VERFAHREN ZUR HERSTELLUNG VON NEUEN PENICILLINEN

摘要

1426869 Organic compounds ASTRA LAKEMEDEL AB 12 March 1973 [13 March 1972] 11687/72 Heading C2C [Also in Division A5] Novel penicillins of Formula I and therapeutically acceptable salts thereof wherein R1 is phenyl, naphthyl, phenoxy or a heterocyclic group, such groups being optionally substituted with one or more amino, methoxy, hydroxy halogen or phenyl groups; R3 is H or CH 3 ; R4 is C 1 -C 8 alkyl, C 3 -C 7 cycloalkyl, phenyl or benzyl, such groups being optionally substituted with one or more azido, amino, substituted amino, nitro or C 1 -C 4 alkoxy groups; X is H, azido or hydroxy; and n is 0 or 1; provided that X is not H or azido when n is 1, R4 is an unsubstituted C 1 -C 8 alkyl group and R1 is thienyl, furyl, phenyl or hydroxy and/or halogen-substituted phenyl, are prepared (a) by reacting a compound of formula wherein R1' is R1 as defined above or a protected R1 group, X1 is X as defined above or a protected X group; n is 0 or 1 and -COZ is an acid chloride or equivalent group, with a compound of formula wherein R3 and R4 are as defined above and, if necessary, removing the protecting groups; or (b) by reacting a natural penicillin of Formula X wherein R.CO is the acyl group of the natural penicillin and M is H or an alkali metal cation, with a compound of formula wherein R3 and R4 are as defined above and Y1 is halogen or an equivalent group to form an ester of formula wherein RCO, R3 and R4 are as defined above, which ester is reacted with a phosphorus halide, reacting the resulting imino halide with an alcohol and reacting the resulting imino ether with a compound of formula wherein R1', X1, n and -COZ are as defined above, and, if necessary, removing the protecting groups; or (c) by reacting a compound of formula wherein n is 0 or 1, and R1' and X1 are as defined above with a compound of formula wherein Y1 is halogen or an equivalent group and R3 and R4 are as defined above. The compound X may be in the form of its tetrabutylammonium salt. Pharmaceutical compositions comprise a compound of Formula I or a therapeutically acceptable salt thereof with a pharmaceutically acceptable diluent. Other antibiotics may be present in the compositions (see Division A5).