O-acyl derivatives of antibiotic EM-49

• US 3,941,762 A
• Filed: 07/08/1974
• Issued: 03/02/1976
• Est. Priority Date: 05/07/1973
• Status: Expired due to Term

• Current Assignee: E R Squibb & Sons Incorporated
• Original Assignee: E R Squibb & Sons Incorporated
• Inventors: Parker, William Lawrence
• Primary Examiner(s): Gotts, Lewis
• Assistant Examiner(s): Suyat, Reginald J.
• Application Number:
  US05/486,557
• Time in Patent Office: 603 Days
• Field of Search: 424/115, 260/112.5, 195/29
• US Class Current: 530/318
• CPC Class Codes: C07K 7/60 the cyclisation occurring through the 4-amino group of 2,4-diamino-butanoic acid
• CPC Class Codes: Y10S 435/835 Bacillus circulans

Abstract

Antibiotic EM-49, an antimicrobially active material obtained from the microorganism Bacillus circulans ATCC 21656, is chemically treated to acylate the hydroxyl group, thereby obtaining O-acyl derivatives which are effective against a variety of bacteria and fungi.

Claims

1. The O-acetyl derivative of antibiotic EM-49 and acid salts thereof, the hydrochloride having the infrared absorption spectrum as in FIG. 5, the NMR spectrum as in FIG. 6, the approximate elemental analysis of anhydrous material:

C, 51.10;

H, 8.00;

N, 14.90;

Cl, 11.60;

the approximate empirical formula C₅₂ H₉₇ N₁₃ O₁₁ Cl₄ and an approximate molecular weight of 1222.

2. The hydrochloride of the product of claim 1.

3. The tetra(benzyloxycarbonyl) derivative of antibiotic EM-49 having the infrared absorption as in FIG. 1, the NMR spectrum as in FIG. 2, the approximate elemental analysis of anhydrous material:

C, 61.27;

H, 6.69;

N, 11.37;

the approximate empirical formula C₈₂ H₁₁₅ N₁₃ O₁₈ and an approximate molecular weight of 1571.

4. The tetra(benzyloxycarbonyl)-O-acetyl derivative of antibiotic EM-49, having the infrared absorption spectrum as in FIG. 3, the NMR spectrum as in FIG. 4, the approximate elemental analysis of anhydrous material:

C, 61.63;

H, 7.25;

N, 11.68;

the approximate empirical formula C₈₄ H₁₁₇ N₁₃ O₁₉ and an approximate molecular weight of 1613, and acid salts thereof.

5. The O-butyryl derivative of antibiotic EM-49 and acid salts thereof, the hydrochloride having the infrared absorption spectrum as in FIG. 7, the approximate elemental analysis of anhydrous material, as the hydrochloride:

C, 52.45;

N, 14.40;

Cl^-, 11.17;

the approximate empirical formula C₅₄ H₁₀₁ N₁₃ O₁₁ Cl₄ and an approximate molecular weight of 1250.

6. The O-hexanoyl derivative of antibiotic EM-49, and acid salts thereof, having the infrared absorption spectrum as in FIG. 9, the approximate elemental analysis of anhydrous material:

C, 59.83;

N, 15.76;

the approximate empirical formula C₅₆ H₁₀₁ N₁₃ O₁₁ and an approximate molecular weight of 1132.

7. The O-octanoyl derivative of antibiotic EM-49, and acid salts thereof, the hydrochloride having the infrared spectrum as in FIG. 12, the approximate elemental analysis:

C, 51.97;

H, 8.37;

N, 12.96;

Cl^-, 10.12;

the approximate empirical formula C₅₈ H₁₀₉ N₁₃ O₁₁ Cl₄ and an approximate molecular weight of 1306.

8. A compound of the formula ##EQU3## wherein Dab is 2,4-diaminobutyric acid, Y is L-leucine or L-phenylalanine;

X is ##EQU4## R¹ is C₇ H₁₅ or C₈ H₁₇ ; and

R² is lower alkanoyl, and acid salts thereof.

9. A compound as in claim 8 wherein Y is L-leucine.

10. A compound as in claim 8 wherein Y is L-phenylalanine.

11. A compound as in claim 8 wherein R² is acetyl.

12. A compound as in claim 8 wherein R² is butyryl.

13. A compound as in claim 8 wherein R² is hexanoyl.

14. A compound as in claim 8 wherein R² is octanoyl.

15. Acid addition salt of a compound as in claim 13.

16. Hydrochloride of a compound as in claim 13.

17. A compound as in claim 9 wherein R¹ is C₇ H₁₅ and R² is acetyl.

18. A compound as in claim 9 wherein R¹ is C₈ H₁₇ and R² is acetyl.

19. A compound as in claim 9 wherein R is C₇ H₁₅ and R² is butyryl.

20. A compound as in claim 9 wherein R¹ is C₈ H₁₇ and R² is butyryl.

21. A compound as in claim 9 wherein R¹ is C₇ H₁₅ and R² is hexanoyl.

22. A compound as in claim 9 wherein R¹ C₈ H₁₇ and R² is hexanoyl.

23. A compound as in claim 9 wherein R¹ is C₇ H₁₅ and R² is octanoyl.

24. A compound as in claim 9 wherein R¹ is C₈ H₁₇ and R² is octanoyl.

25. A compound as in claim 10 wherein R¹ is C₇ H₁₅ and R² is acetyl.

26. A compound as in claim 10 wherein R¹ is C₈ H₁₇ and R² is acetyl.

27. A compound as in claim 10 wherein R¹ is C₇ H₁₅ and R² is butyryl.

28. A compound as in claim 10 wherein R¹ is C₈ H₁₇ and R² is butyryl.

29. A compound as in claim 10 wherein R¹ is C₇ H₁₅ and R² is hexanoyl.

30. A compound as in claim 10 wherein R¹ is C₈ H₁₇ and R² is hexanoyl.

31. A compound as in claim 10 wherein R¹ is C₇ H₁₅ and R² is octanoyl.

32. A compound as in claim 10 wherein R¹ is C₈ H₁₇ and R² is octanoyl.

33. A compound as in claim 10 wherein X is 2-hexanoyloxy-8-methyldecanoyl.