Stereochemical determination of thuggacins A-C, highly active antibiotics from the myxobacterium Sorangium cellulosum

Angewandte Chemie - International Edition

Volumn 47, Issue 12, 2008, Pages 2308-2311

  Bock, Martin ^a   Buntin, Kathrin ^b   Müller, Rolf ^b,c   Kirschning, Andreas ^a  

^a LEIBNIZ UNIVERSITY HANNOVER   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

Antibiotics; Gene analysis; Macrolactones; Mosher ester; Structure elucidation

Indexed keywords

CHEMICAL REACTIONS; NUCLEAR MAGNETIC RESONANCE;

GENE ANALYSIS; MACROLACTONES; MOSHER ESTER; STRUCTURE ELUCIDATION;

ANTIBIOTICS;

ANTIINFECTIVE AGENT; CARBON; GLYCOL; MACROLIDE; POLYKETIDE SYNTHASE; THUGGACIN A; THUGGACIN B; THUGGACIN C; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; ISOLATION AND PURIFICATION; METABOLISM; MYXOCOCCALES; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOISOMERISM;

ANTI-BACTERIAL AGENTS; CARBON; GLYCOLS; MACROLIDES; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MYXOCOCCALES; POLYKETIDE SYNTHASES; STEREOISOMERISM;

EID: 41049118134     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200704897     Document Type: Article

References (19)

1. J. D. McKinney, Nat. Med. 2000, 6, 1330-1333.
2. H. Steinmetz, H. Irschik, B. Kunze, H. Reichenbach, G. Höfle, R. Jansen, Chem. Eur. J. 2007, 13, 5822-5832.
3. S. Rychnovsky, D. J. Skalitzky, Tetrahedron Lett. 1990, 31, 945-948.
4. 13C) values for the quartenary C atoms are analyzed: δ ≤ 100 ppm (for 1,3-syn) and δ > 100 ppm (for 1,3-anti).
5. G. Dana, H. Denechpajouh, Bull. Soc. Chim. Fr. 1980, 395-399.
6. γ≈28 ppm; for 1,2-syn both Me≈27 ppm.
7. a) F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T. Hendrickson, W. C. Still, J. Comput. Chem. 1990, 11, 440-467;
8. b)W. C. Still, A. Tempczyk, R. C. Hawley, T. Hendrickson, J. Am. Chem. Soc. 1990, 112, 6127-6129.
9. 1H coupling constants and NOE couplings, refer to the Supporting Information.)
10. a) J. A. Dale, H. S. Mosher, J. Am. Chem. Soc. 1968, 90, 3732-3738;
11. b) J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34, 2543-2449;
12. c) J. M. Seco, E. Quinoa, R. Riguera, Chem. Rev. 2004, 104, 17-117.
13. One by-product from the formation of the S ester was assigned to be the thuggacin B derivative of diacetonide 6. The NMR data of this acetonide were in agreement with the configuration deduced from the initial acetalization studies (refer to the Supporting Information).
14. a) R. Reid, M. Piagentini, E. Rodriguez, G. Ashley, N. Viswanathan, J. Carney, D. V. Santi, C. R. Hutchinson, R. McDaniel, Biochemistry 2003, 42, 72-79;
15. b) P. Caffrey, ChemBioChem 2003, 4, 654-657.
16. a) D. Janssen, D. Albert, R. Jansen, R. Müller, M. Kalesse, Angew. Chem. 2007, 119, 4985-4988;
17. Angew. Chem. Int. Ed. 2007, 46, 4898-4901.
18. D. W. Udwary, L. Zeigler, R. N. Asolkar, V. Singan, A. Lapidus, W. Fenical, P. R. Jensen, B. S. Moore, Proc. Natl. Acad. Sci. USA 2007, 104, 10376-10381.
19. For analysis of the ketoreductase domains refer to the Supporting Information.