We have isolated the small, highly strained carboxylic acid cycloprop-2-ene carboxylic acid from the Asian toxic mushroom Russula subnigricans. This compound is responsible for fatal rhabdomyolysis, a new type of mushroom poisoning that is indicated by an increase in serum creatine phosphokinase activity in mice. We found that polymerization of the compound at high concentrations via ene reaction abolishes its toxicity.

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In a previous study, we reported a novel 14-membered ring macrolide, migrastatin isolated from culture broth of Streptomyces sp. MK929-43F1 as an inhibitor of tumor cell migration1). Recently, however, we found that our original migrastatin isolate contained teleocidin-related compounds which display strong inhibitory activity against tumor cell migration. In this report, we describe the effects of teleocidin-free migrastatin on tumor cell migration and on the growth of several types of tumor cells. Whenthe original migrastatin sample was subjected to HPLC (Capcell Pak C18 column, 20X250mm) developing with 70% aq acetonitrile, a potent migration inhibitory activity was eluted in a fraction other than migrastatin, indicating that the migration inhibitory activity of our original migrastatin samples reported previously was due to the activity of an impurity. The potent migration inhibitory fraction contained teleocidin-related compounds, as judged from UV spectrum. Teleocidin-related compounds are knownto inhibit [3H]PDBu binding to the cell surface2), therefore, we clarified the content of teleocidin-related compoundsin the original migrastatin sample as evaluated by [3H]PDBu binding assay (Fig. 1) migrastatin reported previously4), possibly due to the low content of impurities. Migration inhibitory activities of pure migrastatin and pendolmycin were assayed by the wound healing method as described before1^In brief, a standardized scratch was madethrough a con fluent monolayer of humanesophageal carcinoma EC17cells, and then the cells from the cut edge were allowed to migrate for 24 hours5). Pendolmycin as well as teleocidin B inhibited migration of EC17 cells at lOng/ml (data not shown). On the other hand, EC17 cells migrated inwardly and covered a great area of the scratch even in the presence of 100 /ig/ml of migrastatin. However, when the EC17 cells were pretreated with migrastatin

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from Streptomyces sp. MK929-43F1 Sir: Wehave isolated migrastatin (Fig. 1), as an inhibitor of tumor cell migration, from a cultured broth of Streptomyces sp. MK929-43F1. In the preceding paper1}, the taxonomy, fermentation, isolation and biological activities were reported. In this paper, we describe the physico-chemical properties and structure elucidation of migrastatin. Physico-chemical properties of migrastatin are summarized in Table 1. Migrastatin is readily soluble in methanol, acetone, ethyl acetate, chloroform and DMSO and practically insoluble in water and?z-hexane. Migrastatin was isolated as a white powderwith melting point of 54~55°C. The UV spectrum showed end absorption. Migrastatin gave positive color reaction with molybdophosphoric acid-sulfuric acid and 2,4-dinitrophenylhydrazine but negative with ninhydrin and Rydon-Smith. The molecular formula for migrastatin was established as C27H39NO7 by HRFAB-MS, which was supported by the *H and 13C NMRspectra. The DEPT and HMQCspectra exhibited 27 resonances; three methyl, one methoxy, seven methylene, five methine, one oxygen bearing methine, five olefinic methine, one quaternary olefinic and four carbonyl