ES416646A2 - Antibiotics - Google Patents

Abstract

Improvements introduced in the object of the main patent No. 399,267, applied for on January 28, 1972, for "A process for the preparation of cephalosporin compounds", said improvements referring to a process for the preparation of a compound selected from the group consisting of from: (a) 7β-acylamido-3-acetoxymethyl cef-3-em-4-carboxylic acids (sin isomers) in which the acylamido group in position 7β is 2-hydroxyimino-2- (thien-3-yl) acetamido; 2-hydroxyimino-2- (furyl) acetamido; 2-ethoxycarbonyloxyimino-2- (thien-2-yl) acetamido; 2-acetoxyimino-2- (thien-2-yl) acetide; 2- (2-chloroethylcarbamoyloxyimino) -2- (thien-2-yl) acetamido; or 2-hydroxyimino (pyrid-4-yl) -acetamido; (b) 3-substituted methyl-7β- [2-hydroxyimino-2- (thien-2-yl) acetamido] cef-3-em-4-carboxylic acids (sin isomers) in which the group at position 3 is acetylthiomethyl, crotonyloxymethyl, 1-phenyltetrazol-5-ylthiomethyl, 1-methyltetrazol-5-ylthiomethyl, or 5-phenyl-1,3,4-oxadiazol-2-ylthiomethyl; (c) 3-substituted methyl-7β- [2-hydroxyimino-2- (furyl) -acetamido] cef-3-em-4-carboxylic acids (sin isomers) in which the group in position 3 is 4-carbamoylpyridinium -methyl, 1-methyltetrazol-5-ylthiomethyl or 5-methyl-1,3,4-thiadiazol-2-ylthiomethyl and (d) 6β-acylamido-2,2-dimethylpenam-3-α-carboxylic acids (s in isomers) in which the acylamido group in the 6β position is 2-hydroxyimino (thienyl) acetamido, or 2-hydroxyimino-2- (furyl) acetamido, and its non-toxic derivatives, said compounds having the formula ** (See formula) ** [where Rα X have appropriate meanings corresponding to those encompassed by (a) - (d) above] comprising either (A) condensing a compound of formula ** (See formula) ** (where B is >S or >S→O, X has the previously defined meaning, R1 is hydrogen or a carboxyl group blocking group, and the dashed line bridging positions 2, 3 and 4 of formula (IIa) indicates that the compound can be a cef-2-em compound or a cef-3-em compound), with an acylating agent which is the non-corresponding isomer of the acid ** (See formula) ** (where Rα has the meanings indicated above) or with an acylating agent corresponding to an acid which is a precursor of acid (III) and converting the acyl group precursor resulting in the desired acyl group; or (B) react a compound of formula ** (See formula) ** (where B, X, R1 and the dashed line have the meanings indicated above, provided R1 is not hydrogen), with an acid of formula (III) that does not contain a free hydroxyimino group; or (C) reacting a compound of formula ** (See formula) ** (where Acyl is the group R or a precursor thereof; B, R1 and the dashed line have the meanings indicated above and X is a replaceable residue of a nucleophile), with a nucleophile, after which, if necessary and in each case is desired, any of the following reactions (D) are carried out: (i) conversion of a precursor of the desired Rα group into said group, (ii) conversion of an Δ 2 isomer to the isomer Δ 3 desired, (iii) removal of any of the carboxyl group blocking groups, (iv) reducing a compound in which Z is >S→O to form the desired compound Z => S, and (E) recovering the desired compound of formula (I), if necessary, then of the separation of the isomers. (Machine-translation by Google Translate, not legally binding)