Sch 56396: A New c-fos Proto-oncogene Inhibitor Produced by the Fungus Tolypocladium sp.

Our previous investigation of searching for novel c-fos proto-oncogene inhibitors led to the discovery of two new diketopiperazines related to verticillin family of compounds from the fungus, Gliocladium sp.1) As a result of continued efforts of our natural product program in the anticancer therapy area, a newcompound, Sch 56396 (1), was isolated from the fermentation broth of a fungal culture (SCF-0729), Tolypocladium sp. This study describes the fermentation, isolation, structure elucidation and biological activity of 1. The microorganism, Tolypocladium sp., was isolated from dead twigs from a Quercus virginiana Miller, an old live oak tree in the state of Tamalupas, Mexico1". The fungus was grownin a two stage germination prior to inoculation into a large-scale fermentation. The first stage germination consisted of inoculating 2.5 ml of a frozen whole broth sample of the producing strain in a 250ml Erlenmeyer flask containing 50 ml ofa mediumconsisting of (g/liter): Difco yeast extract 3 g, proteus peptone 5 g, NaCl 5g, KH2PO4 5g, cerelose 2g, soybean grits 5g,