydro form of aplysamine-2 or purpuramine H through formation of a 6-membered ring and dehydroxylation. 6 antimalarial, potency to numerous cancer cell lines [26][27][28][29][30][31]. Compounds 24, 25, 26-29 were screened in vitro for solid tumor selectivity against a panel of human and murine tumor cells [32,33].…”

Investigations on the Reactivity of Fascaplysin, Part II, General Stability Considerations and Products Formed with Nucleophiles

“…± The red pigment fascaplysin (1) was isolated in 1988 from the Fijian sponge Fascaplysinopsis Bergquist sp. [1], and more recently from its relative Fascaplysinopsis reticulata as a complex with dehydroluffariellolide diacid monoanion [2]. Antibiotic and antiproliferative properties of this natural product have been reported [1] [3].…”

“…A precedent for this compound class has been described earlier with the natural product reticulatine 2b, the methyl ester of 2a. Reticulatine was isolated as a salt with accompanying sesterpene dehydroluffariellolide diacide anion from Fascaplysinopsis reticulata [2]. Since the ring system of fascaplysin was found to be unstable in the presence of OH À , non-nucleophilic bases such as Et 3 N, N,N-diisopropylethylamine ( i PrEt 2 N), or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were used to reversibly produce the deprotonated form 1B.…”