DE2611645A1 - (2)-Amino-(2)-acyloxyphenyl-acetamido cephalosporins - for use as antibacterial agents - Google Patents

Abstract

New cephalosporins of formula (I) and their esters and salts: In the formula R is H, 1-9C alkyl opt. substd. by F, Cl, Br, COOH, 1-5C alkoxy, 1-4C alkanoyloxy or 2-5C alkoxycarbonyl, or 1-10C alkoxy opt. substd. by F, Cl, Br, 1-5C alkoxy, 1-4C alkanoyloxy or 2-5C alkoxycarbonyl; R1 is H, acetoxy or S-Het; Het is 1,2,3-triazol-5-yl, 1-methyltetrazol-5-, 1,3,4-thiadiazol-2-yl or 2-methyl-1,3,4-thiazdiazol-5-yl. Cpds. (I) are broad-spectrum antibacterials, e.g. orally effective against Staph. aureus infections at a daily dose of 10-60 mg/kg. A typical cpd. is 7- D-2-amino-2-(3-propionyloxyphenyl) acetamido -3-methyl-3-cephem-4-carboxylic acid, which may be prepd. from 7- D-2-t-butyloxycarbonylamino-2-(3-hydroxyphenyl)acetamido -3-me- thyl-3-cephem-4-carboxylic acid.

Description

Cephem Derivatives and Processes

for their preparation The invention relates to new cephem derivatives of the general formula I. wherein RH, alkyl with 1-9 carbon atoms or substituted one or more times by F, Cl, Br, C00H, alkoxy with 1-4 atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2-5 carbon atoms Alkyl with 1-9 carbon atoms, alkoxy with 1-10 carbon atoms or one or more times with F, Cl, Br, alkoxy with 1-4 carbon atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2 - 5 carbon atoms substituted alkoxy with 1 - 10 carbon atoms, R1 H, acetoxy or -S - Het, and Het 1,2,3-triazol-5-yl, 1-methyltetrazol-5-yl, 1, Means 3,4-thiadiazol-2-yl or 2-methyl-1,3,4-thiadiazol-5-yl, as well as their easily cleavable esters and their physiologically acceptable salts.

The invention was based on the object of finding new compounds that can be used to manufacture drugs. This task was solved by providing the compounds of formula I.

It has been found that these compounds are excellent especially in vivo Have antibacterial effectiveness against gram-negative and against gram-positive germs. In comparison with known semisynthetically obtained cephalosporins, they show clear differences with regard to the sensitivity of the individual germs. In In numerous cases, known cephalosporins are significantly affected by new products surpassed, making them crucial in fighting certain bacterial infections possess therapeutic benefits. It should be emphasized that the connections of the formula I have excellent antibacterial effectiveness when administered orally show, for example in mice against Staphylococcus aureaus (measured as-DC 50).

The compounds can accordingly be used as medicaments, in particular used to fight bacterial infections. They can also be saved as Intermediate products can be used to manufacture other drugs.

The invention thus relates to the new compounds of the formula I as well as their easily cleavable esters and their physiologically harmless salts.

Preferred radicals R are hydrogen, unsubstituted alkyl with 1 - 9 atoms, especially unsubstituted alkyl with 1 - 6 atoms, but above all unsubstituted and unbranched alkyl with 1 to 6 atoms. Besides are also those simply by fluorine, chlorine, bromine, alkoxy with 1 - 4 Ç atoms or carboalkoxy with 1-5 carbon atoms, substituted alkyls with 1-9 carbon atoms are preferred. Particularly what is important here are those simply due to chlorine. Alkoxy with 1 - 2 carbon atoms or through Carboalkoxy with 2 - 3 atoms, substituted alkyls with 1 - 6 atoms, especially when the alkyl radicals are unbranched. R is also alkoxy with 1 - 10 atoms, preferably with 1-6 atoms, in particular unbranched alkoxy with 1-6 atoms; these alkoxy radicals can be multiply preferably but simply by fluorine, chlorine, Bromine, alkoxy with 1 - 4 atoms, alkanyloxy with 1 - 4 carbon atoms or carboalkoxy with 1 - 5 carbon atoms may be substituted. Particularly preferred are those simply by chlorine, Alkoxy with 1 - 2 atoms, alkanyloxy with 1 - 2 carbon atoms or carboalkoxy with 2 - 3 carbon atoms substituted alkoxy radicals with 1 - 6 atoms. In addition, R can also an alkyl radical with 1 that is monosubstituted by alkanyloxy with 1 - 4 carbon atoms - 9 atoms, preferably 1-6 carbon atoms, which are in particular unbranched is. If R is a polysubstituted alkyl or alkoxy radical, so the radicals with 1-6 carbon atoms are again preferred, especially when they are unbranched. In the case of polysubstituted radicals R, they are doubly by chlorine or bromine-substituted radicals are particularly important. In detail, the following are preferred Rests mentioned by way of example: hydrogen, methyl, ethyl, propyl, isopropyl, butyl, Isopropyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, Octyl, nonyl; 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-fluoropropyl, 2-chloropropyl, 2-bromopropyl, 2-fluorobutyl, 2-chlorobutyl, 2-bromobutyl, 2-fluoropentyl, 2-chloropentyl, 2-bromopentyl, 2-fluorohexyl, 2-chlorohexyl, 2-bromohexyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, 5-fluoropentyl, 5-chloropentyl, 5-bromopentyl, 6-fluorohexyl, 6-chlorohexyl, 6-bromohexyl; Methoxymethyl, Ethoxymethyl, propyloxymethyl, butyloxymethyl, tert-butyloxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-methoxypropyl, 2-ethoxypropyl, 2-methoxybutyl, 2-ethoxybutyl, 2-methoxypentyl, 2-ethoxypentyl, 2-methoxyhexyl, 2-ethoxyhexyl, 3-methoxypropyl, 3-ethoxypropyl, 4-methoxybutyl, 4-ethoxybutyl, 5-methoxypentyl, 5-ethoxypentyl, 6-methoxyhexyl, 6-ethoxyhexyl; Acetoxymethyl, 2-acetoxyethyl, 2-acetoxypropyl, 2-acetoxybutyl, 2-acetoxypentyl, 2-acetoxyhexyl, 3-acetoxypropyl, 4-acetoxybutyl, 5-acetoxypentyl, 6-acetoxyhexyl; Methoxycarbonylmethyl, 2-methoxycarbonylethyl, 2-methoxycarbonylpropyl, 2-methoxycarbonylbutyl, 2-methoxycarbonylpentyl, 2-methoxycarbonylhexyl, ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-ethoxycarbonylpropyl, 2-ethoxycarbonylbuty1, 2-ethoxycarbonylpentyl, 2-ethoxycarbonylhexyl, 3-methoxycarbonylpropyl, 3-ethoxycarbonylpropyl, 4-methoxycarbonylbutyl, 4-ethoxycarbonylbutyl, 5-methoxycarbonylpentyl, 5-ethoxycarbonylpentyl, 6-methoxycarbonylhexyl, 6-ethoxyearbonylhexyl; Dichloromethyl, trichloromethyl, dibromomethyl, 2,3-dichloropropyl, 2,3-dibromopropyl, 2,3-dichlorobutyl, 2,3-dibromobutyl, 3,4-dichlorobutyl, 3,4-dibromobutyl; Hydroxycarbonylmethyl, 2-hydroxycarbonylethyl, 3-hydroxycarbonylpropyl, 4-hydroxycarbonylbutyl, 5-hydroxycarbonylpentyl, 6-hydroxycarbonylhexyl; Methoxy, ethoxy, propoxy, isopropoxy, butyloxy, sec. -Butyloxy, Isobutyloxy, tert-butyloxy, Pentyloxy, hexyloxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-fluoropropyloxy, 2-chloropropyloxy, 2-bromopropyloxy, 2-fluorobutyloxy, 2-chlorobutyloxy, 2-bromobutyloxy, 2-fluoropentyloxy, 2-chloropentyloxy, 2-brompentyloxy, 2-fluorohexyloxy, 2-chlorohexyloxy, 2-bromohexyloxy, 3-chloropropyloxy, 4-chlorobutyloxy, 5-chloropentyloxy, 6-chlorhexyloxy, 2,2-dichloroethyloxy, 2,2,2-trichloroethoxy, 2,3-dichloropropyloxy, 2,3-dichlorobutyloxy, 3, 4-dichlorobutyloxy; Methoxymethoxy, Ethoxymethoxy, propyloxymethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, 2-methoxypropyloxy, 2-ethoxypropyloxy, 2-propyloxypropyloxy, 3-methoxypropyloxy, 3-ethoxypropyloxy, 4-methoxybutyloxy, 4-ethoxybutyloxy, 5-methoxypentyloxy, 5-ethoxypentyloxy, 6-methoxyhexyloxy, 6-ethoxyhexyloxy; 2-formyloxyethoxy, 2-acetoxyethoxy, 3-formyloxypropyloxy, 3-acetoxypropyloxy, 4-formyloxybutyloxy, 4-acetoxybutyloxy, 5-acetoxypentyloxy, 6-acetoxyhexyloxy; Methoxycarbonylmethoxy, Ethoxycarbonylmethoxy, 2-methoxycarbonylethoxy, 2-ethoxycarbonylethoxy, 3-methoxycarbonylpropyloxy, 3-ethoxycarbonylpropyloxy, 4-methoxycarbonylbutyloxy, 4-ethoxycarbonylbutyloxy, 5-methoxycarbonylpentyloxy, 5-ethoxycarbonylpentyloxy, 6-methoxycarbonylhexyloxy, 6-ethoxycarbonylhexyloxy.

R1 is preferably acetoxy or S-het. Acetyl is particularly preferred; if R1 denotes S-Het, then these are 1-methyl-tetrazolyl-5-mercapto and 1,3,4-thiadiazolyl-2-mercapto radicals preferred; in addition, R1 can also be 1,2,3-triazolyl-5-mercapto or 2-methyl-1,3,4-thiadiazolyl-5-mercapto mean. In addition, R1 can also be hydrogen.

Easily cleavable esters of the compounds of the formula I are in first and foremost the tert-butyl esters mentioned, also for example the trimethylsilyl, Benzyl, benzhydryl, trichloroethyl, benzylmethyl, p-methoxybenzyl or methoxymethyl esters, also especially alkanoyloxymethyl esters, such as the acetoxymethyl and pivaloyloxymethyl esters.

Those compounds of the formula I are preferred in which at least one of the symbols R and R1 has one of the preferred meanings given above Has.

Some of these preferred groups of compounds can be identified by the the following sub-formulas Ia to Iy are reproduced, which otherwise correspond to the formula I. correspond, and in which the unspecified symbols in formula I have given meaning, in which, however, in Ia R denotes alkyl having 1-9 carbon atoms; in Ib R denotes alkyl having 1 to 6 carbon atoms; in Ic R unbranched alkyl with 1 - 6 Means carbon atoms; in Ie R is 2-chloroalkyl with 2-6 carbon atoms; in If R is 2-methoxyalkyl or 2-ethoxyalkyl with 2 to 6 carbon atoms in each case in the alkyl radical; in Ig R # methoxyalkyl or # is -ethoxyalkyl with in each case 3 - 6 carbon atoms in the alkyl radical; in Ih R 2-acetoxyalkyl with 2 - 6 carbon atoms in the alkyl radical; in Ii R 4 -acetoxyalkyl with 3 - 6 carbon atoms in the alkyl radical; in Ij R bJ-methoxycarbonylalkyl or CO -ethoxycarbonylalkyl each having 1 - 6 carbon atoms in the alkyl radical; in Ik R alkoxy with 1 - 10 carbon atoms means; in II R means alkoxy with 1-6 carbon atoms in Im R means methoxyalkoxy or C-ethoxyalkoxy each having 1 - 6 carbon atoms in the alkoxy radical; in In R denotes t-acetoxyalkoxy with 1-6 carbon atoms in the alkoxy radical; in Io R CO -methoxycarbonylalkoxy or # -ethoxycarbonylalkoxy each having 1 - 6 carbon atoms in the alkoxy radical; in Ip R1 is -S-Het or acetoxy; in Iq R1 is acetoxy; in Ir R alkyl with 1 - 6 carbon atoms and R1 are -S-Het or acetoxy; in Is R alkoxy with 1 - 6 C atoms and R1 are -S-Het or acetoxy; in It R 2-chloroalkyl with 1 to 6 carbon atoms and R1 is -S-Het or acetoxy; in Iu R # -ethoxyalkyl or # -ethoxyalkoxy with 1 - 6 carbon atoms in each case in the alkyl or alkoxy radical, and R1 -S-Het or acetoxy mean; in Iv R # -ethoxycarbonylalkyl or # -ethoxycarbonylalkoxy with each 1-6 carbon atoms in the alkyl or alkoxy radical, and R1 is -S-Het or acetoxy; in Iw R are unbranched alkyl with 1-6 carbon atoms and R1 is -S-Het or acetoxy, in Ix R1 1,2,3-triazolyl-5-mercapto, -methyltetrazolyl-5-mercapto, 1,3,4-thiadiazolyl-2-mercapto or is 2-methyl-1,3,4-thiadiazolyl-5-mercapto; in Iy R unbranched alkyl with 1 - 6 carbon atoms or unbranched alkoxy with 1 - 6 carbon atoms and R¹ 1-methyl-1,2,3,4-tetrazolyl-5-mercapto- or 1,3,4-thiadiazolyl-2-mercapto.

The invention also relates to a process for the preparation of the compounds of the formula I and their easily cleavable esters and their physiologically acceptable salts, which is characterized in that a compound of the general formula II where R1 has the meaning given above, or one of its functional derivatives with a compound of the general formula III RCOO-m-C6H4-CH (NH2) COOH III where R has the meaning given above, or one of its functional derivatives or an acid addition salt di. it converts its compounds, or that a compound of the general formula IV wherein R2 is alkenyl with 2-9 carbon atoms or mono- or polysubstituted by F, Cl, Br, COOH, alkoxy with 1-4 atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2-5 carbon atoms with 2 - 9 atoms, alkenyloxy with 2 - 10 carbon atoms or one or more times with F, Cl, Br, alkoxy with 1 - 4 atoms, alkanoyloxy with 1 - 4 carbon atoms or carboalkoxy with 2 - 5 carbon atoms Substituted alkenyloxy with 2-10 carbon atoms and R1 has the meaning given above, is reacted with a hydrogenating agent or with chlorine or bromine, or in a compound which otherwise corresponds to formula I, but in which an NH2 group is present in a functionally modified form, or one of its easily cleavable esters or one of its physiologically tolerable salts, this NH2 group is set free by treatment with hydrolyzing or hydrogenolyzing agents, and / or in a compound of formula I or one of its easily obtained cleavable esters or one of their Physiologically acceptable salts convert a radical R1 into another radical R1 by reaction with reducing or hydrogenolysing agents or by reaction with a thiol HS-Het and / or that one in a compound of formula I obtained or one of its easily cleavable esters or one of its physiologically harmless salts converts the radical R into another radical R by reacting with alkylating or solvolyzing agents and / or converting a compound of the formula I into one of its easily cleavable esters by reacting with an esterifying agent, and / or converting a compound of the Formula I is set free from one of its easily cleavable esters by reaction with a hydrolyzing agent and / or that a compound of the formula I is converted into one of its physiologically acceptable salts by reaction with an acid or a base and / or that a compound of formula I by reacting with a base or an acid au s releases one of its salts.

The a-C atom of the substituted phenylacetyl radical, which is the side chain in a compound of formula I is asymmetric. The invention covers hence pure epimers in which this carbon atom has the D configuration and such pure epimers in which this carbon atom has the L configuration. But also the epimer mixtures of the formula I, in which the a-carbon atom of the side chain is partly D- and partly L-configured is, are the subject of the invention.

Those epimer mixtures are preferred in which the D- and the L-configuration occur in approximately equal parts. Such compounds are particularly preferred of the formula I, in particular of the formulas Ia to Iy, in which the a-C atom of the side chain has the D configuration.

The processes for making the compounds of Formula I are in progress according to methods as they are known in cephalosporin chemistry and in the literature are described in more detail.

The invention also relates to pharmaceutical preparations, which by a content of at least one compound of the general formula I and / or one of their physiologically harmless salts and / or one of their easy cleavable esters are labeled.

The invention also relates to the use of a compound of the formula I or one of their physiologically acceptable salts or one of their easily cleavable ester for the production of pharmaceutical preparations.

Finally, the invention also relates to a method for production of pharmaceutical preparations, characterized in that a compound of the formula I and / or one of its physiologically acceptable salts and / or one their easily cleavable esters, optionally together with at least one solid, liquid or semi-liquid auxiliary or carrier materials and if necessary together with at least one further active ingredient in a suitable dosage form brings.

The starting materials for the process according to the invention are partly known, partly new. You can by methods known per se analogously to known ones Connections are made. For example, the acids of the formula II (R1 = -S-Het) obtainable from 7-aminocephalosporanic acid (7-ACS; II, R1 = -OCOCH3) by Reaction with the known heerocyclic thiols of the formula Het-SH, or the associated metal mercaptides, e.g. through reaction of the corresponding alkali metal salts in hot, aqueous acetone.

Suitable functional derivatives of an acid of the formula II are in primarily the easily cleavable esters, e.g. the tert-butyl esters, the trimethylsilyl esters (such as arise in situ from II and N-trimethylsilyl acetamide) and the others easily cleavable esters given above. Furthermore, the salts, especially the neutral salts of these acids.

The alkali metal (e.g. sodium, potassium), Alkaline earth metal (e.g. magnesium, calcium) and ammonium salts. Among the latter are those of amines, especially of tertiary amines, e.g. triethylamine, triethanolamine, Pyridine, collidine, derived salts are preferred. These salts can be used as such in be used in the reaction; you can also in situ from an acid II and a base, e.g. NaHCO3, Na2HP04 or triethylamine.

The acids of the formula III are derived from 2- (m-hydroxyphenyl) glycine. They are obtained from this known compound after blocking the amino group with one of the protective groups customary in peptide chemistry by Reaction with an acid of the formula V RCOOH V in which R has the meaning given above has, or an activated derivative of this acid.

The activated derivatives of the acids V are particularly suitable Halides, preferably the chlorides and bromides, also the anhydrides and mixed Anhydrides as well as azides and activated esters, e.g. those with p-nitrophenol, 2,4-dinitrophenol, p-nitrophenyl mercaptan, methylene cyanohydrin or N-hydroxysuccinimide. As mixed Anhydrides of the acids V are e.g. on the one hand those with lower alkanoic acids, especially with acetic acid or substituted acetic acids, e.g.

Trichloroacetic acid, pivalic acid or cyanoacetic acid and on the other hand Anhydrides with carbonic acid half-esters, which e.g. by reacting the acids V with chloroformic acid benzyl ester, -p-üitrobenzylester, -isobutylester, -äthylester and -allylester are available. All of these functional derivatives of V are preferably generated in situ.

The e.g. for the preparation of the starting compounds of the formula III important compounds of the formula V are known. These are fatty acids with 1-10 carbon atoms, preferably with 1-7 atoms, which are in particular unbranched are and are one or more, but preferably simply by F, Cl, Br, alkoxy with 1 - 4 atoms, preferably methoxy or ethoxy, or alkanoyloxy with 1 - 4 atoms, preferably acetoxy can be substituted. These substituents are mainly in the ß-position or in the W-position.

Preferred acids of the formula V are also α, G -alkanedicarboxylic acids with 2-11 atoms, preferably with 2-8 atoms, in particular succinic acid, glutaric acid and adipic acid (the most important activated derivatives of bemstem and glutaric acid are their cyclic anhydrides).

Other important compounds of the formula V are the a, OJ-dicarboxylic acid monoalkyl esters, the alkyl radical preferably having between 1 and 4 carbon atoms. Particularly important are the monomethyl and monoethyl esters of alkanedicarboxylic acids with 3-11 atoms, preferably with 4-6 atoms, especially of succinic, glutaric and adipic acid. The activated derivatives of the dicarboxylic acid of the formula V are usually found only one carboxyl group in activated form. In general, the implementation takes place of 2- (m-hydroxyphenyl) -glycine (with the amino group in protected form, for example present as tert-butoxycarbonylamino or 2-ethoxycarbonyl-1-methylvinylamino group) with a compound of the formula V (or with their activated derivatives) in the presence an inert solvent.

Particularly suitable solvents are chlorinated hydrocarbons, z. B. methylene chloride, chloroform; Ethers such as diethyl ether, tetrahydrofuran, dioxane; Ketones such as acetone, butanone; Amides such as dimethylformamide (DMF), dimethylacetamide, Hexamethylphosphoric acid triamide (HMPT); Sulfoxides such as dimethyl sulfoxide (DMSO); Water; also organic or aqueous inorganic bases. Mixtures of the mentioned solvents are used. The reaction temperatures are between about -70 and about +800, preferably between -50 and +300, in particular between -40 and 100. The reaction time depends on the nature of the selected starting materials and the reaction temperature dependent; it is usually between 5 minutes and 72 hours.

If a compound of the formula II or one of its functional ones is used Derivatives with an activated derivative of the formula III, this is activated Derivative always as an acid addition salt, with the proton as the amino blocking group serves and prevents self-acylation.

At this point it should be noted that "functional derivative can mean both a compound in which a functional group in such a way Protected form exists that this group is not in a certain reaction bothersome, as well as a connection in which a certain functional Group is present in activated form, the more so in the desired reaction respond well. Of course, both functional modifications can also be used be present at the same time, for example in the reactions of interest here an amino acid can be used as an activated acid derivative, the amino group blocked by a protecting group.

The acid addition salts of the compounds of the formula III are especially those with strong acids, preferably with strong mineral acids like HCl, HBr, HJ, H2S04 or HN03> but also with strong organic acids, for example trichloroacetic acid or trifluoroacetic acid.

It is particularly advantageous to acylate a compound of the Formula II or one of its functional derivatives is the acid chloride hydrochloride to use a compound of formula III.

The implementation of the cephem derivatives II (or their functional derivatives) with the compounds of the formula III (or

with their functional new derivatives) usually takes place in the present an inert solvent Implementation of a compound of Formula II with a compound of the formula III (or one of its activated derivatives) usually takes place under reaction conditions which are the same as those for the acylation above of 2- (m-hydroxyphenyl) glycine. Particularly preferred reaction temperatures are between -40 and +100. Here, too, the reaction time depends on the type selected Starting materials and the reaction temperature dependent and is approximately between 10 minutes and 80 hours. Suitable solvents are those above for the acylation of 2- (m-hydroxyphenyl) -glycine with a compound of the formula V or the activated derivatives thereof.

The acylation of a 7-amino group of a cephalosporin is a known implementation and any functional equivalent of a compound of formula III, usually used as an acylating agent for primary amino groups can be used. Examples of suitable acylating derivatives (= activated derivatives) of the free Acids have already been mentioned. The free acid can with a compound of the Formula II or one of its easily cleavable esters can be coupled when you first the free acid has reacted with N, N'-trimethylchloroformiminium chloride, or by the use of enzymes or an N, N'-carbonyldiimidazole or an N, N'-carbonylditriazole or an Oarbodiimide reagent, e.g.

N, N'-diisopropylcarbodiimide, N, N'-dicyclohexylcarbodiimide or N-cyclohexyl-N '- (2-morpholinoethyl) -carbodiimide or with the help of an isoxazolium salt.

Another activated derivative is a corresponding azolide, i. an amide of the corresponding acid, whose amide nitrogen is a member of a quasi-aromatic 5-membered ring containing at least two nitrogen atoms, e.g. one Imidazole, pyrazole, triazole, benzimidazole or benzotriazole ring. Another suitable derivative the substituted phenylglycic acid of the formula III is the N-carboxyanhydride (Leuchs' anhydride) the group that serves the carboxyl group also activated to protect the amino group.

In particular, it is particularly useful to have an easily split Ester, preferably a tert-butyl ester of acid II with a compound of Formula III, in which the amino group is present in protected form, to implement, wherein one advantageously adds a water-binding agent and then in the obtained Reaction product releases the amino group hydrolytically or hydrogenolytically. as Water-binding agents are e.g. carbodiimides.

especially dicyclohexylcarbodiimide (DCC).

For example, 7-ACS-tert-butyl ester, a compound of the formula VI RCOO-m-C6H4-CH (NHR3) COOH VI where R3 has a hydrolyzing or hydrogenolyzing Means removable protective group and R has the meaning given above, and DCC in approximately equimolar proportions and with cooling in an inert solvent react, especially in chlorinated hydrocarbons such as methylene chloride or in aprotic dipolar solvents such as DMF or DMSO or in solvent mixtures.

The implementation of a compound of formula II or one of its functional ones Derivatives with activated derivatives (or their salts) of the acids III are preferred made in the presence of a basic catalyst.

Suitable basic catalysts are inorganic metal hydroxides, preferably alkali metal or alkaline earth metal hydroxides, basic salts, as well as organic amines, preferably tertiary organic amines. Used in particular one NaHC03, KHCOD, Nu2003, K2003, NaOH, KOH, pyridine or a base of low nucleophilicity, e.g. a tertiary amine such as triethylamine, N-methylmorpholine, ethyldiisopropylamine or potassium tert. butoxide.

The radical R3 means hydrolytically or hydrogenolytically easy Removable protective group as it is known in particular from peptide chemistry. In particular, the following protective groups come into question: Arylmethoxycarbonyl radicals, such as benzyloxycarbonyl, Alkyloxycarbonyl, such as tert-butyloxycarbonyl (B00); Arylsulfonyl radicals, such as p-bromophenylsulfonyl or p-tolylsulfonyl; Arylmethyl radicals such as benzyl, diphenylmethyl or triphenylmethyl; Acyl groups, preferably alkanoyl groups such as formyl, acetyl or pivaloyl or substituted alkanoyl groups such as trifluoroacetyl, chloroacetyl or o-nitrophenoxyacetyl; Aryloxycarbonyl groups such as phenoxycarbonyl; Alkylthiocarbonyl or aralkylthiocarbonyl radicals, such as benzyithiocarbonyl or activated vinyl groups such as 2-ethoxywarbonyl-1-methylvinyl.

For a further variant of the preparation of the compounds of the formula I important compounds of the formula IV are from the cephem derivatives of the formula II or their functional derivatives by reacting with compounds of the formula VII R2 R2COO-m-C6H4-CH (NH2) COOH VII in which R2 has the meaning given above, or one of their functional derivatives or an acid addition salt of these compounds obtainable, the reaction conditions being the same as above for the reaction of a compound of the formula II described with a compound of the formula III correspond.

The compounds of the formula VII are known or can be used analogously Method as described above for the compounds of the formula III from 2- (m-hydroxyphenyl) glycine or a functional derivative of this compound and an acid of the formula VIII R2COOH VIII in which R2 has the meaning given above, or an activated derivative this acid can be produced.

In the above formulas IV, VII and VIII, R2 denotes an alkenyl radical with 2 - 9 carbon atoms or an alkenyloxy radical with 2 - 10 carbon atoms with the above Substitution possibilities, whereby these radicals are preferably monounsaturated, but can also be polyunsaturated. Those unsaturated are preferred Radicals which are derived from the preferred radicals R mentioned above and differs from these only through the presence of a C = C double bond differentiate. The following radicals R2 are particularly important: vinyl, 2-methylvinyl, 2-hydroxycarbonyl vinyl, 2-ethoxycarbonyl vinyl and allyl.

The compounds of formula IV can by treating with a hydrogenating Means, preferably with catalytically activated oxygen in the presence of a noble metal catalyst, such as platinum or platinum oxide, which are also applied to a suitable carrier material can be, or in the presence of a Raney metal, such as Raney nickel or Raney cobalt, are hydrogenated to give the desired compounds of formula I. The hydrogenation will in a suitable inert solvent, for example in ethyl acetate, preferably carried out at room temperature and at pressures of about 1 atmosphere. One breaks the hydrogenation after absorption of 1 mol of hydrogen from in order to avoid unwanted further hydrogenations, for example the double bonds in the cephem system or in the phenyl ring.

It is also possible by adding chlorine or bromine to the double bond in R2 to prepare the compounds of the formula I from the compounds of the formula IV. It usually works in inert solvents, for example halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, chlorobenzene, bromobenzene or perchlorobutadiene, preferably at temperatures between +50 and +400, in particular at room temperature. It is advisable to add the halogen in equimolar amounts, to avoid unwanted attachment, for example to the double bond of the cephem system, to avoid.

The cephem derivatives of the formula I are also available by a functionally contained in a compound otherwise corresponding to formula I sets modified NH2 group according to known methods in freedom.

The starting materials for this process variant can be obtained, for example, by reacting a compound of the formula II with a compound of the formula VI. It is particularly advantageous to react a compound of the formula II or one of its functional derivatives with a compound of the formula IX HO-m-C6H4-CH (NHR3) COOH IX in which R3 has the meaning given above, or one of its functional derivatives under reaction conditions, as already described above for the reaction of a compound of the formula II or one of its functional derivatives with a compound of the formula III or one of its functional derivatives, and the compounds of the formula X obtained in which R1 and R3 have the meanings given above, or to react their functional derivatives or the salts of these compounds further with an acid of the formula V or an activated derivative of this acid.

A functionally modified amino group can according to known Methods described in the literature are solvolytic, especially hydrolytic or set free by hydrogenolysis. A solvolysis, preferably one Hydrolysis, in particular also of a tert-butyloxycarbonylamino group, is e.g. with trifluoroacetic acid or with aqueous mineral acids, e.g. hydrochloric acid Temperatures carried out between -10 ° and 50q. Hydrogenolysis, especially cleavage of benzyl, tert. -Butoxycarbonyl and carbobenzyloxy radicals are possible by hydrogenation in the presence of noble metal catalysts such as 5 to 50% palladium on carbon or palladium oxide. It is expedient to hydrogenolyze at temperatures between -10 and +500, especially at room temperature, and at pressures between 1 and 10 at, preferably at normal pressure. Particularly mild hydrogenation conditions have to be chosen to undesired reductions, for example the C = C double bond of the cephem system to avoid.

You can also in a compound of formula I obtained or a their easily cleavable esters or one of their phy.mnlogically harmless salts the radical R by reaction with alkylating agents or solvolyzing agents convert to another remainder R. Alkylating agents are particularly useful with such Compounds of formula I implemented in which R contains a free COOH group. Particularly suitable alkylating agents are alkanols with 1 to 4 atoms, such as Methanol, ethanol, propanol, butanol, isopropyl alcohol, sec-butyl alcohol, isobutyl alcohol and tert-butyl alcohol, or acid esters, especially carboxylic acid esters, in particular Alkanoic acid esters, e.g. the formates, acetates, propionates, pivaloylates of the named Alcohols. Also the alkyl halides derived from the alcohols mentioned with 1-4 atoms, especially bromides, are suitable alkylating agents.

The reaction of a compound of the formula I obtained with an alkylating one The agent is usually carried out in the presence of an acidic catalyst, preferably a mineral acid such as HCl, HBr or H2S04, or an organic acid especially a sulfonic acid such as p-toluenesulfonic acid.

It is advantageous for the alkylation in the presence of a dehydrating agent To work by means of DCC or by forming water by azeotropic distillation to be removed if the alkylating agent is an alcohol with 1 - 4 carbon atoms. As a rule, one works in inert solvents, e.g. hydrocarbons such as benzene or chlorinated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride or 1,2-dichloroethane using an excess of the alkylating agent. It is also possible to use the alkylating agent as a solvent at the same time. If alkyl halides with 1 to 4 carbon atoms are used as alkylating agents, then if the carboxyl group in the radical R is preferably in salt form in the alkylation, mainly as silver salt. The alkylation temperatures are between 0 and 1000. Other alkylating agents are diazoalkanes with 1-4 atoms, in particular Diazomethane. It is expedient to alkylate with these compounds in ethers such as diethyl ether or dioxane, preferably at temperatures between 0 and 400, in particular at Room temperature.

With the solvolyzing agents, with those in a received compound of the formula I the radical R can be converted into another radical R is they are primarily hydrolyzing agents. There are above all in question Water in the presence of a base, preferably an inorganic base, in particular an alkali metal hydroxide or carbonate, such as NaOH, KOH, Na2C03 or K2C03, but also an organic base such as triethylamine, triethanolamine, or piperidine. Besides If inert organic solvents can still be present, the procedure is preferred in mixtures of dioxane, acetone or dimethylformamide and water as the reaction medium. The solvolysis temperatures are generally between 100 and 800, preferably at room temperature.

If desired, you can in the resulting product of the formula I or one of its easily cleavable esters or one of its physiologically harmless ones Salts exchange one residue R1 for another residue R1.

It is particularly advantageous to use a cephalosporanic acid obtained Formula I (R1 = OCOCH) by reaction with a mercaptan of the formula Het-SH in the corresponding thioether (R1 = -SHet) to convert. A salt is expediently used of cephalosporanic acid with a salt of thiol in aqueous acetone at temperatures between 20 and 1000 and pH values between 4 and 8 µm. Particularly suitable salts are the alkali metal, especially the sodium salts. This synthetic route is particularly suitable for the preparation of compounds of the formula I in which the radical R neither through a carboxyl group is still substituted by an alkoxycarbonyl or acyloxy group is.

You can also catalytically an acetoxy radical R1 by treatment activated hydrogen, for example among those mentioned above for hydrogenolysis Convert reaction conditions into a hydrogen atom.

As already explained, the compounds of formula I have in the with the side chain linked to the ß-lactam ring a center of asymmetry.

They are therefore mostly obtained as a mixture of two epimeric forms, which due to their different physical properties from the mixture can be isolated and obtained in pure form, for example by recrystallization from suitable solvents (in particular, instead of the compounds themselves well-crystallizing derivatives can be used), but in particular also with the aid of chromatographic methods, both adsorption chromatographic or partition chromatographic methods as well as mixed forms come into question.

It is of course also possible to use pure diasteromeric compounds of the formula I by the methods described, for example by adding compounds of the formula III (or their activated derivatives) used as starting materials, the are already optically active.

The optically active compounds of the formula III or

their activated derivatives can by a variety of known methods, as described in the literature, especially for the cleavage of racemic α-amino acids are given, can be prepared from the racemates.

The chemical separation method is preferred.

Then from the racemic mixture by reaction with a optically active auxiliary formed diastereomers. So, if necessary, you can use a react optically active base with the carboxyl group of a compound of formula III. For example, one can use diastereomeric salts of the compounds of formula III with optically active amines such as quinine, brucine, morphine or 1-phenylethylamine.

The amino group can be reacted with an optically active acid such as (+) - and (-) - tartaric acid, camphoric acid or ß-camphorsulphonic acid for the formation of more suitable diastereomeric salts are used; an ester is preferably the Amino acid used.

The difference in the solubility of the diastereomers produced in each case Salt allows the selective crystallization of one form and regeneration the respective optically active compounds from the mixture.

You can also a free carboxylic acid I by esterification into a convert easily cleavable carboxylic acid ester.

For example, the tert-butyl esters are obtained by reacting the acids with isobutylene.

Conversely, the acid I can be obtained in freedom from an ester obtained can be set, e.g. by solvolysis, in particular by acid hydrolysis. The at The tert-butyl esters obtained particularly advantageously in the synthesis are, for example, with trifluoroacetic acid cleaved at temperatures between 0 and 400.

The new cephem derivatives are solid crystalline or amorphous products1 They form solid, often crystalline, alkali metal, ammonium and alkaline earth metal salts as Salts with organic bases such as diethylamine, triethylamine, Diethanolamine, N-ethyl-diethanolamine, pyrrolidine, piperidine, N-ethylpiperidine, 1- (2-hydroxyethyl) piperidine, Morpholine, procaine, benzylamine, dibenzylamine, 1-phenyl-2-propylamine and others Amines, such as those commonly used for the production of cephalosporin salts Find.

Of the alkali metal salts, the sodium and the Potassium salts matter. They can be made by getting a solution an acid I in an organic solvent with a solution of sodium or Potassium salt of a fatty acid, e.g. diethyl acetic acid or 2-ethylcaproic acid, in a solvent, e.g. acetone or n-butanol, or a solvent mixture offset. The salts precipitating in the process or on addition of ether can be filtered off will.

Basic compounds of the formula I can be mixed with acids in the usual way Manner can be converted into the associated acid addition salts, e.g. into the hydrochloride or citrate.

Since the compounds I have no sharp melting points, will appropriately characterized by other physical indicators, especially advantageous due to their nuclear magnetic resonance spectra. You can also use the thin layer chromatogram be characterized. For this purpose, Merck TLC precast silica gel plates can be used F254 can be used (superplasticizer, e.g. dioxane / water 85:15).

The new compounds can be mixed with solid, liquid and / or semi-liquid pharmaceutical carriers as pharmaceuticals in human or veterinary medicine use be det. The carrier substances used are organic or inorganic substances suitable for enteral, preferably oral, e.g. but are also suitable for parenteral or topical application and those with do not react to the new compounds, such as water, vegetable oils, benzyl alcohols, Polyethylene glycols, gelatine, lactose, starch, magnesium stearate, talc, petroleum jelly, Cholesterol. For enteral use, e.g. tablets, capsules, coated tablets, Syrups, juices, granules (dry juices) or suppositories. For parenteral application In particular, solutions, preferably oily or aqueous solutions, are used as well Suspensions, emulsions or implants, for topical application ointments, creams, Lotions, pastes or powders. These preparations can be sterilized or with auxiliaries, Emulsifiers, salts to influence the osmotic pressure, buffer substances, Dyes are added. They can also contain other active ingredients.

The compounds of general formula I and their easily cleavable Esters and their physiologically acceptable salts can essentially be used in the same way as the well-known compound cephalexin used to fight infections be used; they are preferably used in dosages between 1 and 5000 in particular administered between 200 and 2000 mg per dosage unit. The daily dosage is preferably between 4 and 100, in particular between 10 and 60 mg per kg Body weight.

Each of the compounds of the formula mentioned in the following examples I is particularly suitable for the production of pharmaceutical preparations.

The IR spectra were measured in KBr.

The NMR spectra are recorded in dimethyl sulfoxide.

DMF = dimethylformamide, 7-ACS = 7-aminocephalosporanic acid, DCC = dicyclohexylcarbodiimide, THF = tetrahydrofuran, BOC = tert-butyloxycarbonyl, MCC = -3-methyl-3-cephem-4-carboxylic acid.

Unless otherwise stated, the following examples the substituted 2-phenylglycines of the formula II (or their derivatives) as racemates used; accordingly, the compounds of the formula I are then used as mixtures two epimers obtained.

Example 1 9.26 g of 7--2-BOC-amido-2- (3-hydroxyphenyl) -acetamido7- 3-methyl-3-cephem-4-carboxylic acid (prepared according to C.W. Ryan et al. J. Med. Chem. 12, 310 (1969)) in 200 ml of dichloromethane and 11.2 ml of triethylamine, gives at 0-5 ° C. 3.68 g of propionyl chloride, dissolved in 30 ml of dichloromethane, are added while stirring with cooling for a further 30 minutes, the solvent is distilled off and suspended the residue in 150 ml of THF, the mixture is stirred into a solution of 60 g of sodium hydrogen carbonate in 600 ml of water, stirred for 20 minutes, most of the THF distilled off and extract the aqueous solution (pH about 9) with a little ethyl acetate. The extract is separated; and the aqueous phase brought to pH 3 with hydrochloric acid, extracted with ethyl acetate, the extract is dried over sodium sulfate and the solvent is distilled off. Of the The residue is taken up in ether and precipitated with petroleum ether is obtained 7-LD-2-BOC-amido-2- (3-propionyloxyphenyl) -acetamido7-3-methyl-3-cephem-4-carboxylic acid as an amorphous substance; Rf = 0.54 (silica gel / dioxane: water = 85:15), IR: 1775 (Shoulder), 1760, 1718 and 1685 cm1.

By reacting 7--2-BOC-amido-2- (3-hydroxyphenyl) -acetamido7-3-methyl-3-cephem- 4-carboxylic acid available with the acid chlorides of the corresponding carboxylic acids V: 7-LD-2-BOC-amido-2- (3-acetoxyphenyl) -acetamido7-MCC, 7-LD-2-BOC-amido-2- (3-butyryloxyphenyl) -acetamido7-MCC, 7-LD-2-BOC-amido-2- (3-pentanoyloxyphenyl) -acetamido7-MCC, 7w-2-BOC-amido-2- (3-hexanoyloxyphenyl) -acetamido7-MCC, 7-LD-2-BOC-amido-2- (3-octanoyloxyphenyI) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-decanoyloxyphenyl) -acetamido] -MCC, 7- / D-2-BOC-amido-2- (3-pivaloyloxyphenyl) -acetamido7-MCC, 7-cD-2-BOC-amido-2-g3- (2-methylpropionyloxy) -phenyl7-acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-methylbutyryloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- / 3- (5-methylhexanoyloxy) -phenyl7-acetamido3-MCC 7-ED-2-BOC-amido-2- / 3- (3-fluoropropionyloxy) - phenyl7-acetamidoj-MCC 7-ED-2-BOC-amido-2- / 3- (3-chloropropionyloxy) -phenyl7-acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-chloropentanoyloxy) -phenyl ] acetamido -MCC 7-CD-2-BOC-amido-2-L3- (3-chlorobutyryloxy) -phenyl7-acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-chloropentanoyloxy) - phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-chlorohexanoyloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-chlorobutyryloxy) -phenyl] -acetamido-MCC 7- {D-2-BOC-amido-2- [3- (6-chlorohexanoyloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-methoxyacetoxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-ethoxyacetoxy) phenyl] acetamidoj-MCC 7-ED-2-BOC-amido-2- / 3- (2-tert-butyloxyacetoxy ) -phenyl7-acetamido3 -MCC 7-ED-2-BoC-amido-2-L3- (3-methoxypropionyloxy) -pheny17-acetamido} -MCC 7-tD-2-BOC-amido-2- / 3- (3-ethoxypropionyloxy) -phenyl7 -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-methoxybutyryloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-ethoxybutyryloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-methoxyhexanoyloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-ethoxyhexanoyloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-methoxybutyryloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-ethoxybutyryloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-butyloxybutyryloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-acetoxyacetoxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-acetoxypropionyloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-acetoxybutyryloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-acetoxyhexanoyloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-acetoxybutyryloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-butyryloxybutyryloxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (6-acetoxyhexanoyloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-methoxycarbonylacetoxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-ethoxycarbonylacetoxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (3-ethoxycarbonylpropionionyloxy) phenyl] acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (4-ethoxycarbonylbutyryloxy) -phenyl7- acetamidoj -MCC 7-ED-2-BOC-amido-2- / 3- (5-ethoxycarbonylpentanoylOxy) -phenyl7- acetamidoi-MCC 7- {D-2-BOC-amido-2-13- (2,2-dichloroacetoxy) -phenyl7-acetamido? -MCC 7- {D-2-BOC-amido-2- [3- (2.2, 2-trichloroacetoxy) phenyl] acetamidoi MCC 7- {D-2-BOC-amido-2- [3- (2,3-dichloropropionyloxy) -phenyl] -acetamido3 -MCC 7-fD-2eBOC-amido-2- / 3- (2,3-dichlorobutyryloxy) -phenyl7-acetamido} -MCC 7- {D-2-BOC-amido-2-l3- (3,4-dichlorobutyryloxy) -phenyl7-acetamido} -MCC 7- {D-2-BOC-amido-2- [3- (2-hydroxycarbonylacetoxy) -phenyl] -acetamido} -MCC 7- {D-2-BOC-amido-2- / 3- (3-hydroxycarbonylpropionyloxy) -phenyl7-acetamido3 -MCC 7- {D-2-BOC-amido-2- [3- (4-hydroxycarbonylbutyryloxy) phenyl7 -acetamido3-MCC 7- {D-2-BOC-amido-2- / 3- (5-hydroxycarbonylpentanoyl-oxy) -phenyl acetamido 3-MCC example 2 A solution of 2.2 g of 7-S5-2-BOC-amido-2- (3-propionyloxyphenyl) -acetamidol7- 3-methyl-3-cephem-4-carboxylic acid in 300 ml of trifluoroacetic acid for 10 minutes at room temperature stand, the trifluoroacetic acid is distilled off, and diethyl ether is added to the residue and receives the trifluoroacetate of 7-LD-2-amino-2- (3-propionyloxyphenyl) acetamido] -3-methyl-3-cephem-4-carboxylic acid as Fessubstanz; IR: 1770 (shoulder), 1758, 1700 (shoulder) and 1670 cm 1.

Example 3 2.0 g of the trifluoroacetate of 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] -3-methyl-3-cephem-4-carboxylic acid are dissolved in a little water, brought to pH 4-5 with 4N NaOH, left to stand at 00 for 24 hours and, after filtration, receives 7-D-2-amino-2- (3-propionyloxyphenyl) acetamido] -3-methyl-3-cephem-4-carboxylic acid; Rf = 0.39 (silica gel / dioxane: water = 85:15).

The compounds of the formula I mentioned in Examples 4 to 53 below can be obtained analogously to Examples 2 and 3 from the other starting materials mentioned in Example 1 by reaction with trifluoroacetic acid and NaOH: Example | Compound of formula I. 4. 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido] -MCC 5. 7- [D-2-amino-2- (3-butyryloxyphenyl) acetamido] -MCC 6. 7-g5-2-amino-2- (3-pentanoyloxyphenyl) -acetamido7-MCC 7. 7-ffi-2-amino-2- (3-hexanoyloxyphenyl) -acetamido7-MCC 8. 7-Li5-2-amino-2- (3-oxtanoyloxyphenyl) -acetamido7-MCC 9. 7-LD-2-amino-2- (3-decanoyloxyphenyl) acetamido7-MCC 10. 7-LD-2-amino-2- (3-pivaloyloxyphenyl) -acetamido7-MCC 11. 7- {D-2-amino-2- [3- (2-methylpropionyloxy) phenyl] acetamido-MCC 12. 7- {D-2-amino-2- [3- (2-methylbutyryloxy) phenyl] acetamidoj-MCC 13. 7-tD-2-amino-2- / 3- (5-methylhexanoyloxy) -phenyl7- acetamido§-MCC 14. 7- {D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] - acetamidoj-MCC 15. 7- {D-2-amino-2- [3- (3-chloropropinyloxy) phenyl] - acetamido} -MCC 16. 7-CD-2-amino-2-L3- (3-bromopropionyloxy) -phenyl7- acetamido} -MCC 17. 7- {D-2-amino-2- [3- (3-chloropentanoyloxy) phenyl] - acetamido3-MCC 18. 7- {D-2-amino-2- [3- (3-chlorohexanoyloxy) phenyl] - acetamido} -MCC 19. 7- {D-2-amino-2- [3- (4-chlorobutyryloxy) phenyl] - acetamido} -MCC 20. 7- {D-2-amino-2- [3- (6-chlorohexanoyloxy) phenyl] - acetamido} -MCC 21. 7- {D-2-amino-2- [3- (2-methoxyacetoxy) phenyl] - acetamido3 -MCC 22. 7- {D-2-amino-2- [3- (2-ethoxyacetoxy) phenyl] - acetamido} -MCC 23. 7-CD-2-amino-2- / 9- (2-tert-butyloxyacetoxy) -phenyl7- acetamido} -MCC 23 a. 7-j D-2-aminoi-2- [3- (3-chlorobutyryloxy) phenyl] - acetamido3 -MCC Example compound of formula I. 24. 7- {D-2-amino-2- [3- (3-methoxypropionyloxy) phenyl] - acetamidoj-MCC 25. 7- {D-2-amino-2- [3- (3-ethoxypropionyloxy) phenyl] - acetamidot MCC 26. 7- {D-2-amino-2- [3- (3-methoxybutyryloxy) phenyl] - acetamido} -MCC 27. 7- {D-2-amino-2- [3- (3-ethoxybutyryloxy) phenyl] - acetamido} -MCC 28. 7-CD-2-amino-2- / 9- (3-methoxyhexanoyloxy) phenyl7- acetamido3 -MCC 29. 7- {D-2-amino-2- [3- (3-ethoxyhexanoyloxy) phenyl] - acetamido-MCC 30. 7-tD-2-amino-2-L3- (4-methoxybutyryloxy! -Pheny7- acetamido} -MCC 31. 7- {D-2-amino-2- [3- (4-ethoxybutylryloxy) phenyl] - acetamidoj -MCC 32.7-CD-2-Amino-2-L3- (4-butyloxybutyryloxy) phenyl7- acetamidoj -MCC 33. 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamido} -MCC 45. 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamido} -MCC 35. 7- {D-2-amino-2- [3- (3-acetoxybutyryloxy) phenyl] - acetamido} -MCC 36. 7- {D-2-amino-2- [3- (3-acetoxyhexanoyloxy) phenyl] - acetamido-MCC 37. 7- [D-2-amino-2- [3- (4-acetoxybutyryloxy) phenyl] - acetamidoj -MCC 38. 7-eD-2-amino-2-13- (4-butyryloxybutyryloxy) -phenyl7- acetamido} -MCC 39. 7- {D-2-amino-2- [3- (6-acetoxyhexanoyloxy) phenyl] - acetamido} -MCC 40. 7- {D-2-amino-2- [3- (2-methoxycarbonylacetoxy) phenyl] - acetamido} -MCC 41. 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamido3-MCC Example 1 Compound of Formula I. 42. 7- {D-2-amino-2- [3- (3-ethoxycarbonylpropionyloxy) - phenyl] acetamido} -MCC 43. 7- {D-2-amino-2- [3- (4-ethoxycarbonylbutyryloxy) - phenyl7-acetamidoj-MCC 44. 7- {D-2-amino-2- [3- (5-ethoxycarbonylpentanoyloxy) - phenyl7-acetamidot-MCC 45. 7- {D-2-amino-2- [3- (2,2-dichloroacetoxy) phenyl] - acetamido-MCC 46. 7- {D-2-amino-2- [3- (2,2,2-trichloroacetoxy) phenyl] - acetamido 47. 7- {I) -2-amino-2- / 3- (2,3-dichloropropionyloxy) -phenyl7- acetamido} -MCC 48. 7- {D-2-amino-2- [3- (2,3-dichlorobutyryloxy) phenyl] - acetamidoj-MCC 49. 7- {D-2-amino-2- [3- (3,4-dichlorobutyryloxy) phenyl] - acetamido} -MCC 50.71D-2-Amino-2-Z3- (2-hydroxycarbonylacetoxy) -phenyl7- acetamido} -MCC 51. 7- {D-2-amino-2- [3- (3-hydroxycarbonylpropionyloxy) - phenyl7-acetamido} -MCC 52. 7- {D-2-amino-2- [3- (4-hydroxycarbonylbutyryloxy) - phenyl7-acetamido -MCC 53. 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) - phenyl7-acetamidoi -MCC Example 54 A solution of 4.33 g of the triethylammonium salt of 7-LZ-D- (2-ethoxycarbonyl-methylvinyl) -amino-2- (3-hydroxyphenyl) -acetamido7-MCC (can be prepared by heating equimolar amounts) is added dropwise of 7- [2-D-amino-2- (3-hydroxyphenyl) acetamido] -MCC and ethyl 2-acetylacetate in dichloromethane in the presence of triethylamine) and 2.1 ml of triethylamine in 50 ml of dichloromethane with ice-cooling 1 45 ml of ethyl chlorocarbonate dissolved in 5 ml of dichloromethane, stirred for a further 30 minutes while cooling with ice, the solvent is distilled off, the residue is taken up in 50 ml of THF, stirred with 100 ml of 0.2N NaHCO3 solution, extracted with diethyl ether, brings the aqueous phase with HCl to pH = 3, extracted with ethyl acetate and precipitates the 7- / 2-D-amino-2- (3-ethoxycarbonyloxyphenyl) -acetamido7-MCC with petroleum ether.

Example 55 4.63 g of 7-lU-D-BOC-amido-2- (3-hydroxyphenyl) acetamido7-MCC are added dropwise and 5.6 ml of triethylamine, dissolved in 15 ml of dichloromethane with ice cooling, 0.95 g of methyl chloroformate, dissolved in 3 ml of dichloromethane, stirred for a further 20 minutes at 00, the solvent is distilled from, the residue is taken up in 100 ml of THF, the solution is stirred for 30 minutes with 30 g Sodium hydrogen carbonate, dissolved in 300 ml of water, distilled 150 ml of the solvent from, the remaining mixture extracted with ethyl acetate, brings with hydrochloric acid the aqueous phase to pH = 3, extracted with ethyl acetate, the organic dried Phase over sodium sulfate, the solvent is distilled off and obtained after taking up in diethyl ether and reprecipitation with petroleum ether 7-g-D-BOC-amido-2- (3-methcxycarbonyloxyphenyl) -acetamido7-MCC.

By reacting 7- / b-2-BOC-amido-2- (3-hydroxyphenyl) -acetamido7-MCC available with the corresponding chloroformic acid esters RO-COCl: 7- [D-2-BOC-amido-2- (3-propyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-butyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-pentyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-hexyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-octyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-decyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- [D-2-BOC-amido-2- (3-isopropyloxycarbonyloxyphenyl) -acetamido7-MCC, 7-LD-2-BOC-amido-2- (3-isobutyloxycarbonyloxyphenyl) -acetamido7-MCC, 7-Lri-2-BOC-amido-2- (3-sec-butyloxycarbonyloxyphenyl) -acetamido7-MCC, 7-LD-2-BOC-amido-2- (3-tert-butyloxycarbonyloxyphenyl) -acetamido7-MCC, 7- {D-2-BOC-amido-2- [3- (1-methylbutyloxycarbonyloxy) phenyl] - acetamido} -MCC, 7- [D-2-BOC-amido-2- / 3- (1-methylpentyloxycarbonyloxy) -phenyl7-acetamido3-MCC, 7- {D-2-BOC-amido-2- [3- (1-methylheptyloxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2-g- (3-methylbutyloxycarbonyloxy) -phenyl-7-acetamidoj -MCC, 7- {D-2-BOC-amido-2- / 3- (4-methylpentyloxycarbonyloxy) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-fluoroethoxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-chloroethoxycarbonyloxy ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (3-bromoethoxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-methoxyethoxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-ethoxyethoxycarbonyloxy ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (3-methoxypropyloxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (3-ethoxypropyloxycarbonyloxy ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (4-methoxybutyloxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (4-ethoxybutyloxycarbonyloxy) ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (4-butyloxybutyloxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- (3-carbethoxymethoxycarbonyloxyphenyl) acetamido ] -MCC, 7- {D-2-BOC-amido-2- [3- (1-carbethoxyethoxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-carbethoxyethoxycarbonyloxy ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-acetoxyethoxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (2-acetoxypropyloxycarbonyloxy ) -phenyl] -acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (3-acetoxypropyloxycarbonyloxy) phenyl] acetamido} -MCC, 7- {D-2-BOC-amido-2- [3- (4-acetoxybutyloxycarbonyloxy ) -phenyl] -acetamido} -MCC.

Example 56 Analogously to Example 2, 7- [2-D-BOC-amido-2- (3-methoxycarbonyloxyphenyl) -acetamidol-MCC by treating with trifluoroacetic acid the trifluoroacetate of the 7-B2-amino-2- (3-methoxycarbonyloxyphenyl) -acetamido] -MCC obtainable and therefrom analogously to Example 3 by reacting with dilute NaOH the free 7- [2-Amino-2- (3-methoxycarbonyloxyphenyl) acetamido MCC.

Analogously, from the other BOC derivatives mentioned in Example 55, as starting materials qie compounds of the formula 1 mentioned in Examples 57 to 88 below can be obtained: Example compound of formula I. 57 7- [D-2-amino-2- (3-propyloxycarbonyloxyphenyl) - acetamido] -MCC 58 7- [D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido] -MCC 59 7- [D-2-amino-2- (3-pentyloxycarbonyloxyphenyl) - acetamido] -MCC 60 7- [D-2-amino-2- (3-hexyloxycarbonyloxyphenyl) - acetamido] -MCC 61 7- [D-2-amino-2- (3-oxtyloxycarbonyloxyphenyl) - acetamido] -MCC 62 7- [D-2-amino-2- (3-decyloxycarbonyloxyphenyl) - acetamido] -MCC 63 7- [D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) - acetamido] -MCC 64 7- [D-2-amino-2- (3-isobutyloxycarbonyloxyphenyl) - acetamido] -MCC 65 7- [D-2-amino-2- (3-sec-butyloxycarbonyloxyphenyl) - acetamido] -MCC 66 7- [D-2-amino-2- (3-tert-butyloxycarbonyloxyphenyl) - acetamido] -MCC Example compound of formula I. 67 7- {D-2-amino-2- [3- (1-methylbutyloxycarbonyloxy) - phenyl] acetamido} -MCC 68 7- {D-2-amino-2- [3- (1-methylpentyloxycarbonyloxy) - phenyl] acetamido} -MCC 69 7- {D-2-amino-2- [3- (1-methylheptyloxycarbonyloxy) - phenyl] acetamido} -MCC 70 7- {D-2-amino-2- [3- (1-methylbutyloxycarbonyloxy) - phenyl] acetamido} -MCC 71 7- {D-2-amino-2- [3- (4-methylpentyloxycarbonyloxy) - phenyl] acetamido} -MCC 72 7- {D-2-amino-2- [3- (2-fluoroethoxycarbonyloxy) - phenyl] acetamido} -MCC 73 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] acetamido} -MCC 74 7- {D-2-amino-2- [3- (2-bromoethoxycarbonyloxy) - phenyl] acetamido} -MCC 75 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxy) - phenyl] acetamido} -MCC 76 7- {D-2-amino-2- [3- (2-ethoxyethoxycarbonyloxy) - phenyl] acetamido} -MCC 77 7- {D-2-amino-2- [3- (3-methoxypropyloxycarbonyloxy) - phenyl] acetamido} -MCC 78 7- {D-2-amino-2- [3- (3-ethoxypropyloxycarbonyloxy) - phenyl] acetamido} -MCC 79 7- {D-2-amino-2- [3- (4-methoxybutyloxycarbonyloxy) - phenyl] acetamido} -MCC 80 7- {D-2-amino-2- [3- (4-ethoxybutyloxycarbonyloxy) - phenyl] acetamido} -MCC 81 7- {D-2-amino-2- [3- (4-butyloxybutyloxycarbonyloxy) - phenyl] acetamido} -MCC 82 7- {D-2-amino-2- (3-carbethoxymethoxycarbonyloxy- phenyl) acetamido] -MCC 83 7- {D-2-amino-2- [3- (1-carbethoxyethoxycarbonyl- oxy) phenyl] acetamido} -MCC 84 7- {D-2-amino-2- [3- (2-carbethoxyethoxycarbonyloxy) - phenyl] acetamido} -MCC Example compound of formula I. 85 7- {D-2-Aminoi-2- [3- (2-acetoxyethoxycarbonyloxy) - phenyg-acetamide -MCC 86 7- {D-2-amino-2- [3- (2-acetoxypropyloxycarbonyloxy) - phenyl] acetamido} -MCC 87 7- {D-2-amino-2- [3- (3-acetoxypropyloxycarbonyloxy) - phenyl) -acetamidoj -MCC 88 7- {D-2-amino-2- [3- (4-acetoxybutyloxycarbonyloxy) - phenyl) acetamido -MCC Example 89 9.26 g of 7- [D-2-BOC-amido-2- (3-hydroxyphenyl) acetamido] -MCC are dissolved in 300 ml of dichloromethane. After adding 13.8 potassium carbonate, 4 g of adipic acid monomethyl ester monochloride, dissolved in a little dichloromethane, are added dropwise at 0-5 ° 8 with stirring, the dichloromethane is distilled off after 20 minutes, the residue is taken up in ethyl acetate, extracted with water, and the aqueous solution is added Phase with hydrochloric acid to pH = 3, extracted with ethyl acetate, the organic phase is dried over sodium sulfate, the solvent is distilled off and the 7- {D-2-BOC-amido-2- [3- (5-methoxycarbonylpentanoyloxy) - phenyl] acetamido} -MCC; Rf = 0.58 (silica gel / dioxane: water = 85:15).

Analogously to Example 2, the BOC group is obtained by splitting off with trifluoroacetic acid the trifluoroacetate of 7- {D-2-Aminoi-2-D3- (5-methoxycarbonylpentanoyloxy) -phenyl-acetamido} -MCC, IR: 1778 (shoulder), 1760, 1733, 1690 cm 1 (wide).

Analogously to Example 3, the trifluoroacetate is obtained by reaction with NaOH the free 7- {D-2-amino-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl] acetamido} -MCC, Rf = 0.37 (silica gel / dioxane: water = 85:15).

Example 90 To 2.05 g of 2-D-BOC-amido-2- [3- (5-methoxycarbonylpentanoyl) phenyl) acetic acid are added and 0.69 ml of triethylamine in 20 ml of THF at -10 OC 0.65 ml of isobutyl chlorocarbonate, drops to the solution of the mixed carbonic anhydride thus prepared in situ 1.58 g of the triethylammonium salt of 7-amino-MCC, dissolved in 18 ml of 50% aqueous THF, the mixture is stirred for 1 hour at 5 oC and 1 hour at room temperature, distilled remove the THF, add 30 ml of water to the residue, extract with 10 ml of ethyl acetate, bring the aqueous phase with HCl to pH = 3, filtered and the filtrate extracted twice with 25 ml of ethyl acetate each. The organic phase is washed with water over sodium sulfate dried and the solvent was distilled off. After treating the oily residue with diethyl ether / petroleum ether you get 7-fD-2-BOC amido-2-g3- (5-methoxycarbonylpentanoyl) -phenyl2-acetamido} -MCC, from it directly analogous to Example 2, the trifluoroacetate of 7-o) -2-Ainino-2- £ 3- (5-methoxycarbonylpentanoyl) -phenyl) acetamido} -MCC and from this analogous to the example 3 the free 7-tD-2-amino-2-t3- (5-methoxycarbonylpentanoyl) -phenylacetamido, -MCC, Rf = 0.37 (silica gel / dioxane: water = 85:15).

Example 91 The D-2-BOC-amido-2-- used as starting material in Example 90 (5-methoxycarbonylpentanoyl) phenyl) acetic acid is obtained as follows: One adds a mixture of 5.34 g of D-2-BOC-amido-2- (3-hydroxyphenyl) acetic acid and 8.28 g Potassium carbonate in 60 ml dichloromethane at 0 - 5 ° C with stirring 4 g adipic acid monomethyl ester monochloride, dissolved in a little dichloromethane, the solvent is distilled off after 20 minutes, dissolve the residue in ethyl acetate, extract with water, bring the aqueous phase with HC1 to pH = 3 and extracted with ethyl acetate.

After drying over sodium sulfate, the solvent is distilled off and D-2-BOC-amido-2- (3-acetoxypheny) acetic acid, carbonylpentanoyl) phenyl) acetic acid is obtained, -. Rf = 0.66 (silica gel / dioxane: water = 85:15).

The other compounds of the formula VI are also analogous by reaction of D-2-BOC-amido-2- (3-hydroxyphenyl) -acetic acid with the acid chlorides of the acids V available, for example: D-2-BOC-amido-2- (3-acetoxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-butyryloxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-pentanoyloxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-hexanoyloxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-octanoyloxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-decanoyloxyphenyl) -acetic acid, D-2-BOC-amido-2- (3-pivaloyloxyphenyl) -acetic acid, D-2-BOC-amido-2-g3- (2-methylpropionyloxy) -phenyl | -acetic acid, D-2-BOC-amido-2-3 (2-methylbutyloxy) -phenyl) -acetic acid, D-2-BOC-amido-2- [3- (5-methylhexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-fluoropropionyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2-g3- (3-chloropropionyloxy) -phenyl2-acetic acid, D-2-BOC-amido-2- [3- (3-bromopropionyloxy) -phenyl] -acetic acid, D-2-Boc-amido-2-g3- (3-chlorobutyryloxy) -phenylI-acetic acid D-2-BOC-amido-2- [3- (3-chloropentanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-chlorohexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2-g3- (4-chlorobutyryloxy) -phenyl, / - acetic acid, D-2-BOC-amido-2- g3- (6-chlorhexanoyloxy) -phenyl, / - acetic acid, D-2-BOC-amido-2- g3- (2-methoxyacetoxy) -phenyl2-acetic acid, D-2-BOCWamido-2-g3- (2-ethoxyacetoxy) -phenyl,> - acetic acid, D-2-BOC-amido-2- [3- (2-tert-butoxyacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-methoxypropionyloxy) -phenyl] -acetic acid , D-2-BOC-amido-2-g3- (3-ethoxypropionyloxy) -phenyl, / - acetic acid, D-2-BOC-amido-2- [3- (3-methoxybutyryloxy) phenyl] acetic acid, D-2-BOC-amido-2- [3- (3-ethoxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-methoxyhexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-ethoxyhexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-methoxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-ethoxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-butyloxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2-acetoxyacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-acetoxypropionyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-acetoxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-acetoxyhexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-acetoxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-butyryloxybutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (6-acetoxyhexanoyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2-methoxycarbonylacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2-ethoxycarbonylacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-ethoxycarbonylpropionyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-ethoxycarbonylbutyryloxy) phenyl] acetic acid, D-2-BOC-amido-2- [3- (5-ethoxycarbonylpentanoyloxy) phenyl] acetic acid, D-2-BOC-amido-2- [3- (2,2-dichloroacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2,2,2-trichloroacetoxy) -phenyl ]-acetic acid, D-2-BOC-amido-2- [3- (2,3-dichloropropionyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2,3-ldichlorobutyryloxy) -phenyl] - acetic acid, D-2-BOC-amido-2- [3- (3,4-dichlorobutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (2-hydroxycarbonylacetoxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (3-hydroxycarbonylpropionyloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (4-hydroxycarbonylbutyryloxy) -phenyl] -acetic acid, D-2-BOC-amido-2- [3- (5-hydroxycarbonylpentanoyloxy) phenyl] acetic acid, example 92 2.14 g of 7-amino-MCC are suspended in dry acetonitrile, and 1 g of triethylamine is added and 2 ml of N, N-dimethylaniline, cool to 5 ° and drop 12.7 g of trimethylchlorosilane to. After 10 minutes, 2.8 g of D-2-amino-2- are added at 5 ° over the course of 15 minutes. (3-propionyloxyphenyl) acetyl chloride hydrochloride (available from a suspension of D-2-amino-2- (3-propionyloxyphenyl) acetic acid in dry dioxane by sequential Introducing dry phosgene and dry HCl gas), stir for 1 hour at 12 °, add 40 ml of water and then Na2C03 with stirring until a pH = 2.5 is reached is, separates the organic phase, brings the pH of the aqueous phase with it HC1 to a pH value of 2, washes with diethyl ether, brings with dilute aqueous NaOH adjusts the pH to 4, the solvent is distilled until it becomes cloudy Stand overnight at 5 °, filter and dry the precipitate. 7-6D-2-amino-2- (3-propionyloxyphenyl) -acetamido2-MCC is obtained, Rf = 0.39 (silica gel / dioxane: water = 85:15).

Example 93 4.05 g of 7-D-2-amino-2- (3-acryloyloxyphenyl) -acetamidoJ-MCC are passed into a stirred suspension (available from 7-zD-2-BOC-amido-2- (3-hydroxyphenyl) -acetamido7-MCC and acrylic chloride corresponding to the reaction sequence described in Examples 1 to 3) in one Mixture of 60 ml of dioxane and 40 ml of chloroform at 0 ° chlorine up to an increase in weight of 0.75 g, stirred for a further 1 hour, the solvent was distilled off and obtained after chromatographic purification of the residue (silica gel / dioxane: water = 85:15) 7- {D-2-amino-2-g3- (2,3-dichloropropionyloxy) -phenylI-acetamidol, MCC.

Example 94 A stirred suspension of 4.8 g of 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) phenyl] acetamidoi-MCC is added dropwise (available from 7-gD-2-BOC-amido-2- (3-hydroxyphenyl) -acetamido2-MCC and adipic acid mono-tert-butyl ester monochloride corresponding to the reaction sequence described in Examples 1 to 3) in 70 ml Dioxane, ethereal diazomethane solution until a pale yellow color persists, adds 3 drops of acetic acid, distilled off the solvent and obtained as residue 7-iD-2-amino-2- / 3 (5-methoxycarbonylpentanoyloxy) phenyl) acetamido MCC methyl ester.

Example 95 493 mg of 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) -phenyl-acetamido7-MCC are dissolved and 53 mg of Na2CO3 in 8 ml of water, stirred for 30 minutes and obtained after freeze-drying of the solution the sodium salt of 7- {D-2-amino-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl) acetamidol MCC.

Example 96 a) 10.5 g of 7- £ D-2-BOC-amido-2- (3-hydroxyphenyl) acetamido / cephalosporanic acid are dissolved (obtainable by the method of C.W. Ryan et al. J. Med. Chem. 12, 310 (1969) under Use of 7-ACS instead of 3-deacetoxy-7-ACS) in 300 ml of dichloromethane 13.8 g of potassium carbonate are added dropwise at 0-5 ° while stirring, 4 g of adipic acid monomethyl ester chloride, dissolved in a little dichloromethane, the dichloromethane is distilled off after 20 minutes, takes up the residue in ethyl acetate, extracted with water, brings the aqueous Phase with Hydrochloric acid to pH = 3, extracted with ethyl acetate, dried the organic phase over sodium sulfate, the solvent is distilled off and obtained the residue is 7- {D-2-BOC-amido-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl] acetamido] cephalosporanic acid.

By reacting 7-gD-2-BOC-amido-2- (3-hydroxyphenyl) -acetamido, 7-cephalosporanic acid are analogous obtainable with the acid chlorides of the corresponding carboxylic acids V: 7- [D-2-BOC-amido-2- (3-acetoxyphenyl) -acetamido] -cephalosporanic acid, 7- (D-2-BOC-amido-2- (3-propionyloxyphenyl) -acetamidoj cephalosporanic acid, 7-vD-2-BOC-amido-2- (3-butyryloxyphenyl) -acetamidoJ-cephalosporanic acid, 7-eD-2-BOC-amido-2- (3-pentanoyloxyphenyl) -acetamidoStcephalosporanic acid 7-gD-2-BOC-amido-2- (3-hexanoyloxyphenyl) -acetamido, / - cephalosporanic acid, 7-t) -2-BOC-amido-2- (3-decanoyloxyphenyl) -acetamidoJ-cephalosporanic acid, 7- [D-2-BOC-amido-2- (3-pivaloyloxyphenyl) -acetamido] cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (3-fluoropropionyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (3-chloropropionyloxy) phenyl] acetamidoj-cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (3-bromopropionyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (3-chlorobutyryloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-ethoxyacetoxy) phenyl] acetamido} cephalosporanic acid, 7-D-2-BOC-aido-2-C3- (3-methoxypropiony acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (4-ethoxybutyryloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (4-butyloxybutyryloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-acetoxyacetoxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (3-acetoxypropionyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- g3- (4-acetoxybutyryloxy) -phenyl2-acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (6-acetoxyhexanoyloxy) -phenyl] -acetamido3-cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-methoxycarbonylacetoxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-ethoxycarbonylacetoxy) -phenyl] -acetamido-3-cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (5-ethoxycarbonylpentanoyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (5-hyroxycarbonylpentanoyloxy) -phenyl] -acetamido) -cephalosporanic acid, b) Analogously to the reaction sequence given in Examples 2 and 3, one obtains from 7- {D-2-BOC-amido-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl) acetamido-cephalosporanic acid by reaction with trifluoroacetic acid and then with NaOH the free 7- {D-2-BOC-amido-2- [3- (5-methoxycarbonylpentanoyloxy) -phenyl] -acetamido] -cephalosporanic acid.

The compounds of the formula I mentioned in Examples 97 to 119 below can be obtained analogously from the BOC derivatives mentioned in Example 96a: Example compound of the formula I 4 1 # 97 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido} - cephalosporanic acid, 98 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] - cephalosporanic acid, 99 7- [D-2-amino-2- (3-butyryloxyphenyl) acetamido] - cephalosporanic acid, 100 7- [D-2-amino-2- (3-pentanoyloxyphenyl) acetamido] - cephalosporanic acid, 101 7- [D-2-amino-2- (3-hexanoyloxyphenyl) acetamido] - cephalosporanic acid, 102 7- [D-2-amino-2- (3-decanoyloxyphenyl) acetamido] - cephalosporanic acid, 103 7- [D-2-amino-2- (3-pivaloyloxyphenyl) acetamido] - cephalosporanic acid, 104 7- {D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] - acetamidoJ-cephalosporanic acid, 105 7- {D-2-amino-2- [3- (3-chloropropionyloxy) phenyl] - acetamido3 -cephalosporanic acid, 106 7- {D-2-amino-2- [3- (3-bromopropionyloxy) phenyl] - acetamido-cephalosporanic acid 107 7- {D-2-amino-2- [3- (3-chlorobutyryloxy) phenyl] - acetamido-cephalosporanic acid, 108 7- {D-2-amino-2- [3- (2-ethoxyacetoxy) phenyl] - acetamido3-cephalosporanic acid, 109 7- {D-2-amino-2- [3- (3-methoxypropionyloxy) phenyl] - acetamido-cephalosporanic acid, 110 7-2-Amino-2- £ 3- (4-ethoxybutyryloxy) phenyl2 acetamido3-cephalosporanic acid, 111 7- {D-2-amino-2- [3- (4-butyloxybutyryloxy) phenyl] - acetamido3 -cephalosporanic acid, 112 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamidoi -cephalosporanic acid> 113 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamido2-cephalosporanic acid, Example compound of formula I. 114 7- {D-2-amino-2- [3- (4-acetoxybutyryloxy) phenyl] - acetamido} -caphalosphoranic acid, 115 7- b-2-amino-2-g3- (6-acetoxyhexanoyloxy) -phenyl2- acetamido) -cephalosporanic acid, 116 7- {D-2-amino-2- [3- (2-methoxycrbonylacetoxy) phenyl] - acetamidof-cephalosporanic acid, 117 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamido3 cephalosporanic acid 118 7- {D-2-amino-2- [3- (5-ethoxycarbonylpenanoyloxy) - phenyl) -acetamidoi-cephalosporanic acid, 119 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) - phenyl) acetamido3-cephalosporanic acid.

Example 120 Analogously to Example 55, 7- [2-D-BOC-amido-2- (3-hydroxyphenyl) acetamido / cephalosporanic acid are obtained in dichloromethane with ice cooling and in the presence of triethylamine by reaction with the corresponding chloroformic acid esters RO-COCl those mentioned below BOC derivatives of the compounds of the formula I obtainable: 7- [2-D-BOD-amido-2- (3-methoxycarbonylphenyl) acetamido] -cephalosporanic acid, 7-b-2-B0C-amido- 2- (3-butyloxycarbonyloxyphenyl) -acetamido) -cephalosporanic acid, 7- (D-2-BOC-amido-2- (3-decyloxycarbonyloxyphenyl) -acetainido? -Cephalosporanic acid, 7- (D-2-BOC-amido-2- (3-isopropyloxycarbonyloxyphenyl) -acetamido) -cephalosporanic acid, 7-fD-2-B0C-amido-2- £ 3- (2-chloroethoxycarbonyloxy) phenyl) -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-bromoethoxycarbonyloxy) -phenyl] -acetamido {-cephalosporanic acid 7- {D-2-BOC-amido-2- [3- (2-methoxyethoxycarbonyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-ethoxyethoxycarbonyloxy) phenyl] acetamidoephalic acid, 7- {D-2-BOC-amido-2- [3- (2-methoxybutyloxycarbonyloxy) phenyl] acetamido} -cephalosporanic acid, 7-fD-2-B0C-amido-2-3 (4-butyloxybutyloxycarbonyloxy) -phenyl) -acetamido3-cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-carbäthoxyäthoxycarbonyloxy) -phenyl] -acetamido-cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-acetoxyethoxycarbonyloxy) -phenyl] -acetamido} -cephalosporanic acid, 7- {D-2-BOC-amido-2- [3- (2-acetoxybutyloxycarbonyloxy) phenyl] acetamido-3-cephalosporanic acid.

Analogous to the reaction sequence described in Examples 2 and 3, the BOC derivatives of the compounds of the formula I mentioned in Example 120 are converted into the free compounds of the formula I mentioned in Examples 121 to 133 below by reacting with trifluoroacetic acid and releasing them from the trifluoroacetate with dilute NaOH available: Example compound of formula 1 121 7- [D-2-amino-2- (3-methoxycarbonyloxyphenyl) - acetamido2-cephalosporanic acid, 122 7- [D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido] -cephalosporanic acid, 123 7- [D-2-amino-2- (3-decyloxycarbonyloxyphenyl) - acetamido? -cephalosporanic acid, 124 7- [D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) - acetamidol-cephalosporanic acid, 125 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 126 7- {D-2-amino-2- [3- (2-bromoethoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 127 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, Example compound of formula I. 128 7- {D-2-amino-2- [3- (2-ethoxyethoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 129 7- {D-2-amino-2- [3- (2-methoxybutyloxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 130 7- {D-2-amino-2- [3- (2-butyloxybutyloxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 131 7- Ü) -2-Amino-2- £ 3- (2-carbäthoxyäthoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 132 7-CD-2-amino-2-0- (2-acetoxyethoxycarbonyloxy) - phenyl] -acetamido} -cephalosporanic acid, 133 7- {D-2-amino-2- [3- (2-acetoxybutyloxycarbonyloxy) - phenyl) acetamido3-cephalosporanic acid.

Example 134 0.93 g of 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido] cephalosporanic acid is suspended and 232 mg of 1-methyltetrazole-5-thiol in 8 ml of water at room temperature, brings the Reactants by adding NaHCO3 in solution, the pH being between 5 and 6 is, heated to 60 for 1 hour, bring the reaction mixture with dilute aqueous NaOH to pH 8, extracted with a little ethyl acetate, bring the aqueous phase with it HCl to pH 3, extracted several times with ethyl acetate, the organic phase is dried over Na2S04, the solvent is distilled off and obtained after chromatographic Purification (silica gel / dioxane: water = 85:15) 7- £ D-2-amino-2- (3-acetoxyphenyl) acetanido) -3- (1-methyl tetrazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid.

Analogously to Example 134, the compounds of the formula I mentioned in Examples 135 to 168 below can be obtained from the cephalosporanic acids mentioned in Examples 97 to 119 and 121 to 133 by reaction with 1-methyltetrazole-5-thiol: Example compound of formula I. 135 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] - 3 (1 -methyl-tetrazolyl- 5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 135a 7- [D-2-amino-2- (3-butyryloxyphenyl) acetamido] - 3- (1-methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 136 7- [D-2-amino-2- (3-pentanoyloxyphenyl) acetamido] - 3- (1-methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 137 7-D-2-amino-2- (3-hexanoyloxyphenyl) -acetamido- 3- (1-methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 138 7- [D-2-amino-2- (3-decanoyloxyphenyl) acetamido] - 3- (1-methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 139 7- [D-2-amino-2- (3-pivaloyloxyphenyl) acetamido] - 3- (1-methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 140 7- {D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] - acetamidoj-3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 141 7- {D-2-amino-2- [3- (3-chloropropionyloxy) phenyl] - acetamido3 -3- (1 -methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 142 7- {D-2-amino-2- [3- (3-bromopropionyloxy) phenyl] - acetamido} -3- (1 -methyl-tetrazoiyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 143 7- {D-2-amino-2- [3- (3-chlorobutyryloxy) phenyl] - acetamido} -3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 144 7- {D-2-amino-2- [3- (3-ethoxyacetoxy) phenyl] - acetamido-3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, Example compound of formula I. 145 7- {D-2-amino-2- [3- (3-methoxypropionyloxy) phenyl] - acetamido} -3-1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 146 | 7 - {D-2-amino-2- [3- (4-ethoxybutyryloxy) phenyl] - acetamido} -3 (1 -methyl-tetrazolyl-S-mercaptomethyl) - 3-cephem-4-carboxylic acid, 147 7- {D-2-amino-2- [3-4-butyloxybutyryloxy) phenyl] - acetamido} -3- (1-methyl-tetrazolyl-5-metcaptomethyl) - 3-cephem-4-carboxylic acid, 148 | 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamido} -3- (1 -methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 149 | 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamidoJ-3- (1 -methyl-tetrazolyl-S-mercaptomethyl) - 3-cephem-4-carboxylic acid, 150 | 7- {D-2-amino-2- [3- (4-acetoxybutyryloxy) phenyl] acetamido} -3- (1 -methyl-tetrazolyl- 5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 151 | 7- {D-2-amino-2- [3- (6-acetoxyhexanoyloxy) phenyl] - acetamido-3- (1 -methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 152 7- {D-2-amino-2- [3- (2-methoxycarbonylacetoxy) phenyl] - acetamido} -3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 153 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamido} -3- (1-methyl-tertrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 154 | 7- {D-2-amino-2- [3- (5-ethoxycarbonylpentanoyloxy) phenyl-acetamido3-3 (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 155 7-D-2-amino-2- £ 3- (5-hydroxycarbonylpentanoyloxy) - phenyl; -acetamidoJ-3- (1 -methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 156 7-D-2-amino-2- (3-methoxycarbonyloxyphenyl) -acetamido) 3 (1 methyl-tetrazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, Example compound of the formula @ 157 7- [D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido? -3- (1-methyl-tetrazolyl-5-mercaptoiRethyl) - 3-cephem-4-carboxylic acid, 158 | 7- [D-2-amino-2- (3-decyloxycarbonyloxyphenyl) - acetamido7-3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 159 7- [D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) acetamido? -3- (1-methyl-tetrazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 160 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] acetamido} -3- (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 161 | 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxy) - phenylJ-acetamido {-3- (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 162 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxycarbonyloxy) - phenyl7-acetamido} -3- (1-methyl-tetrazolyl-5-mercapo- ~ methyl) -3-cephem-4-carboxylic acid, 163 7- {D-2-amino-2- [3- (2-ethoxycarbonyloxy) - phenyl7-acetamido§-3- (1-methyl-tetrazolyl-5-mercapto- - methyl) -3-cephem-4-carboxylic acid, 164 7- {D-2-amino-2- [3- (4-methoxybutyloxycarbonyloxy) - phenyl] acetamido} -3- (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 165 | 7- {D-2-amino-2- [3- (4-butoxybutyloxycarbonyloxy) phenylg -acetamido-3- (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 166 | 7- {D-2-amino-2- [3- (2-carbethoxyethoxycarbonyloxy) - phenyl) -acetamido3-3- (l-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 167 | 7- {D-2-amino-2- [3- (2-acetoxyethoxycarbonyloxy) - phenyl / acetamido {-3- (1-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 168 | 7- {D-2-amino-2- [3- (4-acetoxybutyloxycarbonyloxy) - phenyl) -acetamido3-3- (l-methyl-tetrazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid.

Analogously to Example 134, the compounds of the formula I mentioned in Examples 169 to 203 below can be obtained from the cephalosporanic acids mentioned in Examples 97 to 119 and 121 to 133 by reaction with 1,2,3-triazole-5-thiol: Example compound of formula I. 169 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido] - 3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 170 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] - 3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 171 7-eD-2-amino-2- (3-butyryloxyphenyl) -acetamido,; t- 3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 172 7- (D-2-amino-2 (3-pentanoyloxyphenyl) -acetamido; l- 3- (1, 2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 173 | 7- [D-2-amino-2- (3-hexanoyloxyphenyl) acetamido] 3- (1, 2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 174 | 7- [D-2-amino-2- (3-decanoyloxyphenyl) acetamido] - 3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 175 7-vD-2-amino-2- (3-pivaloyloxyphenyl) -acetamido,> - 3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem- 4-carboxylic acid, 176 | 7- {D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] acetamidog-3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 177 | 7- {D-2-amino-2- [3- (3-chloropropionyloxy) phenyl] - acetamido3-3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 178 7- {D-2-amino-2- [3- (3-bromopropionyloxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, Example compound of formula I. 179 7- {D-2-amino-2- [3- (3-chlorobutyryloxy) phenyl] - acetamido3-3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 180 7- {D-2-amino-2- [3- (2-ethoxyacetoxy) phenyl] - acetamido-3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 181 7- {D-2-amino-2- g3- (3-methoxypropionyloxy) -phenyl, / - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 182 7- {D-2-amino-2- [3- (4-ethoxybutyryloxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 183 7- {D-2-amino-2- [3- (4-butyloxybutyryloxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 184 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 185 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 186 7-fD-2-amino-2- £ 3- (4-acetoxybutyryloxy) phenyl) - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 187 7- {D-2-amino-2- [3- (6-acetoxyhexanoyloxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 188 7- (D-2-amino-2-3- (2-methoxycarbonylacetoxy) -phenyl- acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 189 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 190 | 7- {D-2-amino-2- [3- (2-ethoxycarbonylpentanoyloxy) - phenyl2-acetamido2-3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, Example compound of formula I. 191 | 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) - phenyl) acetamidol-3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 192 7- (D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido) -3 (1, Z, 3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 193 7- {D-2-amino-2- (3-decyloxycarbonyloxyphenyl) - acetamido] -3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 194 | 7- {D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) - acetamido-3- (1,2,3-triazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 195 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] acetamido} -3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 196 | 7- {D-2-amino-2- [3- (2-bromoethoxycarbonyloxy) - phenyll-acetamido7 3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 197 | 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxy) - phenyl2-acetamidot-3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 198 7- {D-2-Amino-2- [3- (2-ethoxyethoxycarbonyloxy) - phenyl) acetamido13-3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 199 | 7- {D-2-amino-2- [3- (4-methoxybutyloxycarbonyloxy) - phenyl2-acetamido {-3- (1,2 ~, 3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 200 | 7- {D-2-amino-2- [3- (4-butyloxybutyloxycarbonyloxy) - phenyl) acetamido (1>2> 3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, Example compound of formula I. 201 | 7- {D-2-amino-2- [3- (2-carbethoxyethoxycarbonyloxy) phenyl2-acetamido} -3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 202 | 7- {D-2-amino-2- [3- (2-acetoxyethoxycarbonyloxy) - phenyl, / - acetamido} -3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 203 | 7- {D-2-amino-2- [3- (4-acetoxybutyloxycarbonyloxy) - phenyl7-acetamido-3- (1,2,3-triazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, Analogously to Example 134, the compounds of the formula I mentioned in Examples 204 to 238 below can be obtained from the cephalosporanic acids mentioned in Examples 97 to 119 and 121 to 133 by reaction with 1,3,4-thiadiazole-2-thiol: Example compound of formula I. 204 | 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 205 | 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 206 | 7- [D-2-amino-2- (3-butyryloxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 207 7-db-2-amino-2- (3-pentanoyloxyphenyl) -acetamido, 7- 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 208 | 7- [D-2-amino-2- (3-hexanoyloxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, Example compound of formula I. 209 | 7- [D-2-amino-2- [3-decanoyloxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 210 | 7- [D-2-amino-2- (3-pivaloyloxyphenyl) acetamido] - 3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem- 4-carboxylic acid, 211 7- {D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 212 | 7- {D-2-amino-2- [3- (3-chloropropionyloxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 213 7- {D-2-amino-2- [3- (3-bromopropionyloxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 214 7- {D-2-Amino-2-er3- (3-chlorobutyryloxy) -phenyl | - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 215 | 7- {D-2-amino-2- [3- (2-ethoxyacetoxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 216 | 7- {D-2-amino-2- [3- (3-methoxypropionyloxy) phenyl] acetam.ido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 217 7-fD-2-amino-2-f3- (4-ethoxybutyrvloxy) -phenyl- acetamido§-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 218 7- {D-2-Amino-2-g3- (4-butyloxybutyryloxy) -phenyl, / - acetamido-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) 3-cephem-4-carboxylic acid, 219 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 220 | 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, Example compound of formula I. 221 | 7- {D-2-amino-2- [3- (4-acetoxybutyryloxy) phenyl] acetamidot-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 222 | 7- {D-2-amino-2- [3- (6-acetoxyhexanoyloxy) phenyl] - acetamido] -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 223 7-CD-2-Amino-2-O- (2-methoxycarbonylacetoxy) -phenyl) - acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 224 | 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamidog-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 225 | 7- {D-2-amino-2- [3- (5-ethoxycarbonylpentanoyloxy) - phenylS -acetamido} -3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 226 | 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) phenyl) -aectamido3-3 (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 227 | 7- {D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido2-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 228 | 7- {D-2-amino-2- (3-decyloxycarbonyloxyphenyl) - acetamido2-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 229 | 7- {D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) - acetamido2-3- (1,3,4-thiadiazolyl-2-mercaptomethyl) - 3-cephem-4-carboxylic acid, 230 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] acetamido} -3- (1,3,4-thiadiazolyl-2-mercapto- methyl] -3-cephem-4-carboxylic acid, 231 7- {D-2-amino-2- [3- (2-bromoethoxycarbonyloxy) - phenyl) acetamido-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, Example compound of formula I. 232 | 7- {D-2-amino-2- [3- (2-methoxyethyloxycarbonyloxy) - phenyl) acetamido-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 233 | 7- {D-2-amino-2- [3- (2-ethoxyethoxycarbonyloxy) - phenyl, / - acetamidot-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 234 | 7- {D-2-amino-2- [3- (4-methoxybutyloxycarbonyloxy) - phenylJ-acetamido} -3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 235 7-fD-2-amino-2- £ 3- (4-butyloxybutyloxycarbonyloxy) - phenylJ-acetamidot-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 236 | 7- {D-2-amino-2- [3- (2-carbethoxyethoxycarbonyloxy) - phenyl2-acetamido} -3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 237 | 7- {D-2-amino-2- [3- (2-acetoxyethoxycarbonyloxy) - phenyl, / - acetamido§-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, 238 | 7- {D-2-amino-2- [3- (4-acetoxybutyloxycarbonyloxy) - phenyl,? - acetamido-3- (1,3,4-thiadiazolyl-2-mercapto- methyl) -3-cephem-4-carboxylic acid, Analogously to Example 134, the compounds of the formula I mentioned in Examples 239 to 273 below can be obtained from the cephalosporanic acids mentioned in Examples 97 to 119 and 121 to 133 by reaction with 2-methyl-1,3,4-thiadiazole-5-thiol : Example connection of the formula .1 239 | 7- [D-2-amino-2- (3-acetoxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 240 | 7- [D-2-amino-2- (3-propionyloxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 241 7- [D-2-amino-2- (3-butyryloxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 242 | 7- [D-2-amino-2- (3-pentanoyloxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 243 7- [D-2-amino-2- (3-hexanoyloxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 244 | 7- [D-2-amino-2- (3-decanoyloxyphenyl) acetamido] - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 245 | 7- [D-2-amino-2- (3-pivaloyloxyphenyl) acetamido] - 3- (2 methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) - 3-cephem-4-carboxylic acid, 246 | 7- [D-2-amino-2- [3- (3-fluoropropionyloxy) phenyl] - acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 247 | 7- [D-2-amino-2- [3- (3-chloropropionyloxy) phenyl] - acetamido] -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 248 7- [D-2-amino-2- [3- (3-bromopropionyloxy) phenyl] - acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 249 | 7- [D-2-amino-2- [3- (3-chlorobutyryloxy) phenyl] - acetamido] -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, Example compound of formula I. 250 7-D-2-amino-2-t3- (2-ethoxyacetoxy) -phenyl- acetamido? -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 251 | 7- {D-2-amino-2- [3- (3-methoxypropionyloxy) phenyl] - acetamido «g-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 252 | 7- {D-2-amino-2- [3- (4-ethoxybutyryloxy) phenyl] - acetamidot-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 253 | 7- {D-2-amino-2- [3- (4-butyloxybutyryloxy) phenyl] acetamido.X-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 254 7- {D-2-amino-2- [3- (2-acetoxyacetoxy) phenyl] - acetamidoj-3- (2-mlethyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 255 | 7- {D-2-amino-2- [3- (3-acetoxypropionyloxy) phenyl] - acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 256 | 7- {D-2-amino-2- [3- (4-acetoxybutyryloxy) phenyl] - acetamidog-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 257 7-fD-2-Amino-2-- -acetoxyhexanoyl oxy) -phenylj) - acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 258 | 7- {D-2-amino-2- [3- (2-methoxycarbonylacetoxy) phenyl] acetamidot-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 259 | 7- {D-2-amino-2- [3- (2-ethoxycarbonylacetoxy) phenyl] - acetamido} -3- (2-methyl ~ 1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 260 7- {D-2-amino-2- [3- (5-ethoxycarbonylpentanoyloxy) - phenyl) acetamido1-3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 261 7- {D-2-amino-2- [3- (5-hydroxycarbonylpentanoyloxy) - phenyl] acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, Example compound of formula I. 262 7- [D-2-amino-2- (3-butyloxycarbonyloxyphenyl) - acetamido] -3- [2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 263 7- £ D-2-amino-2- (3-decyloxycarbonyloxyphenyl) acetamido2-3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 264 7- [D-2-amino-2- (3-isopropyloxycarbonyloxyphenyl) - acetamido, / - 3- (2-methyl-1,3,4-thiadiazolyl-5-mercapto- methyl) -3-cephem-4-carboxylic acid, 265 7- {D-2-amino-2- [3- (2-chloroethoxycarbonyloxy) - phenyl] acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 266 7- {D-2-amino-2- [3- (2-bromoethoxycarbonyloxy) - phenyl2-acetamidot-3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 267 7- {D-2-amino-2- [3- (2-methoxyethoxycarbonyloxy) - phenylt-acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 268 7- {D-2-amino-2- g3- (2-ethoxyethoxycarbonyloxy) - phenyl] acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 269 7- {D-2-amino-2- [3- (4-methoxybutyloxycarbonyloxy) - phenyl] acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 270 7-tD-2-amino-2-g3- (4-butyloxybutyloxycarbonyloxy) - phenyl | -acetamido3-3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 271 7-fD-2-Amino-2- £ 3- (2-carbethoxyethoxycarbonyloxy) - phenylJ-acetamido-3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 272 7- {D-2-amino-2- [3- (2-acetoxyethoxycarbonyloxy) - phenylD-acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid, 273 7- {D-2-amino-2- 3- (4-acetoxybutyloxycarbonyloxy) - phenyl] acetamido} -3- (2-methyl-1,3,4-thiadiazolyl-5- mercaptomethyl) -3-cephem-4-carboxylic acid.

Example 274 3.1 g of 7-amino-3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid are suspended in 50 ml of dry acetonitrile, gives 1 g of triethylamine and 2 ml of N, N-dimethylaniline to, lets stand for 10 minutes at room temperature, then adds within 15 minutes at 5 ° C 2.8 g of D, L-2-amino-2- (3-propionyloxyphenyl) acetylchloride hydrochloride (available from a suspension of D, L-2-amino-2- (3-propionyloxyphenyl) acetic acid in dry dioxane by successive introduction of dry phosgene and dry HCl gas), the mixture is stirred for 1 hour at 12 ° C., while stirring 40 ml of water, add Na2CO3 until a pH value of 2.5 is reached, separate the organic Phase off, bring the aqueous phase to a pH value of 2, wash with diethyl ether, brings the aqueous phase to pH 4 and concentrates until it becomes cloudy. One lets Stand at 5 ° for 24 hours, filter and dry the precipitate. 7-D, L-2-amino-2- (3-propionyloxyphenyl) -acetami are obtained do) -3- (2-methyl-1,3,4-thiadiazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid.

Example 275 2.15 g of 2-D-BOC-amido-2-e- (5-methoxycarbonylpentanoyl) phenyl2-acetic acid are added and 0.69 ml of triethylamine in 20 ml of THF at -10 ° C, 0.65 ml of isobutyl chloroformate, drops to the solution of the mixed carbonic anhydride thus prepared in situ 2.07 g of the triethylammonium salt of 7-amino-3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid, dissolved in 18 ml of 50% aqueous THF, the mixture is stirred at 5 ° C. for 1 hour 1 hour at room temperature, the THF is distilled off, 30 ml of water are added to the residue, extracted with 10 ml of ethyl acetate, bring the aqueous phase to pH = 3 with HOl, filtered and extracted the filtrate twice with 25 ml of ethyl acetate each time. the organic Phase is washed with water, dried over sodium sulfate and the solvent distilled off. After treating the oily residue with diethyl ether / petroleum ether one obtains 7-tD-2-BOC-amido-2-g3- (5-methoxycarbonylpentanoyl) -phenyl2-acetamido * S-3- (1,2,3-triazolyI-5-mercaptomethyl) -3-cephem-4- carboxylic acid, from it directly analogously to Example 2, the trifluoroacetate of 7-fD-2-amino-2- £ 3- (5-methoxycarbonylpentanoyl) -phenylacetamidoI-3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid and from this, analogously to Example 3, the free 7-fD-2 amino-2- [3- (5-methoxycarbonylpentanoyl) phenyl] acetamido} -3- (1,2,3-triazolyl-5-mercaptomethyl) -3-cephem -4-carboxylic acid.

Example 276 5.93 g of 7-uD-2-BOC-amido-2- (3-hydroxyphenyl) acetamido-3- (1-methyltetrazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid (obtainable analogously to Example 275 from the triethylammonium salt of 7-amino-3- (1-methyltetrazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid and 2-D-BOC-amido-2- (3-hydroxyphenyl) acetic acid) are dissolved in 150 ml of dichloromethane solved. After addition of 6.9 potassium carbonate, the mixture is added dropwise at 0-5 ° C. with stirring 1.8 g adipic acid monomethyl ester monochloride, dissolved in a little dichloromethane, to if the dichloromethane is distilled off after 20 minutes, the residue is taken up in ethyl acetate on, extracted with water, brings the aqueous phase to pH = 3 with hydrochloric acid, extracted with ethyl acetate, the organic phase is dried over sodium sulfate and distilled the solvent is removed and the residue is 7- {D-2-BOC-amido-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl) acetamido-3- (1-methyltetrazolyl-s mercaptomethyl) -3-cephem-4-carboxylic acid.

Analogously to Example 2, the BOC group is obtained by cleaving off with trifluoroacetic acid the trifluoroacetate of 7-fD-2-amino-2- [3- (5-methoxycarbonylpentanoyloxy) -phenyl] -acetamido} -3- (1-methyltetrazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid.

Analogously to Example S., the trifluoroacetate is obtained by reaction with NaOH the free 7- {D-2-amino-2- [3-methoxycarbonylpentanoyloxy) -phenyl-acetamido-3- (1-methyltetrazolyl-5-mercaptomethyl) -3-cephem-4-carboxylic acid.

Example 277 Analogously to Example 276, 7- [D-2-BOC-amido-2- (3-hydroxyphenyl) acetamido] -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem-4 is obtained -carboxylic acid by reacting with adipic acid monomethyl ester monochloride the 7-LD-2-amino-2-t3- (5-methoxycarbonylpentanoyloxy) Y phenyl / acetamido} -3- (1,3,4-thiadiazolyl-2-mercaptomethyl) -3-cephem-4-carboxylic acid available.

Example 278 419 mg of 7- [2-D-amino-2- (3-propionyloxyphenyl) acetamido] -MCC are dissolved and 42 mg of NaHCO3 in 6 ml of water, stirred for 30 minutes at room temperature and obtained after freeze-drying the solution, the sodium salt of 7- [2-D-amino-2- (3-propionyloxyphenyl) acetamido] -MCC.

The other compounds of the formula I are analogous, in particular those mentioned in the above examples by reaction with NaHCO 3 the corresponding Sodium salts or the corresponding salts can be obtained by reacting with other bases.

The active ingredients of the formula I can be according to methods that are derived from the Literature are known to process lph pharmaceutical preparations, such as the The following examples show: Example A: Ampoules A solution of 100 g of 7- (2-amino-2- (3-propionyloxyohenyl) acetamido] cephalosporanic acid, sodium salt is dissolved in 0.3 l of double-distilled water, sterile filtered, in ampoules bottled, lyophilized under sterile conditions and sealed under sterile conditions. Every Ampoule contains 1 g of active ingredient.

The solution ampoules are behaved by adding 50 g of lidocaine hydrochloride Dissolves in 3 l of double-distilled water and, after sterile filtration, in ampoules which are sterilized at 120 ° for 20 minutes. Each solution ampoule contains 50 mg lidocaine hydrochloride in 3 ml water, Example B: Tablets A mixture Consists of 1Q0 g of the sodium salt of 7- (2-Amino-2- (3-propionyloxyphenyl) acetamido] -MCC, 500 g milk sugar, 180 g wheat starch, 10 g cellulose powder and 10 g magnesium stearate is compressed into tablets in the usual way, so that each tablet 50 mg des Contains active ingredient.

Claims (8)

Claims 1. Compounds of the general formula I RCOO-m-C6H4-CH (NHZ) C0 CH2R1 CH2R1 wherein COOH RH, alkyl with 1-9 carbon atoms or alkyl substituted one or more times by F, Cl, Br, COOH, alkoxy with 1-4 atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2-5 carbon atoms with 1-9 carbon atoms, alkoxy with 1-10 carbon atoms or one or more times with F, Cl, Br, alkoxy with 1-4 atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2-5 carbon atoms -Atoms-substituted alkoxy with 1 - 10 carbon atoms, R1 H, acetoxy or -S-Het, and Het 1,2,3-triazol-5-yl, 1-methyl-tetrazol-5-yl, 1,3, Means 4-thiadiazol-2-yl or 2-methyl-1,3,4-thiadiazol-5-yl, as well as their easily cleavable esters and their physiologically acceptable salts. 2. 7-eD-2-amino-2- (3-propionyloxyphenyl) -acetamidoS-3-methyl-3-cephem-4-carboxylic acid. 3. 7- {D-2-amino-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl] acetamido} -3-methyl-3-cephem-4-carboxylic acid. 4. 7- [D-2-aminoi-2- (3-propionyloxyphenyl) acetamido] caphalosporan acid. 5. 7- {D-2-amino-2- [3- (5-methoxycarbonylpentanoyloxy) phenyl] acetamido} cephalosporanic acid. 6, process for the preparation of a compound of general formula I. RCOO-m-c6H4-CH (NH2) CONH CON »{:} ¼9H2R1 wherein 0 is COOH RH, alkyl with 1 - 9 carbon atoms or one or more times with F, Cl, Br, COOH, alkoxy with 1 - 4 carbon atoms, alkanoyloxy with 1 - 4 carbon atoms or carboalkoxy with 2 - 5 carbon atoms substituted alkyl with 1-9 carbon atoms, alkoxy with 1-10 carbon atoms or one or more times by F, Cl, Br, alkoxy with 1-4 carbon atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2 - 5 carbon atoms substituted alkoxy with 1 - 10 carbon atoms, R1 H, acetoxy or -S-Het, and Het 1,2,3-triazol-5-yl, 1-methyl-tetrazol-5-yl, 1,3; 4-Thiadiazol-2-yl or 2-methyl-1,3,4-thiadiazol-5-yl, and their easily cleavable esters and their physiologically acceptable salts, characterized in that a compound of the general formula II in which R1 has the meaning given above, or one of its functional derivatives with a compound of the general formula III RCOO-m-C6H4-CH (NH2) COOH III in which R has the meaning given above, or one of its functional derivatives or an acid addition salt of these compounds converts, or that a compound of the general formula IV R2C00-m-C6H4-CH (NH2) CONH SCHR1 IV wherein COOH C00H R2 is alkenyl with 2-9 carbon atoms or substituted one or more times by F, Cl, Br, C00H, alkoxy with 1-4 carbon atoms, alkanoyloxy with 1-4 carbon atoms or carboalkoxy with 2-5 carbon atoms Alkenyl with 2 - 9 carbon atoms, alkenyloxy with 2 - 10 carbon atoms or one or more times with F, Cl, Br, alkoxy with 1 - 4 carbon atoms, alkanoyloxy with 1 - 4 carbon atoms or carboalkoxy with 2 - 5 C-Atomenjsubstituierter alkenyloxy with 2-10 C-atoms and R1 has the meaning given above, with a hydrogenating agent or with chlorine or bromine, or that one in a compound which otherwise corresponds to the formula I, but in which an NH2 group is present in a functionally modified form, or one of its easily cleavable esters or one of its physiologically tolerable salts, this NH2 group is set free by treatment with hydrolyzing or hydrogenolyzing agents, and / or in a compound of the formula I obtained or one of their easily cleavable esters or one of their Physiologically acceptable salts convert a radical R1 into another radical R1 by reaction with reducing or hydrogenolysing agents or by reaction with a thiol HS-Het and / or that one in a compound of formula I obtained or one of its easily cleavable esters or one of its physiologically harmless salts converts the radical R into another radical R by reacting with alkylating or solvolyzing agents and / or converting a compound of the formula I into one of its easily cleavable esters by reacting with an esterifying agent, and / or converting a compound of the Formula I is set free from one of its easily cleavable esters by reaction with a hydrolyzing agent and / or that a compound of the formula I is converted into one of its physiologically acceptable salts by reaction with an acid or a base and / or that a compound of Formula I by reacting with a base or an acid sets one of its salts free. 7. Pharmaceutical preparation, characterized by a content on at least one compound of the general formula I and / or one of its physiological harmless salts and / or one of their easily cleavable esters. 8. Process for the production of pharmaceutical preparations, thereby characterized in that at least one compound of formula I and / or at least one of its physiologically harmless salts and / or at least one of its light salts cleavable ester, optionally together with at least one solid, liquid or semi-liquid auxiliary or carrier and optionally together with at least brings another active ingredient into a suitable dosage form.