The first synthesis of the Streptomyces derived antibiotic U-62162

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Lilian Alcaraz and Richard J. K. Taylor


Abstract

U-62162, a member of the manumycin family of antibiotics, has been prepared as a mixture of diastereoisomers and shown to contain a syn-hydroxy epoxide nucleus and a 1,3-syn-disposed dimethyl unit in the upper side chain; the cornerstone of the synthetic route utilises organometallic addition to a monoprotected quinone epoxide—the first time this approach has been successfully employed to prepare a manumycin antibiotic.


References

  1. F. Buzzetti, E. Gaumann, R. Hutter, W. Keller-Schierlein, L. Neipp, V. Prelog and H. Zaher, Pharm. Acta Helv., 1963, 38, 871 CAS; A. Zeeck, K. Schroder, K. Frobel, R. Grote and R. Thiericke, J. Antibiot., 1987, 40, 1530 CAS; A. Zeeck, K. Frobel, C. Heusel, K. Schroder and R. Thiericke, J. Antibiot., 1987, 40, 1541 CAS; We have recently completed a total synthesis of manumycin A and revised its structure to 1(L. Alcaraz, G. Macdonald, J. P. Ragot, N. J. Lewis and R. J. K. Taylor, J. Org. Chem., in the press) Search PubMed.
  2. S. Chatterjee, E. K. S. Vijayakumar, C. M. M. Franco, J. Blumbach, B. N. J. Ganguli, H. W. Fehlhaber and H. Kogler, J. Antibiot., 1993, 46, 1027 CAS; K.-I. Hayashi, M. Nakagawa, T. Fujita and M. Nakayama, Biosci. Biotechnol. Biochem., 1994, 58, 1332 CrossRef CAS.
  3. K.-I. Hayashi, M. Nakagawa and M. Nakayama, J. Antibiot., 1994, 47, 1104 CAS; K.-I. Hayashi, M. Nakagawa, T. Fujita, S. Tanimori and M. Nakayama, J. Antibiot., 1994, 47, 1110 CAS.
  4. L. Slechta, J. I. Cialdella, S. A. Mizsak and H. Hoeksema, J. Antibiot., 1982, 35, 556 CAS.
  5. L. Alcaraz, G. Macdonald, I. Kapfer, N. J. Lewis and R. J. K. Taylor, Tetrahedron Lett., 1996, 37, 6619 CrossRef CAS; R. J. K. Taylor, L. Alcaraz, I. Kapfer-Eyer, G. Macdonald, X. Wei and N. J. Lewis, Synthesis, in the press Search PubMed.
  6. E. C. L. Gautier, A. E. Graham, A. McKillop, S. P. Standen and R. J. K. Taylor, Tetrahedron Lett., 1997, 38, 1881 CrossRef CAS.
  7. C. Schregenberger and D. Seebach, Liebigs Ann. Chem., 1986, 2081 Search PubMed.
  8. J. Saunders, D. C. Tipney and P. Robins, Tetrahedron Lett., 1982, 23, 2045 CrossRef; E. A. Mash, S. B. Hemperly, K. A. Nelson, P. C. Heidt and S. Van Deusen, J. Org. Chem., 1990, 55, 2045 CrossRef CAS.
  9. Y. Hu, C. R. Melville, S. J. Gould and H. G. Floss, J. Am. Chem. Soc., 1997, 119, 4301 CrossRef CAS and references thereinfor a recent review of biosynthetic discoveries in this area, see H. G. Floss, Nat. Prod. Rep., 1997, 14, 433 Search PubMed (Section 3.4.2).
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