Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Total Synthesis of 7,9-Dideoxydaunomycinone, Aglycone of Antitumor Antibiotic Daunorubicin (Ⅰ)

항암항생제 Daunorubicin의 Aglycone, 7,9-Dideoxydaunomycinone의 합성 (제1보)

  • In Ho Cho (Department of Chemistry, Chonbuk Univeristy) ;
  • Richard P. Rhee (Department of Chemistry, Chonbuk Univeristy) ;
  • Young Soy Rho (Department of Chemistry, Chonbuk Univeristy) ;
  • F. M. Hauser (Oregon Gradeate Center)
  • 조인호 (전북대학교 자연과학대학 화학과) ;
  • 이풍래 (전북대학교 자연과학대학 화학과) ;
  • 노영쇠 (전북대학교 자연과학대학 화학과) ;
  • Published : 1986.02.20
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Abstract

7,9-Dideoxydaunomycinone (32), a late-stage precursor of the aglycone of antitumor antibiotic daunorubicin(2a) was prepared from 3-methoxybenzoic acid(5). Thus, 3-methoxybenzoic acid was converted to 4-methoxy-3-(phenylsulfonyl)-1(3H)-isobenzofuranone(11), which furnished trimethoxynaphthoate 16 upon ring annelation developed by Hauser and Rhee. The trimethoxynaphthoate 16 upon ring annelation developed by Hauser and Rbee. The trimethoxynaphtboate 16 was then transformed into phenylsulfonylnaphthofuranone 22, which was used to make anthracenoate 24 via Michael type reaction with 7-(ethylenedioxy)-2-octenoate(23). Conversion of anthracenoate 24 to tetracyclic product 28, followed by subsequent deprotection of the methyl groups in ring-B and C furnished 7, 9-Dideoxydaunomycinone(32).

항암항생제 Daunorubicin(2a)합성단계의 최종물질인 7,9-Dideoxydaunomycinone (32)를 3-methoxybenzoic acid(5)로 부터 합성하였다. 3-methoxybenzoic acid를 4-methoxy-3-(phenylsulfonyl)-1(3H)-isobenzofuranone(11)으로 변형시킨 뒤 Hauser와 Rhee가 개발한 고리접합법을 이용하여 trimethoxynaphthoate 16을 얻은 후에 phenylsulfonylnaphthofuranone 22로 변화시킨 뒤 이 물질을 7-(ethylenedioxy)-2-octenoate(23)과 Michael형태의 반응을 전개시켜 anthracenoate 24를 얻었다. Anthracenoate을 tetracyclic 화합물 28로 바꾼뒤 ring B와 C에 붙은 methyl기들을 제거하여 7,9-Dideoxydaunomycinone(32)를 만들었다.

Keywords

References

  1. J. Am. Chem. Soc. v.86 F. Arcamone;G. Franceschi;P. Orezzi;G. Cassinelli;W. Barbier;R. Mondelli
  2. Tetrahedron Lett. F. Arcamone;G. Franceschi;S. Penco;A. Selva
  3. J. Am. Chem. Soc. v.97 M. Wani;H.L. Taylor;M.E. Wall;A.T. McPhail;K.D. Onan
  4. Doxorubicin anticancer antibiotics Medicinal Chemistry v.17 F. Arcamone
  5. Autibiotics III Mechanism of Action of Antimicrobial and Antitumor Agents A. Di Marco;F. Arcamone;F. Zunino;J.M. Corcoran(Ed.);F.E. Hahn(Ed.)
  6. Cancer Chemotheraph D.W. Henry;A.C. Sartorelli(Ed.)
  7. Prog. Med. Chem. v.15 J.R. Brown
  8. Annu. Rep. Med. Chem. v.14 For an excellent comprehensive review of the literature through early 1979 see T.R. Kelly
  9. J. Am. Chem. Soc. v.102 T.R. Kelly;J. Vaya;L. Ananthasubramanian
  10. J. Org. Chem. v.46 J.S. Swenton;D.K. Anderson;L. Narashiman
  11. J. Am. Chem. Soc. v.103 F.M. Hauser;S. Prasanna
  12. J. Org. Chem. v.48 F.M. Hauser;S. Prasanna;D.W. Combs
  13. J. Chem. Soc. Perkin Trans. v.1 no.8 P.C. Bluman-Page;S.V. Ley
  14. Synth. Commun. v.14 no.5 V.H. Deshpande;K. Ravichandran;B.R. Rao
  15. JPn. Kokai Tobkyo Koho, JP59116, 246. Meiji Seiko Kasai. Ltd.
  16. J. Org. Chem. v.50 A.S. Kende;S. Johnson
  17. J. Org. Chem. v.43 F.M. Hauser;R.P. Rhee
  18. J. Org. Chem. v.29 W.H. Putterbaugh;C.R. Hauser
  19. J. Org. Chem. v.22 D.D. Wheeler;D.C. Young;D.S. Erley
  20. J. Chem. Soc. C. D.J. Brown;P.W. Ford
  21. J. Org. Chem. v.35 G.A. Russel;R.A. Ochrymowycz
  22. Thesis collection Chonbuk N. Univ. v.27 R.P. Rhee;Yonug Soy Rho
  23. J. Am. Chem. v.101 F.M. Hauser;R.P. Rhee
  24. J. Org. Chem. v.45 F.M. Hauser;R.P. Rhee
  25. J. Am. Chem. Soc. v.103 F.M. Hauser;S. Prasanna
  26. J. Org. Chem. v.44 F.M. Hauser;S. Prasanna
  27. J. Org. Chem. v.48 F.M. Hauser;S. Prasanna;D.W. Combs
  28. J. Org. Chem. v.47 F.M. Hauser;S. Prasanna
  29. J. Am. Chem. Soc. v.106 F.M. Hauser;D. Mal
  30. Org. Synth v.46 A. Kalir
  31. Tetrahedron Lett. v.14 L.I. Zakharkin;I.M. Khorlina
  32. Synthesis L. Syper;K. Kloc;J. Milochowski;Z. Szulc
  33. J. Am. Chem. Soc. v.94 C.D. Synder;H. Rapoport
  34. J. Org. Chem. v.42 M. Miyashita;A. Yoshikoshi;P.A. Grieco
  35. Tetrahedron Lett. R.C. Anderson;B. Fraser-Reid
  36. J. Am. Chem. Soc. v.89 K.H. Dahm;B.M. Trost;H. Roller
  37. J. Org. Chem. v.44 M. Imuta;H. Ziffer
  38. Topics in Antibiotic Chemistry v.2 F. Arcamone;Sammes, P. G.(ed.)
  39. J. Org. Chem. v.45 F.M. Hauser;D. W. Combs
  40. J. Am. Chem. Soc. v.105 F.M. Hauser;D. Mal
  41. J. Am. Chem. Soc. v.97 G.R. Pettit;J.J. Einck;C.L. Harald;R.H. Ode;R. Von Dreele;F. Brown;M.G. Brazhnikova;G.F. Gause
  42. J. Am. Chem. Soc. v.102 K.A. Parker;J. Kallmerten
  43. J. Org. Chem. v.103 S. D. Kimbal;D. R. Wall;F. Johnson