Derivatives of A-21978C cyclic peptides

Abstract

A-21978C cyclic peptide derivatives of the formula ##STR1## wherein R is hydrogen, a specified aminoacyl or N-alkanoylaminoacyl group, 8-methyldecanoyl, 10-methyldodecanoyl, 10-methylundecanoyl, the specific C 10 -alkanoyl group of A-21978C 0 or the specific C 12 -alkanoyl groups of A-21978C factors C 4 and C 5 or an amino-protecting group; and R 1 is hydrogen, an amino-protecting group, or a specified aminoacyl or N-alkanoylaminoacyl group; provided that, when R is other than aminoacyl or N-alkanoylaminoacyl, R 1 must be aminoacyl or N-alkanoylaminoacyl; and, when R 1 is an amino-protecting group, R must be aminoacyl or N-alkanoylaminoacyl; and the salts thereof, are useful as antibacterial agents or as intermediates to antibacterial agents.

I claim: 
     
       1. An A-21978C cyclic peptide derivative of the formula: ##STR75## wherein R is hydrogen 8-methyldecanoyl, 10-methyldodecanoyl, 10-methylundecanoyl, the specific C 10  -alkanoyl group of A-21978C 0  or the specific C 12  -alkanoyl groups of A-21978C factors C 4  and C 5 , an amino-protecting group, an aminoacyl group of the formula ##STR76## wherein Q is C 1  -C 16  alkylene, or an N-alkanoylamino acyl group of the formula ##STR77## wherein: 
     
     
       W is a divalent aminoacyl radical of the formula: ##STR78##  wherein A is C 1  -C 10  alkylene or C 5  -C 6  cycloalkylene; ##STR79##  wherein R 3  is hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indole-methyl, phenyl, benzyl, or substituted phenyl or substituted benzyl in which the benzene ring thereof is substituted with chloro, bromo, iodo, nitro, C 1  -C 3  alkyl, hydroxy, C 1  -C 3  -alkoxy, C 1  -C 3  alkylthio, carbamyl, or C 1  -C 3  alkylcarbamyl; ##STR80## wherein X is hydrogen chloro, bromo, iodo, amino, nitro, C 1  -C 3  alkyl, hydroxy, C 1  -C 3  alkoxy, mercapto, C 1  -C 3  alkylthio, carbamyl, or C 1  -C 3  alkylcarbamyl; ##STR81## wherein X 1  is chloro, bromo, iodo, amino, hydroxy, C 1  -C 3  alkyl or C 1  -C 3  alkoxy; ##STR82## wherein B is a divalent radical of the formula: --(CH 2 ) n  -- and n is an integer from 1 to 3; --CH═CH--; --CH═CH--CH 2  --; or ##STR83## R 2  is C 1  -C 17  alkyl or C 2  -C 17  alkenyl; and R 1  is hydrogen, an amino-protecting group, an aminoacyl group of the formula ##STR84##  as herein defined, or an N-alkanoylaminoacyl group of the formula ##STR85##  as herein defined; provided that, when R is other than aminoacyl or N-alkanoylaminoacyl, R 1  must be aminoacyl or N-alkanoylaminoacyl; and, when R 1  is an amino-protecting group, R must be aminoacyl or N-alkanoylaminoacyl; and the salts thereof. 
     
     
       2. A compound of claim 1 wherein R is ##STR86## A is C 1  -C 10  alkylene and R 2  is straight chain C 1  -C 17  alkyl. 
     
     
       3. A compound of claim 2 wherein R 1  is hydrogen. 
     
     
       4. The compound of claim 3 wherein R is 5-[N-(n-dodecanoyl)amino]-n-pentanoyl. 
     
     
       5. The compound of claim 3 wherein R is 11-[N-(n-dodecanoyl)amino]-n-undecanoyl. 
     
     
       6. The compound of claim 3 wherein R is 11-[N-(n-heptanoyl)amino]-n-undecanoyl. 
     
     
       7. A compound of claim 1 wherein R is ##STR87## X is hydrogen and R 2  is straight chain C 1  -C 17  alkyl. 
     
     
       8. A compound of claim 7 wherein R 1  is hydrogen. 
     
     
       9. The compound of claim 8 wherein R is p-[N-(n-dodecanoyl)amino]benzoyl. 
     
     
       10. The compound of claim 8 wherein R is m-[N-(n-dodecanoyl)amino]benzoyl. 
     
     
       11. The compound of claim 8 wherein R is p-[N-(n-tetradecanoyl)amino]benzoyl. 
     
     
       12. A compound of claim 1 wherein R is ##STR88## X 1  is chloro, bromo, iodo, amino, C 1  -C 3  alkyl, hydroxy, or C 1  -C 3  alkoxy, and R 2  is straight chain C 1  -C 17  alkyl. 
     
     
       13. A compound of claim 12 wherein R 1  is hydrogen. 
     
     
       14. The compound of claim 13 wherein R is 5-amino-4-[N-(n-dodecanoyl)amino]-2-hydroxybenzoyl. 
     
     
       15. The compound as defined in claim 13 wherein R is 3-[N-(n-dodecanoyl)amino]-2,5-dichlorobenzoyl. 
     
     
       16. The compound of claim 1 wherein R is p-[N-(n-dodecanoyl)amino]phenylacetyl and R 1  is hydrogen. 
     
     
       17. The compound of claim 1 wherein R is p-[N-(n-dodecanoyl)amino]cinnamoyl and R 1  is hydrogen. 
     
     
       18. The compound of claim 1 wherein R is p-[N-(n-dodecanoyl)amino]hippuryl and R 1  is hydrogen. 
     
     
       19. The compound of claim wherein R is 2-[N-(n-dodecanoyl)amino]nicotinoyl and R 1  is hydrogen. 
     
     
       20. A compound of claim 1 wherein R is ##STR89## R 2  is C 1  -C 17  alkyl and R 3  is phenyl, benzyl or 3-indolemethyl. 
     
     
       21. A compound of claim 20 wherein R 1  is hydrogen. 
     
     
       22. The compound of claim 21 wherein R is N-(n-dodecanoyl)phenylalanyl. 
     
     
       23. The compound of claim 21 wherein R is N-(n-octanoyl)phenylalanyl. 
     
     
       24. The compound of claim 21 wherein R is N-(n-nonanoyl)phenylalanyl. 
     
     
       25. The compound of claim 21 wherein R is N-(n-decanoyl)phenylalanyl. 
     
     
       26. The compound of claim 21 wherein R is N-(n-undecanoyl)phenylalanyl. 
     
     
       27. The compound of claim 21 wherein R is N-(n-tridecanoyl)phenylalanyl. 
     
     
       28. The compound of claim 21 wherein R is N-(n-tetradecanoyl)phenylalanyl. 
     
     
       29. The compound of claim 21 wherein R is N-(n-hexanoyl)tryptophanyl. 
     
     
       30. The compound of claim 21 wherein R is N-(n-dodecanoyl)tryptophanyl. 
     
     
       31. The compound of claim 20 wherein R is N-(n-hexanoyl)tryptophanyl. 
     
     
       32. The compound of claim 32 wherein R 1  is 8-methyldecanoyl. 
     
     
       33. The compound of claim 31 wherein R 1  is 10-methyldodecanoyl. 
     
     
       34. The compound of claim 31 wherein R 1  is 10-methylundecanoyl.