Theopalauamide

Theonellamides A-E (1104-1108), which are analogs of the previously isolated theonellamide F (7), were characterized from the Japanese sponge Theonella sp. (7725). The related theopalauamide (= P951) (1109) was isolated from Theonella swinhoei found in both Palau and Mozambique (1126,1127). It should be noted that a minor structural correction (misplaced methyl group) has been reported for the previously known theonegramide (1128). 

Schmidt EW, Bewley CA, Faulkner DJ (1998) Theopalauamide, a Bicyclic Glycopeptide from Filamentous Bacterial Symbionts of the Lithistid Sponge Theonella swinhoei from Palau and Mozambique. J Org Chem 63 1254... 

Over half of the compounds reported for lithistid sponges were isolated from Theonella (family Theonellidae). Theonella species have been reported to contain a wide variety of cyclic and linear peptides and polyketides, as well as 3-alkyl piperidine derivatives nearly identical to those reported from the order Haplosclerida.58 There is also a single report of cyano- and isothiocyano-sesquiter-penes similar to those isolated from Axinellidae (order Halichondrida).42 Bewley et al. performed a cellular localization study on Theonella swinhoei in which several types of microorganisms were separated from the sponge cells. Chemical analysis of the extracts from the separated cells indicated that the bicyclic peptide theopalauamide was found exclusively in filamentous bacteria while the polyketide swinholide A was localized to a mixed population of unicellular bacteria.59... 

Schmidt, E.W., Bewley C.A., and Faulkner, D.J., Theopalauamide, a bicyclic glycopeptide from filamentous bacterial symbionts of the lithistid sponge Theonella Swinhoei from Palau and Mozambique, J. Org. Chem., 63, 1254, 1998. 

Metagenomic approaches have been used to study metabolites produced by bacterial symbionts of marine animals, insects, and nematodes. The literature now provides several examples where DNA-based strategies targeting specific genetic loci have enabled the isolation and cloning of biosynthetic gene clusters encoding for the biosynthesis of important symbiont-associated molecules such as pederin, onn amide A, bryostatins, trunkamide, theopalauamide, and the patellamides. These studies are the focus of another chapter in this series and therefore will not be discussed here. 

The SIO-RU-SKB collaboration also involved the collection, in 1994 and 1995, of over 100 marine invertebrates from the Ponto do Ouro area of southern Mozambique, about 80kms north of Sodwana Bay Fig. (1). Two cyclic peptides, the known swinholide A (78) and the new bicyclic theopalauamide (79), were isolated from Mozambique specimens of the Indo-Pacific lithistid sponge Theonella swinhoei (Family Theonellidae) [79]. Interestingly, a concurrent investigation of T. swinhoei from Palau,... 

Micronesia revealed that the source of 78 and 79 was not the sponge but rather the symbiont unicellular bacteria and filamentous eubacteria resident in the interior of T. swinhoei [80]. Swinholide A was reported to be toxic to L1210 (IC50 = 21 nM) and KB (IC50 = 28 nM) cell lines [81]. Theopalauamide inhibited the growth of Candida albicans in the standard paper disk assay at a concentration of 10 pg/disk. 

During their studies on symbiotic filamentous eubacteria found in the interior tissue of Theonella swhinoei from Palau, Faulkner et al. isolated a bicyclic glycopeptide, theopalauamide (42) [33]. Its molecular formula, deduced by HR mass measurements, differs from that of theonegramide... 

Theopalauamide Theonella swinhoei Palau, Mozambique Schmidt eto/., 1998... 

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