| 摘要 |
<p>1289796 Producing ampicillin TOYO JOZO KK 19 April 1971 [27 Feb 1970 24 Sept 1970] 23549/71 Heading C2A Ampicillin is produced by esterifying penicillin G to protect the 4-carboxyl group, reacting the ester with a chlorinating agent in the presence of a tertiary base to give an imide-chloride-groupcontaining compound of Formula III: wherein A is the esterifying group, reacting this compound with a metal carboxylate of Formula IV: where M is a metal atom and B is a protected amino group, to give a diacylpenicillin ester of Formula V: and subjecting this compound to dephenylacylation, de-esterification and elimination of the amino -protective group. Suitable esterifying groups are benzyl, pnitrobenzyl, phenacyl or p-bromophenacyl groups. The ester is reacted with PCl 5 in the presence of pyridine to give the compound III. Theα-amino group of the metal carboxylate IV is protected by, e.g., carbobenzoxy, p-nitrocarbobenzoxy, carboaryloxy, p - toluenesulphonyl, trityl, benzyl, dibenzyl, benzylsulphonyl, o - nitrophenylsulphonyl, trifluoroacetyl, chloroacetyl, formyl or o-nitrophenoxyacetyl. The protective group is removed in the final stage of the process by, e.g., reaction with trifluoracetic or dichloracetic acid or by catalytic reduction. The dephenylacetylation of the compound V is effected by aminolysis or by reaction with a metal thiophenolate or halothiophenolate. Aminolysing agents may be primary or secondary organic amines, ammonia or an N,N-disubstituted aminoalkylamine. The use of a metal thiophenolate or halothiophenolate can bring about simultaneous de-esterification in which case it is used in excess of the compound V, e.g. 2-4 moles per mole of compound V. If used in about equimolar proportions, however, only the dephenylacetylation step is effected. Suitable reagents are sodium or potassium thio- or p-chlorothio-phenolate. If necessary, de-esterification is then carried out, e.g. by catalytic reduction or reaction with a metal thiophenolate or halothiophenolate, to give the desired ampicillin.</p> |
