Renieramycins M (1m) and N (1n) were isolated from the Thai sponge Xestospongia sp., pretreated with potassium cyanide in methanolic buffer solution, and their structures and relative stereochemistries were elucidated on the basis of spectroscopic data. This strategy is the first example of the gram-scale preparation of this series of compounds and presents a potential solution for increasing the gram-scale supply of novel natural products from marine sources.

Four minor renieramycin-type derivatives, including renieramycins O (1o) and Q-S (1q-s), were isolated from the sponge Xestospongia sp. pretreated with potassium cyanide. Their structures were elucidated by comparison of spectral data with those of recently reported renieramycins M (1m) and N (1n). The results of transformation and cytotoxicity measurements are also described.

No abstract

The nudibranch Jorunna funebris (Mollusca: Gastropoda: Opisthobranchia: Nudibranchia: Kentrodorididae) is one of the marine, slug-like invertebrates belonging to phylum Mollusca that lacks a protective hard shell.1) This nudibranch and other dorid nudibranchs can accumulate secondary metabolites that are derived from dietary organisms in order to protect themselves from predators.2-4) J. funebris is carnivorous and feeds mainly on sponges such as Xestospongia sp., Haliclona sp., Euplacella cf. australis, 5) and Oceanapia sp. 6) In 1988, de Silva and Gulavita isolated several simple isoquinolinequinones including renierol acetate (4a), renierol propionate (4b), N-formyl-1,2-dihydrorenierol acetate (5a), and Nformyl-1,2-dihydrorenierol propionate (5b) from Xestospongia sp. and its associated nudibranch J. funebris, but no bistetrahydroisoquinolines.7-9) An in-depth chemical analysis of the mantle and mucus of the Pacific nudibranch J. funebris by Fontana et al. resulted in the isolation of the bistetrahydroisoquinoline jorumycin (6), the primary assay of which revealed cytotoxicity against NIH 3T3 fibroblast cells and against some tumor cell lines, such as P388 mouse lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma, and MEL28 human melanoma, at very low concentrations. 10) Compound 6 shows the promising antitumor properties: however, it is available only in very minute quantities, because 6 has relatively an unstable carbinolamine functional group that may be decomposed during isolation procedure. To obtain sufficient quantities of more stable derivatives with retention of bioactivity, we reported that ecteinascidin 770 was isolated from the Thai tunicate Ecteinascidia thurstoni pretreated with KCN in methanolic buffer solution.11) Furthermore, we have recently succeeded the isolation and structure elucidation of renieramycin M (2m) with gram-scale supply from a Thai sponge Xestospongia sp. that was also pretreated with KCN.12) As series of our search for new metabolites via the isolation and characterization of biologically active compounds from Thai marine animals, we found the Thai nudibranch J. funebris feeding on the blue sponge Xestospongia sp., growing around Sichang Island in the Gulf of Thailand. In this paper, we present the isolation, structure elucidation, and cytotoxicity of three stabilized bistetrahydroisoquinolines jorunnamycins A-C (1a-c) from the KCN-pretreated J. funebris. The preparation of a carbinolamine analog 1d from 1c and its chemical stability are also reported. Results and DiscussionJ. funebris (20 animals; 500 g, wet weight) was collected in the vicinity of Sichang Island at the depth of 3-5 m in March 2004 and its egg ribbons (23.2 g, wet weight) were separately obtained in November 2004. The animals were carefully dissected into two parts, the mantles and the visceral organs (the combined digestive glands and gonads). Then, the three parts were separately homogenized with phosphate buffer (pH 7). Aqueous KCN solution was added to each suspension, the mixture was macera...

No abstract

Under novel conditions of culture, Streptomyces lavendulae No. 314 was found to produce new antibiotics, chlorocarcins and mimosamycin in addition to streptothricin. The antibiotics are extracted from culture filtrate with organic solvents and further purified by silica gel chromatography. Chlorocarcins A, B, and C are closely related basic antibiotics which are active against gram-positive bacteria , EHRLICH carcinoma and L 1210 leukemia of mice. Mimosamycin is a neutral antibiotic which is mainly active against mycobacteria. Production, isolation and physicochemical properties of the antibiotics are described.As the new sources of streptomycetes and streptoverticillia starting to dwindle , the chances to find new antibiotics seem to have become increasingly poor, and a current screening techniques among streptomycetes often lead to known substances. On the other hand, the application of more sensitive and selective detection techniques has continued to provide new and interesting antibiotic substances. A sensitive and rational antitumor cell screening system was developed recently in our laboratory employing suspension culture of L 1210 murine leukemia cell line.') During the course of the antitumor cell screening using this system, the culture filtrate of a strain of streptomyces, designated as No. 314, was found to be cytocidal and antibacterial with activity against Bacillus subtilis and Escherichia coli. The major antibiotic produced by the strain in a submerged state under regular culture conditions proved to be a streptothricin complex') which apparently is devoid of antitumor activity. During the study of the detailed culture conditions for the production of satellite antibiotics of streptothricin, our group have isolated mimosamycin, an antibiotic which is mainly active on mycobacteria including streptomycin-resistant strains of human tubercle bacilli and three antitumor antibiotics, chlorocarcins A, B, and C. This paper describes the production of these antibiotics and their physicochemical characterization. Antibiotic ProductionThe organism used in this investigation was Streptomyces sp. No. 314 which was later identified as a strain of Streptomyces lavendulae.3) The culture was maintained in the lyophilized state. A freshly grown slant on glucose-asparagine agar (KRAINSKY) was used for the inoculum of laboratory-scale antibiotic production. Laboratory fermentation was run in 500-ml shake

A structure is assigned to saframycin A, a novel antitumor antibiotic from Streptomyces lavendulae No. 314, on the basis of 13C NMR-spectral data.

No abstract