Peptide process for preparation thereof and use thereof

Abstract

The invention deals with novel peptides useful for the therapeutic treatment of infectious diseases caused by pathogenic microorganisms. Included is the peptide FR900156 having the structure: ##STR1## as well as the peptides of the structure ##STR2## wherein R 1 is acyl; R b 1 is hydrogen, methyl, isopropyl, hydroxymethyl, protected hydroxymethyl or benzyl; R 2 is hydrogen, carboxy, protected carboxy, or a group of the formula: ##STR3## wherein R a 2 is mono- or di-carboxy lower alkyl or ar(carboxy) lower alkyl whose aryl moiety may be substituted by hydroxy, R b 2 is hydrogen or lower alkyl; R p and R q are each hydrogen, carboxy, protected carboxy, with proviso that when one of R 2 and R q is hydrogen, then the other is carboxy or protected carboxy; R r is hydrogen or amino protective group; m is an integer 1 to 3, and n is 1 .Iadd.provided that when R 1 is benzyloxycarbonyl R 5 1 is methyl, m is an integer 2 and n is an integer 1, then R 2 is not protected carboxy, and .Iaddend.provided that when R 1 is .[.hydrogen,.]. t-butoxycarbonyl or N-acetylmuramyl, R b 1 is methyl, m is an integer 2 and n is an integer 1, then R 2 is hydrogen, protected carboxy or a group of the formula: ##STR4## wherein R a 2 is mono- or di-carboxy lower alkyl having 1 and 3 to 6, carbon atoms, .[.α-carboxyethyl,.]. .Iadd.--CH 2 --CH 2 --COOH, .Iaddend.ar(carboxy) lower alkyl whose aryl moiety may be substituted by hydroxy and R b 2 is as defined above, or its pharmaceutically acceptable salt.

We claim: .[.1. A compound of the formula:.]. ##STR379## .[.wherein 
     
        above, or its pharmaceutically acceptable salt..]. .[.2.  A compound according to the claim 1, wherein R 1  is acyl,   R b   1  is hydrogen, methyl, isopropyl, hydroxymethyl or benzyl,   R 2  is hydrogen, carboxy or a group of the formula:.]. ##STR382## .[.wherein R a   2  and R b   2  is as defined in claim 1,   R p  and R q  are each hydrogen or carboxy, with proviso that when one of R 2  and R q  is hydrogen, then the other is carboxy, and   
     
     
       R r  is hydrogen..]. .[.3.  A compound according to the claim 1, wherein n is an integer 1 and   
     
     
       m is an integer 1..]. .[.4.  A compound according to claim 2 wherein n is 1 
     
     
        and m is 1..]. .[.5.  A compound according to the claim 1, wherein n is an integer 1 and   
     
     
       m is an integer 2..]. .[.6.  A compound according to claim 2, wherein n is 
     
     
        1 and m is 2..]. .[.7.  A compound according to the claim 1, wherein n is an integer 1 and   
     
     
       m is an integer 3..]. .[.8.  A compound according to claim 2 wherein n is 1 
     
     
        and m is 3..]. .[.9.  A compound according to the claim 1, wherein R 2  is hydrogen or protected carboxy,   R p  and R q  are each hydrogen or protected carboxy, with proviso that when one of R 2  and R q  is hydrogen, then the other is   
     
     
        protected carboxy..]. .[.10.  A compound according to the claim 1, wherein the protected carboxy for R 2 , R p  and/or R q  is esterified 
     
     
        carboxy..]. 11. A compound of the formula: ##STR383## 
     
     
         12. A compound of the formula: ##STR384## 
     
     
         .Iadd.13.  A compound of the formula: ##STR385## wherein R 1  is an aliphatic acyl radical which is unsubstituted alkanoyl or alkenoyl or is alkanoyl of at least two carbon atoms or alkenoyl substituted by amino, halogen, hydroxy, lower alkoxy, or lower alkanoylamino; R b   1  is hydrogen, methyl, isopropyl, hydroxymethyl, protected hydroxymethyl or benzyl;   R 2  is hydrogen, carboxy, protected carboxy, or a group of the formula: ##STR386## wherein R a   2  is mono- or di-carboxy lower alkyl or ar(carboxy)lower alkyl whose aryl moiety is unsubstituted or is substituted by hydroxy, R b   2  is hydrogen or lower alkyl;   R p  is hydrogen, carboxy, or protected carboxy,   R q  is carboxy or protected carboxy;   R r  is hydrogen or amino protective group;   m is an integer 1 to 3; and   n is 1,   
     
     
       or its pharmaceutically acceptable salt. .Iaddend. .Iadd.14.  A compound of the formula: ##STR387## wherein R 1  is acyl, R b   1  is hydrogen, methyl, isopropyl, hydroxymethyl or benzyl,   R 2  is hydrogen, carboxy or a group of the formula: ##STR388## R a   2  is mono- or di-carboxy lower alkyl or ar(carboxy)lower alkyl whose aryl moiety is unsubstituted or is substituted by hydroxy, R b   2  is hydrogen or lower alkyl;   R p  is hydrogen or carboxy;   R q  is carboxy;   R r  is hydrogen.   m is an integer 1 to 3; and   n is 1, provided that when R 1  is t-butoxycarbonyl or N-acetylmuramyl, R b   1  is methyl, m is an integer 2 and n is an integer 1, then R 2  is hydrogen, or a group of the formula: ##STR389## wherein R a   2  is mono- or di-carboxy lower alkyl having 1 and 3 to 6 carbon atoms, -CH 2  -CH 2  -COOH, ar(-carboxyl)lower alkyl whose aryl moiety is unsubstituted or is substituted by hydroxy and R b   2  is as defined above, or its pharamaceutically acceptable   
     
     
        salt. .Iaddend. .Iadd.15.  A compound according to the claim 13, wherein n is an integer 1 and m is an integer 1. .Iaddend. .Iadd.16. A compound according to claim 14 wherein n is 1 and m is 1. .Iaddend. .Iadd.17. A compound according to the claim 13, wherein n is an integer 1 and m is an integer 2. .Iaddend. .Iadd.18. A compound according to claim 14, wherein n 
     
     
        is 1 and m is 2. .Iaddend. .Iadd.19.  A compound according to the claim 13, wherein n is an integer 1 and m is an integer 3. .Iaddend. .Iadd.20. A compound according to claim 14, wherein n is 1 and m is 3. .Iaddend. .Iadd.21. A compound according to the claim 13, wherein R 2  is hydrogen or protected carboxy, R p  is hydrogen or protected carboxy, and R q  is protected carboxy. .Iaddend. .Iadd.22. A compound according to the claim 13, wherein the protected carboxy for at least one of R 2 , R p  and R q  is esterified carboxy. .Iaddend.