XYLOSTASIN DERIVATIVES AND THE PRODUCTION THEREOF

摘要

1481019 Xylostasin phosphates TAKEDA YAKUHIN KOGYO KK 2 July 1974 [9 July 1973] 29263/74 Heading C2P The invention comprises the 31-, 511-, and 31,511-diphosphate of xylostasin which has the formula and a salt, especially a physiologically tolerable salt thereof. The phosphates may be obtained by contacting xylostasin in a solvent or diluent and in the presence of a phosphate donor with cells of or cell material derived from a microorganism which belongs to the genus Escherichia or Achromobacter and which is resistant to at least 100 Ág. xylostasin per ml. Specified microorganisms are Escherichia coli (ATCC 21990) and Achromobacter xylosoxydans (ATCC 31040) whose microbiological characteristics are described. The cells may be obtained by propagating the microorganism in a medium containing one or more carbon sources, one or more nitrogen sources and one or more inorganic salts and the cultivation may be performed by the stationary cultural method or by the aerobic stirring method and the disrupted cells or cell material may be obtained by subjecting the culture broth or the cell material isolated therefrom to a suitable physical or chemical treatment. In the phosphorylation the solvent or diluent may be water or the cellcontaining culture broth may be employed and the phosphorylation is preferably effected at 30‹ to 40‹ C. and at pH 6 to 10. The xylostasin phosphate ester products may be converted to a corresponding product wherein the phosphoric ester group is replaced by a halogen atom, i.e. to the corresponding halogenodeoxy- (or dihalogenodideoxy-) xylostasin and, if desired, the latter can then be reduced to form the corresponding deoxy- or dideoxyxylostasin which are useful antibiotics. The conversion of the phosphate to the halogenodeoxyxylostasin may be effected by protecting the free amino and hydroxy groups of the phosphate or diphosphate, e.g. by reaction with a silylating agent, e.g. hexamethyl disilazane, or an acylating agent, e.g. acetic anhydride, reacting the protected compound with a halogenation agent, e.g. trimethylsilyl chloride, and removing the protecting groups. Detailed examples are given for the production of xylostasin 31-phosphate and xylostasin 511-phosphate respectively and for the conversion of the 31- phosphate to 31-chloro-31-deoxy-xylostasin and the reduction of the latter by means of a current of hydrogen gas in the presence of Raney nickel and triethylamine to form 31- deoxy-xylostasin. Specification 1,460,039 is referred to.