A54145 antibiotics and process for their production
AssigneeEli Lilly and Company
InventorsLaVerne D. Boeck, David S. Fukuda, Jon S. Mynderse, Marvin M. Hoehn, Ralph E. Kastner, Harold R. Papiska
Life of this patent
Estimating the term…
Abstract
New peptide antibiotic A54145, individual A54145 components A, A.sub.1, B, B.sub.1, C, D, E and F and their pharmaceutically acceptable salts, are useful antibacterial agents which also improve growth performance in animals, especially poultry. Biologically pure cultures of the A54145-producing Streptomyces fradiae cultures NRRL 18158, NRRL 18159 and NRRL 18160 cultures and methods of making antibiotic A54145 using those cultures are also provided.
Claims25
A54145A, which has the following characteristics:
- Mol. Wt.:
- 1643
- Mol. Formula:
- C.sub.72 H.sub.109 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1644.7778, Calcd. for C.sub.72 H.sub.110 N.sub.17 O.sub.27 :
- 1644.7757
- UV (EtOH) .lambda..sub.max :
- 219 nm (.epsilon. 35,000), 280 (.epsilon. 5,250), shoulder 288 (.epsilon. 4,600)
- Optical Rotation:
- [.alpha]sub.589.sup.25.degree. C. No Rotation (CH.sub.3 OH);
- [.alpha]sub.365.sup.25.degree. C. -14.0.degree. (c 1.0, CH.sub.3 OH)
- Amino-acid Analysis:
- Asp 973(2), Thr 441(1), Glu 1056(2), Gly 528(1), Ala 549(1), Ile 469(1), Trp 465(1)
- .sup.1 H NMR (360 MHz):
- FIG. 1;
- or a pharmaceutically acceptable salt of A54145A.
A54145B, which has the following characteristics:
- Mol. Wt.:
- 1657
- Mol. Formula:
- C.sub.73 H.sub.111 N.sub.17 O.sub.27 ;
- High Resolution FABMS(M+H):
- Found:
- 1658.7954, Calcd. for C.sub.73 H.sub.112 N.sub.17 O.sub.27 :
- 1658.7914
- UV (EtOH) .lambda..sub.max :
- 220 nm (.epsilon. 41,854), 281 (.epsilon. 5,613), 289 (.epsilon. 5,084)
- IR (KBr):
- FIG. 9;
- Optical Rotation:
- [.alpha]sub.589.sup.25.degree. C. =-8.55.degree. (c 0.47, H.sub.2 O);
- [.alpha]sub.365.sup..congruent..degree. C. =-36.32.degree. (c 0.47, H.sub.2 O)
- Amino-acid Analysis:
- Asp 1039(2), Thr 466(1), Glu 564(1), Gly 528(1), Ala 525(1), Ile 491(1), Lys 514(1), Trp 491(1), 3-Me-Glu 512(1).
- .sup. H NMR (360 MHz):
- FIG. 2;
- or a pharmaceutically acceptable salt of A54145B.
A54145C, which has the following characteristics:
- Mol. Wt.:
- 1657
- Mol. Formula:
- C.sub.73 H.sub.111 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1658.7905, Calcd. for C.sub.73 H.sub.112 N.sub.17 O.sub.27 :
- 1658.7914
- UV (EtOH) .lambda..sub.max :
- 219 nm (.epsilon. 29,500), 281 (.epsilon. 4,200), 288 (.epsilon. 3,600)
- Amino-acid Analysis:
- Asp 934(2), Thr 414(1), Glu 594(1), Gly 501(1), Ala 459(1), Val 359(1), Lys 451(1), 3-MG 487(1), Trp 308(1).
- .sup.1 H NMR (360 MHz):
- FIG. 3;
- or a pharmaceutically acceptable salt of A54145C.
A54145D, which has the following characteristics:
- Mol. Wt.:
- 1657
- Mol. Formula:
- C.sub.73 H.sub.111 N.sub.17 O.sub.27;
- High Resolution FABMS(M+H):
- Found:
- 1658.7913, Calcd. for C.sub.73 H.sub.112 N.sub.17 O.sub.27 :
- 1658.7914
- UV (EtOH) .lambda..sub.max :
- 219 nm (.epsilon. 37,500), 280 (.epsilon. 5,200), 288 (.epsilon. 4,500)
- Amino-acid Analysis:
- Asp 1011(2), Thr 427(1), Glu 967(2), Gly 515(1), Ala 487(1), Ile 434(1), Lys 543(1), Trp 577(1)
- .sup. H NMR (270 MHz):
- FIG. 4;
- or a pharmaceutically acceptable salt of A54145D.
A54145E, which has the following characteristics:
- Mol. Wt.:
- 1671
- Mol. Formula:
- C.sub.74 H.sub.113 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1672.8065, Calcd. for C.sub.74 H.sub.114 N.sub.17 O.sub.27 :
- 1672.8069
- UV (EtOH) .lambda..sub.max :
- 221 nm (.epsilon. 29,714), 278 (.epsilon. 4,577), 289 (4,044)
- Amino-acid Analysis:
- Asp 826(2), Thr 367(1), Glu 494(1), Gly 437(1), Ala 422(1), Ile 378(1), Lys 410(1), Trp 387(1), 3-MG 437(1)
- .sup.1 H NMR (270 MHz):
- FIG. 5;
- or a pharmaceutically acceptable salt of A54145E.
A54145F, which has the following characteristics:
- Mol. Wt.:
- 1629
- Mol. Formula:
- C.sub.71 H.sub.107 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1630.7634, Calcd. for C.sub.71 H.sub.108 N.sub.17 O.sub.27 :
- 1630.7601
- UV (EtOH) .lambda..sub.max :
- 219 nm (.epsilon. 36,750), 280 (.epsilon. 5,100), 288 (.epsilon. 4,450)
- Optical Rotation:
- [.alpha]sub.589.sup.25.degree. =-3.0.degree. (c 1.0, H.sub.2 O);
- [.alpha]sub.365.sup.25.degree. C. =-6.0.degree. (c 1.0, H.sub.2 O)
- Amino-acid Analysis:
- Asp 959(2), Thr 428(1), Glu 965(2), Gly 494(1), Ala 487(1), Val 363(1), Lys 492(1), Trp 452(1).
- .sup.1 H NMR (270 MHz):
- FIG. 6;
- or a pharmaceutically acceptable salt of A54145F.
A54145A , which has the following characteristics:
- Mol. Wt.:
- 1643
- Mol. Formula:
- C.sub.72 H.sub.109 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1644.7691, Calcd. for C.sub.72 H.sub.110 N.sub.17 O.sub.27 :
- 1644.7757
- UV (EtOH) .lambda..sub.max :
- 220 nm (.epsilon. 41,623), 281 (.epsilon. 5,750), 289 (.epsilon. 4,950)
- Optical Rotation:
- [.alpha]sub.589.sup.25.degree. C. -10.4.degree. (c 0.69, CH.sub.3 OH)
- Amino-acid analysis:
- Asp 1209(2), Thr 554(1), Glu 1209(2), Gly 636(1), Ala 617(1), Ile 576(1), Lys 604(1), Trp 514(1)
- .sup.1 H NMR (500 MHz):
- FIG. 7;
- or a pharmaceutically acceptable salt of A54145A.sub.1.
A54145B.sub.1, which has the following characteristics:
- Mol. Wt.:
- 1657
- Mol. Formula:
- C.sub.73 H.sub.111 N.sub.17 O.sub.27
- High Resolution FABMS(M+H):
- Found:
- 1658.7911, Calcd. for C.sub.73 H.sub.112 N.sub.17 O.sub.27 :
- 1658.7914
- UV (EtOH) .lambda..sub.max :
- 221 nm (e 39,100), 282 (.epsilon., 5,500), 290 (.epsilon. 4,740)
- Amino-acid Analysis:
- Asp 935(2), Thr 422(1), Glu 556(1), Gly 480(1), Ala 434(1), Ile 438(1), Lys 467(1), Trp 440(1), 3-MG 426(1);
- .sup. H 10 :H NMR (500 MHz):
- FIG. 8
- or a pharmaceutically acceptable salt of A54145B.sub.1.
Antibiotic A54145 comprising A54145A and A54145B.sub.1, which is produced by submerged aerobic fermentation of a Streptomyces fradiae strain selected from NRRL 18158, NRRL 18159 and NRRL 18160 or an A54145-producing mutant thereof.
Dependencies are inferred from the claim text.