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Very recently, ToMITA and coworkers' 2) have reported the fermentation, isolation and structure elucidation of gilvocarcins V (1) and M (2). They note that I was previously described under the name of toromycin by HORII et al.3) although the structure of toromycin was not elucidated. Recently we have isolated 1 and 2 and a related compound gilvocarcin E (3) from a culture of Streptomyces anandii subsp. araffinosns strain C-22437 (ATCC-31431).* The producing culture was isolated at BristolLaboratories from a soil collected in Katpadi, Madras, India. We report here the isolation, structure elucidation and biological activities of compounds 1. 3. Isolation of Gilvocarcins V, M and E

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Six anthracycline antitumor agents, marcellomycin, musettamycin, rudolphomycin, alcindoromycin, collinemycin, and mimimycin, have now been isolated from bohemic acid complex. This has been achieved by classical column chromatography with Sephadex LH-20 and ammonia-neutralized silica and by analytical and prepatative hplc techniques with normal phase systems containing aqueous ammonia.

In a screening program for antitumor substances from microbial fermentations, a compound was isolated from the mycelium of an Aspergillus species which proved to be the mycotoxin 5-methoxysterigmatocystin. This and the subsequently isolated sterigmatocystin gave significant inhibition of the transplanted mouse leukemias P-388 and L-1210. Preparation and testing of several derivatives of 5-methoxysterigmatocystin suggest that certain functions in the molecule are essential for tumor inhibition. Although slight antitumor effects have been reported for the chemically related aflatoxins, we believe this is the first report of antitumor activity of sterigmatocystins.During the course of screening fungal fermentations for antitumor effects, weak inhibition of P-388 lymphatic leukemia was noted with filtrates from an Aspergillus species. The original broth had only slight antimicrobial activity and was without effect at 1:10 dilution on either HeLa or KB cells in tissue culture. Refermentations conducted in an effort to optimize conditions gave highly variable antitumor effects. The reason for this became apparent as a result of a preliminary extraction which indicated virtually all the active principle was in the mycelium. A crudely crystalline solid with significant antitumor activity was recovered in the first such extraction. Subsequent isolation and purification established that the active substance was the well-known mycotoxin 5-methoxysterigmatocystin (5-MS), for which antitumor effects have not previously been described. The fermentation. isolation, chemical preparation, and antitumor effects of several sterigmatocystins are presented. Vegetative culture (4 ml) was transferred to a 500-ml Erlenmeyer flask with 100 ml of production medium consisting of 2% glucose, 3% Staclipse J starch, 2% washed brewers' yeast, and 0.5% CaCO,. MATERIALS AND METHODS ProductionThe production culture was incubated at 27 C on a shaking machine rotating at 270 rpm. Samples were taken after 5, 6, and 7 days of incubation, and the mycelium was extracted with acetone. The quantity of 5-MS in the extract was estimated chromatographically using a silica gel thin-layer plate and a solvent system consisting of 1% methanol in toluene. The agent was made visible with ultraviolet light. Tank fermentations were carried out with the same vegetative culture medium and production medium as used in flasks. A seed tank with 6 gallons (ca. 23 liters) of vegetative culture medium was inoculated with 100 ml of spore suspension. The culture was incubated for 48 h at 81 F (27.2 C) with 0.7-ft2/min r flow and 3-lb/in2 back pressure without agitators. The 10-gallon (ca. 38 liters) production broth was inoculated with 0.5 gallons (ca.