3-amino-4-(2-hydroxyethylthio)-2-oxo-azetidine derivs-pref contng ant - n-acyl derivs -intermediates for cpds with antibacterial activity

摘要

Cpds. of gen form (I) where Ra1 = H or an amino-protecting group RA1; Rb1 = H or an acyl group Ac1; or Ra1 + Ra1 Rb1 for a bivalent amino-protecting group; R2 = H or acyl Ac2; each or R3 and R4 = H or an organic residue bound via a C-atom; or salts of (I) with salt-forming groups, are prepd. by reacting a bis(cis-3-N-RA1- N-Rb1-amino-2-oxo-4-azetidinyl)-disulphide of formula (II) with an oxiran cpd (III) and simultaneous reaction with a reducing agent. In cpd. (I) where R2 = H the OH gp. may be exchanged for acyloxy and/or when RA1 and/or Rb1a = Ac or RA1 + Rb1 = a bivalent amino-protecting group these may be split off and/or the free amino group may be protected and/or a salt may be exchanged for a free cpd. or another salt and/or a free cpd. may be exchanged for a salt and/or an isomeric mixture may be separated into isomers. The preferred reducing agents used are Zn, its alloys or amalgams or Mg, pref. in the presence of acids, acid agents or alcohols pref. with addition of water. Other reducing agents are alkalimetal- or Al amalgams in the presence of moist solvents or Cr II cpds. pref. in aqueous medium. The pref. acyl group Ac1 is an N-acyl deriv of a 6-APA or 7-amino-ceph-alosporanic acid cpd-contg. acyl gp. of an organic carboxylic acid or of a carbonic acid semi-deriv. (I) are intermediates in the synthesis of other cpds. esp. those of the type 7beta-amino-ceph-3-em-4-carboxylic acid and its N-acyl derivs which have ant-microbial activity such as against Gram-+ve and Gram-ve bacteria. In an example ethyleneoxide and Zn-dust are added to bis-(cis-2-oxo-3beta-phenylacetylemino-4beta-azetidinyl)-disulphi- de in aq. acetic acid to give 4beta-(2-hydroxyethylthio)-3beta-phenylacetylamino-azetidin-2-one.