(1) Field of the Invention
This invention relates to a novel process for conversion of the biologically inactive fermentation product, oxotomaymycin, to the antibiotic, tomaymycin, which has been demonstrated to have antitumor, antiviral and antibiotic activities.
(2) Description of the Prior Art
The antibiotic tomaymycin, having the formula ##STR1## is disclosed in J. Antibiotics 25: 437-444 (1972) as being isolated from the fermentation broth of Streptomyces achromogenes var. tomaymycetics. More recently, isolation of tomaymycin from a Nocardia species culture has been reported in Japanese Patent Publication No. 73195/79. Tomaymycin may be isolated either as a crystalline methanol adduct (formula I) or as desmethanol tomaymycin of the formula ##STR2## depending on the solvent used in the final step of its isolation. Both forms of the antibiotic appear to have antimicrobial, antiviral and antitumor activities.
While tomaymycin displays useful biological activities, another product of the same fermentation broth named oxotomaymycin has been disclosed in Chem. Pharm. Bull. 19: 2289-2293 (1971) as being biologically inactive. Oxotomaymycin has the structural formula ##STR3##
If available, a method to convert the biologically inactive fermentation product, oxotomaymycin, to tomaymycin (or desmethanol tomaymycin which can be easily obtained from tomaymycin by heating in a non-methanol solvent) would be of considerable utility. This is particularly true since tomaymycin and desmethanol tomaymycin are chemically unstable and their isolation from a fermentation broth is quite challenging, whereas, being much more stable, oxotomaymycin can be isolated in a straightforward manner. Thus, the preparation of tomaymycin could be greatly facilitated by first isolating oxotomaymycin and then converting this purified material to tomaymycin by a chemical procedure.
J. Am. Chem. Soc. 90: 5641-5643 discloses a total synthesis of anthramycin of the formula ##STR4## by a process involving the intermediate of the formula ##STR5## Attempts to reduce the tertiary amide group of this intermediate were unsuccessful, and it was necessary to prepare a benzoxazoline intermediate of the formula ##STR6## and then reduce this amide derivative to the desired carbinolamine product.