GB1303724A - - Google Patents

Abstract

1303724 Derivatives of the antibiotic wortmannin SANDOZ Ltd 27 April 1970 [14 May 1969 10 Sept 1969] 20182/70 Heading C2A The new fungistatic antibiotic 11-desacetoxywortmannin of Formula I may be prepared (a) by isomerizing #<SP>9(11)</SP>-8,9- dihydro - 1] - desacetoxy - wortmannin of Formula II or (b) by cultivating the S3196 strain of Penicillium funiculosum Thom preferably NRRL 3363, or the strain S8033/F of Aspergillus janus Raper and Thom, preferably NRRL 3807, or 11-desacetoxy-wortmannin producing mutants thereof in an aqueous nutrient medium containing assimilable carbon and nitrogen sources and inorganic salts, and isolating the resulting 11- desacetoxy-wortmannin. Preferably the isomerization is effected in an anhydrous organic base such as pyridine or quinolone under reflux in a nitrogen atmosphere and the product is recrystallized. In process (b) the antibiotic is isolated from the culture filtrate by extraction with ethyl acetate, benzene, chloroform, butyl acetate, methylene chloride or butanol, removal of solvent and optional chromatographic purification of the residue on e.g. alumina, silica gel or magnesium silicate, or by countercurrent distribution. #<SP>9(11)</SP> - 8,9 - Dihydro - 11 - desacetoxy - wortmannin is prepared by reacting wortmannin of Formula III under anhydrous conditions with zinc dust in an organic solvent in the presence of an acid. Pharmaceutical compositions having fungistatic, oedema- and inflammation-inhibiting effects comprise 11-desacetoxy-wortmannin and a pharmaceutical carrier or diluent. The compositions may be administered orally or topically in the form of powders, sprays, ointments, or tinctures.