PROCESS FOR PREPARING ALLYLIC REARRANGEMENT COMPOUNDS OF ANTIBIOTICS SF-837 AND SF-837A2

1355578 Derivatives of antibiotics SF-837 and SF-837A, MEIJI SEIKA KAISHA Ltd 27 Oct 1971 [27 Oct 1970] 50014/71 Heading C2A Novel isomers of antibiotics SF-837 and SF-837A 2 are produced by subjecting the said antibiotics to treatment with aqueous acid at a pH from 1 to 5 for a sufficient time to cause allylic rearrangement thereof and recovering the rearrangement product from the reaction mixture. The isomers are believed to have the general formula wherein for the isomer of SF-837, R 2 is -COCH 2 CH 3 and for that of SF-837 A 2 , R 2 is -COCH 2 CH 2 CH 3 , R 1 being -COCH 2 CH 3 in each case. The preparative process is effected by dissolving the parent antibiotic in aqueous acid which may contain up to about 50% of watermiscible solvent (e.g. ethanol, acetone, dioxan or tetrahydrofuran), preferably at a pH from 2 to 3À5. The allylic rearrangement takes place over a period dependent upon the pH and temperature, suitable temperatures being between 10‹ and 80‹ C., preferably 15‹ to 50‹ C., a typical rearrangement process being conducted at pH 3À0 and 50‹ C. for 4 hours. The products consist of the desired isomer and unchanged parent antibiotic, e.g. in a ratio of 4 : 6 under favourable conditions, together with a variable amount of decomposition (hydrolysis) products. The acids used include hydrochloric, phosphoric, hydroiodic, hydrobromic, sulphuric, acetic, monochloro-, trichloro- and trifluoro-acetic, propionic, tartaric, oxalic, malonic, maleic, citric, p-toluenesulphonic and methane-sulphonic acids. The desired isomer may be recovered by bringing the reaction mixture to neutral or alkaline pH, extracting with a waterimmiscible solvent (e.g. ethyl acetate, chloroform or ether), evaporating the extract to dryness and washing the dry product with a little benzene to remove the parent antibiotics. The residue of isomer may then be recrystallized, e.g. from acetone. The novel isomers have activity against Grampositive bacteria and may be used in pharmaceutical compositions with a suitable carrier for topical, parenteral or oral administration.