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Abstract

Anthracyclinones and the glycosidic anthracyclines are pigments, ranging in color from yellow to purple, which are produced by various species of Streptomyces (1, 2, 3). The very descriptive name anthracyclines was coined by Brockmann (1) and is derived from anthraquinones and the likewise tetracyclic tetracyclines. The antibiotic properties of the anthracyclines were observed soon after their discovery (for history see 4), but the compounds were far too toxic to be useful as antibiotics for treatment of infectious diseases. However, in the late sixties daunorubicin (1) was developed by Arcamone and his group at Farmitalia as well as MARAL at Rhône-Poulenc (4) into an anticancer drug especially successful in the treatment of acute leukemia. Today anthracyclines are among the most often used drugs in antitumor combination chemotherapy and the intensive research on their isolation and structure elucidation, pharmacology, biochemical mode of action as well as chemical synthesis is a result of their importance as antitumor drugs. It is therefore appropriate to demonstrate some of their structural properties on the most important members of the daunorubicin family: daunorubicin (1) and doxorubicin (2). The somewhat less cardiotoxic semisynthetic 4′-epi compounds (3) and (4) and the corresponding even more effective (but also more toxic) 4-demethoxy compounds (5) and (6) (idarubicins) obtained by chemical synthesis have also found use in clinical treatment (4, 5, 6, 7, 8).

Keywords

Building Block Total Synthesis Asymmetric Synthesis Phthalic Ester Ceric Ammonium Nitrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Brockmann, H.: Anthracycline und Anthracyclinone. Fortsch. Chem. Org. Naturst. 21, 121 Wien: Springer-Verlag. 1963.Google Scholar
  2. 2.
    Thomson, R.H.: Naturally Occurring Quinones III. London, New York: Chapman and Hall 1987.Google Scholar
  3. 3.
    Harrington, A.A., and A.D. Roberts: Dictionary of Antibiotics and Related Substances. Ed. B.W. BYCROFT, p. 30. London, New York: Chapman and Hall. 1987.Google Scholar
  4. 4.
    Arcamone, F.: Doxorubicin. New York: Academic Press. 1980.Google Scholar
  5. 5.
    Gesson, J.-P., and M. Mondon: Synthèse Totale et Activité Cytotoxique de Nouvelles Anthracyclines. Actual. Chim. Thér. 13. serte, 161.Google Scholar
  6. 6.
    Brown, J.R., and S.H. Imam: Recent Studies on Doxorubicin and its Analogues. In: Prog. Med. Chem. Eds. G.P. ELLIs and G.B. WEST, Vol. 21, pp. 170–236, 1984.Google Scholar
  7. 7.
    Anthracyclines. Current Status and New Developments. Eds. S.T. Crooke and S.D. Reich. New York: Academic Press. 1980.Google Scholar
  8. 8.
    Arcamone, F.: Properties of Antitumor Anthracyclines and New Developments in Their Application: Cain Memorial Award Lecture. Cancer Res. 45, 5995 (1985).Google Scholar
  9. 9.
    Brazhnikova, M.G., V.B. Zbaskiy, N.P. Potanova, Y.N. Scheinker, T.F. Vlasova, and B.V. Rozyngv: Antibiotiki (Moskow) 18, 1059 (1973).Google Scholar
  10. 10.
    El Khadem, H.S.: Anthracycline Antibiotics. New York, London: Academic Press. 1982Google Scholar
  11. 11.
    Kelly, T.R.: Synthetic Approaches to Anthracycline Antibiotics. Annu. Rep. Med. Chem. 14, 288 (1979).CrossRefGoogle Scholar
  12. 12.
    Broadhurst, M.J., C.H. Hassall, and G.J. Thomas: Synthesis of Anthracyclinones. Chem. and Ind. 1985, 106.Google Scholar
  13. 13.
    Krohn, K.: Total Synthesis of Anthracyclinones. Angew. Chem. 98, 788 (1986)CrossRefGoogle Scholar
  14. Krohn, K.: Angew. Chem. Int. Ed. 25, 790 (1986).Google Scholar
  15. 14a.
    Stoodley, R.J.: The Anthracycline Antibiotics: Some Synthetic Endeavours. Second SCI/RSC Medical Chemistry Symposium; Spec. Publ.-R. Chem. Soc. 1984, 134.Google Scholar
  16. 15.
    Bayer, O.: Anthrachinone. Ed. HOUBEN-WEYL-Dötz, Vol. VII/3c. Stuttgart: Thieme. 1979.Google Scholar
  17. 16.
    Arcamone, F., L. Bernardi, B. Patelli, P. Giardino, A. Dimarco, A.M. Casazza, C. Soranzo, and G. Pratesi: Synthesis and Antitumor Activity of new Daunorubicin and Adrinamycin Analogues. Experientia 34, 1255 (1978).CrossRefGoogle Scholar
  18. 17.
    Wong, C.M., D. Popien, R. Schwenk, and J. Te Raa: Synthetic Studies of Hydronaphthacenic Antibiotics. I. The Synthesis of 4-Demethoxy-7-O-methyl Daunomycinone. Can. J. Chem. 49, 2712 (1971).Google Scholar
  19. 18.
    Krohn, K., and B. Behnke: Synthetische Anthracyclinone, XV. Regio-und stereoselektive Synthese der a-, ß-und y-Rhodomycinone über intramolekulare MarschalkCyclisierung. Chem. Ber. 113, 2994 (1980).CrossRefGoogle Scholar
  20. 19.
    Matsumoto, T., M. Ohsaki, M. Suzuki, Y. Kimura, and S. Terashima: Synthesis of 4-Demethoxyanthracyclines Carrying a Lipophilic Alkanoyl Group at the C9-Position. Chem. Pharm. Bull. 34, 4605 (1986).CrossRefGoogle Scholar
  21. 20.
    Confalone, P.N., and G. Pizzglato: Total stereospecific Synthesis of (±)-Aklavinone. J. Am. Chem. Soc. 103, 4251 (1981).CrossRefGoogle Scholar
  22. 21.
    Gleim, R.D., S. Trenbeath, F. Suzuki, and C.J. Sin: Regiospecific Syntheses of Islandicin and Digitopurpone Monomethyl Ethers. J. Chem. Soc., Chem. Commun. 1978, 242.Google Scholar
  23. 22.
    Broadhurst, M.J., and C.H. Hassall: Anthracyclines. Part 1. The Synthesis of Racemic Daunomycinone and Some related Tetrahydronaphthacenequinones. J. Chem. Soc. Perkin Trans. 1 1982, 2227.Google Scholar
  24. 23.
    Braun, M.: Regioselektive Synthese von Daunomycinon und y-Rhodomycinon. Tetrahedron Lett. 21, 3871 (1980).CrossRefGoogle Scholar
  25. 24.
    Braun, M.: A Regioselective Synthesis of Daunomycinone and Related Anthracyclinones. Tetrahedron 40, 4585 (1984).CrossRefGoogle Scholar
  26. 25.
    Braun, M., R. Veith, and G. Moll: Regioselektive Addition von Grignard-Reagentien an 3-Methoxy-und 3-Nitrophthalsäureanhydride. Chem. Ber. 118, 1058 (1985).CrossRefGoogle Scholar
  27. 26.
    Parker, K.A., and J. Kallmerten: Efficient, Regiospecific Synthesis of Anthracyc-line Intermediates: Total Synthesis of Daunomycinone. J. Am. Chem. Soc. 102, 5881 (1980).CrossRefGoogle Scholar
  28. 27.
    Parker, K.A., and J. Kallmerten: Approaches to Anthracyclines. 1. Conjugate Aroylation of a,I3-Unsaturated Esters. J. Org. Chem. 45, 2614 (1980).CrossRefGoogle Scholar
  29. 28.
    Parker, K.A., and J. Kallmerten: Approaches to Anthracyclines. 2. Regiospecific Annelative Quinone Synthesis. J. Org. Chem. 45, 2620 (1980).CrossRefGoogle Scholar
  30. 29.
    Tanno, N., and S. Terashima: Asymmetric Synthesis of Optically Active Anthracyclinone Intermediates and 4-Demethoxyanthracyclinones by the Use of a Novel Chiral Reducing Agent. Chem. Pharm. Bull. 31, 821 (1983).CrossRefGoogle Scholar
  31. 30.
    Russell, R.A., R.W. Irvine, and A.S. Krauss: A Caveat Regarding Chiroptical Measurements of Chiral Anthracyclinones. Tetrahedron Lett. 25, 5817 (1984).CrossRefGoogle Scholar
  32. 31.
    Welzel, P.: Asymmetrische Diels Alder Reaktionen. Nachr. Chem. Tech. Lab. 31, 979 (1983).CrossRefGoogle Scholar
  33. 32.
    Krohn, K.: Asymmetrische Induktion bei Diels-Alder Reaktionen. Nachr. Chem. Tech. Lab. 35, 836 (1987)CrossRefGoogle Scholar
  34. 33.
    Tamirez, J., and P. Vogel: Macrocycles by Intramolecular Diels-Alder Reaction — Regioselective Synthesis of Anthracycline Precursors. Angew. Chem. 96, 61 (1984)CrossRefGoogle Scholar
  35. Tamirez, J., and P. Vogel: Angew. Chem. Int. Ed. 23, 74 (1984).Google Scholar
  36. 34.
    Breslow, R., R.J. Corcoran, B.B. Snider, R.J. Coll, P.L. Khanna, and R. Kaleya: Selective Halogenation of Steroids Using Attached Aryl Iodide Templates. J. Am. Chem. Soc. 99, 905 (1977).CrossRefGoogle Scholar
  37. 35.
    Kelly, R.T., L. Ananthasubramanian, K. Borah, J.W. Gillard, R.N. Goerner JR., P.F. King, J.M. Lyding, W.-G. Tsang, and J. Vaya: An Efficient Regioselective Synthesis of (±)-Daunomycinone. Tetrahedron 40, 4569 (1984).CrossRefGoogle Scholar
  38. 36.
    Echavarren, A., P. Prados, and F. Farina: Polycyclic Hydroxyquinones-XIX. Regiospecific Synthesis of Anthracyclinones via the Diels-Alder Reaction with Dichloronaphthazarins. Tetrahedron 40, 4561 (1984).CrossRefGoogle Scholar
  39. 37.
    Potman, R.P., N.J.M.L. Janssen, J.W. Scheeren, and R.J.F. Nivard: Application of 1-tert.-Butoxy-3-[(trimethylsil)oxylbuta-1,3-diene in the Preparation of Functionalized ß-Hydroxycyclohexanone Derivatives, Including Valuable Precursors of Daunomycinone Analogues. J. Org. Chem. 52, 3628 (1984).CrossRefGoogle Scholar
  40. 38.
    Krohn, K., and K. Tolkiehn: Stereoselektive Synthese des 4-Desmethoxydaunomycinons. Tetrahedron Lett. 1978, 4023.Google Scholar
  41. 39.
    Krohn, K.: Synthetische Anthracyclinone, XVI. Synthese hydroxylierter Anthra-chinone durch regioselektive Diels-Alder Reaktion. Tetrahedron Lett. 21, 3557 (1980)Google Scholar
  42. Krohn, K.: Synthetische Anthracyclinone, XVI. Synthese hydroxylierter Anthra-chinone durch regioselektive Diels-Alder Reaktion. Tetrahedron Lett. 21, 3557 (1980).Google Scholar
  43. 40.
    Krohn, K.: Synthetische Anthracyclinone, XXIII. Synthese and Konfiguration der stereoisomeren Aklavinone. Liebigs Ann. Chem. 1983, 2151.Google Scholar
  44. 41.
    Kelly, T.R., N.D. Parekh, and E.N. Trachtenberg: Regiochemical Control in the Diels-Alder Reaction of Substituted Naphthoquinones. The Directing Effects of C-6 Oxygen Substituents. J. Org. Chem. 47, 5009 (1982).CrossRefGoogle Scholar
  45. 42.
    Boeckman, R.K., JR., T.M. Dolak, and K.O. Culos: Diels-Alder Cycloaddition of Juylone Derivatives: Elucidation of Factors Influencing Regiochemical Control. J. Am. Chem. Soc. 100, 7098 (1978).Google Scholar
  46. 43.
    Rozeboom, M.D., L.-M. Tegmo-Larsson, and K. N. Houx: J. Org. Chem. 46, 2338 (1981).CrossRefGoogle Scholar
  47. 44.
    Savard, J., and P. BRASSARD: Regiospecific Syntheses of Quinones using Vinylketene Acetals Derived from Unsaturated Esters. Tetrahedron Lett. 1979, 4911.Google Scholar
  48. 45.
    Pearlman, B.A., J.M. Mcnamara, I. Hasan, S. Hatakeyama, H. Sekizaki, and Y. Klan: Practical Total Synthesis of (±)-Aklavinone and Total Synthesis of Aklavin. J. Am. Chem. Soc. 103, 4248 (1981).CrossRefGoogle Scholar
  49. 46.
    Gesson, J.P., J.C. Jacquesy, and B. Renoux: Approach to the Synthesis of Steffimy-cines; Preparation and Antibacterial Activity of (+)-8-Demethoxy-7-epi (?) Steffimycinone. Tetrahedron Lett. 24, 2761 (1983).CrossRefGoogle Scholar
  50. 47.
    Marschalk, C., F. Koenig, and N. Ouroussoff: Nouvelle méthode d’introduction des chaines latérales dans le noyau anthraquinoique. Bull. Soc. Chim. F. 3, 1545 (1936).Google Scholar
  51. 48.
    Krohn, K., and C. Hemme: Synthetische Anthracyclinone, VI. Synthese strukturanaloger Anthracyclinone. Liebigs Ann. Chem. 1979, 35.Google Scholar
  52. 49.
    Krohn, K., and C. Hemme: Synthetische Anthracyclinone, V. Alkylierung von Anthrachinonen als variabler Syntheseweg zu Anthracyclinon-Vorstufen. Liebigs Ann. Chem. 1979, 19.Google Scholar
  53. 50.
    Krohn, K., and B. Behnke: Synthetische Anthracyclinone XXII. Rhodomycinone vom Typ A mit Methyl-, Ethyl-und n-Propylseitenkette. Liebigs Ann. Chem. 1983, 1818.Google Scholar
  54. 51.
    Harwood, L.M., L.C. Hodgkinson, and J.K. Sutherland: Regioselective Synthesis of 2- and 3-Alkyl-5-hydroxyquinizarins. J. Chem. Soc., Chem. Commun. 1978, 712.Google Scholar
  55. 52.
    Mincher, D.J., and G. Shaw: Anthracyclinones. Part. 2. The Use of 1,2.:5,6-Di-Oisopropylidene-a-D-glucofuranose as achiral Template Precursor in an Anthracyclinone Synthesis. J. Chem. Soc. Perkin 1 1984, 1279.Google Scholar
  56. 53.
    Florent, J.C., J. Ughetto-Monfrin, and C. Monneret: Anthracyclinones. 2. Isosaccharinic Acid as Chiral Template for the Synthesis of (+)-4-Demethoxy-9deacetyl-9-(hydroxymethyl)daunomycinone and (—)-4-Deoxy-y-rhodomycinone. J. Org. Chem. 52, 1051 (1987).Google Scholar
  57. 54.
    Krohn, K., E. Broser, and H. Heins: Chiral Building Blocks from Methyl a-DMannopyranoside and Methyl a-D-Glucopyranoside for Anthracyclinone Synthesis. Carbhydr. Res. 164, 59 (1987).CrossRefGoogle Scholar
  58. 55.
    Krohn, K., and U. Müller: Synthesis of 4-Demethoxyrhodomycinones with Incorporation of (S)-Lactic Acid. Tetrahedron 42, 6635 (1986).CrossRefGoogle Scholar
  59. 56.
    Krohn, K., and I. Hamann: Anthracyclinones 37. Total Synthesis of (+)- I-Rhodomycinon. Liebigs Ann. Chem. 1988, 949.Google Scholar
  60. 57.
    Boddy, I.K., P.J. Boniface, R.C. Cambie, P.A. Craw, Z.-D. Huang, D.S. Larsen, H. Mcdonald, P.S. Rutledge, and P.D. Woodgate: Experiments Directed Towards the Synthesis of Anthracyclinones. VIII; Functionalization of Hydroxyanthraquinones by Reductive Claisen Rearrangement. Aust. J. Chem. 37, 1511 (1984).CrossRefGoogle Scholar
  61. 58.
    Davies, D.T., P.S. Jones, and J.K. Sutherland: A Second Synthesis of 7,9-Bisdideoxycarminomycinone from 5-Hydroxyquinizarin Tetrahedron Lett. 24, 519 (1983).Google Scholar
  62. 59.
    Ashcroft, A.E., D.T. Davies, and J.K. Sutherland: The Synthesis of Anthracyclinones-II. The Synthesis of 7,9-Bisdeoxycarminomycinone and -Daunomycinone. Tetrahedron 40, 4579 (1984).CrossRefGoogle Scholar
  63. 60.
    Krohn, K., and M. Radeloff: Stereoselektive Totalsynthese von Anthracyclinonen. Chem. Ber. 111, 3823 (1978).CrossRefGoogle Scholar
  64. 61.
    Krohn, K.: Synthetische Anthracyclinone XIX. Totalsynthese des und a-Rhodomycinons. Tetrahedron Lett. 22, 3219 (1981).CrossRefGoogle Scholar
  65. 62.
    Boeckman, R.K., JR., and F.-W. Sum: An Efficient Total Synthesis of (±)-Aklavinone. J. Amer. Chem. Soc. 104, 1604 (1982).Google Scholar
  66. 63.
    Hauser, F.M., and D. Mal: Regiospecific Total Synthesis of (+)-Aklavinone and (+)-Pyrromycinone from a Common Synthon. J. Am. Chem. Soc. 106, 1098 (1984).CrossRefGoogle Scholar
  67. 64.
    Hauser, F.M., and S. Prasanna: A General Route for Total Synthesis of 9-Alkyl-9Hydroxy Aklavinones and Pyrromycinones. Tetrahedron 40, 4711 (1984).CrossRefGoogle Scholar
  68. 65.
    Krohn, K., and H.-J. Kohle: Synthetic Anthracyclinones, 35. Synthese des Nogalamycinon-Aglycons. Liebigs Ann. Chem. 1987, 1037.Google Scholar
  69. 66.
    Krohn, K., and W. Priyono: Synthetic Anthracyclinones, XXXI. Total Synthesis of Racemic c-Rhodomycinones via Keto-Ester Cyclization. Liebigs Ann. Chem. 1986, 1506.Google Scholar
  70. 67.
    Kende, A.S., and S.D. Boettger: Regiospecific Total Synthesis of (+)-11-Deoxycarminomycinone. J. Org. Chem. 46, 2799 (1981).CrossRefGoogle Scholar
  71. 68.
    Kende, A.S., and J.P. Rizzi: A Stereospecific Total Synthesis of Aklavinone. J. Am. Chem. Soc. 103, 4247 (1981).CrossRefGoogle Scholar
  72. 69.
    Hauser, F.M., and S. Prasadena: Synthetic Studies on Anthracyclines. J. Org. Chem. 44, 2596 (1979).CrossRefGoogle Scholar
  73. 70.
    Hauser, F.M., and S. Prasadena: Total Synthesis of (+)-Daunomycinone. Regiospecific Preparations of (+)-7,9Dideoxydaunomycinone and 6,11-Dihydroxy-4-methoxy-7,8,9,10-tetrahydronaphthacene-5,9,12-trione. J. Am. Chem. Soc. 103, 6378 (1981).CrossRefGoogle Scholar
  74. 71.
    Russell, R., R.W. Irvine, and R.N. Warrener: The Total Synthesis of Optically Pure (9R, 13S)- and (9R, 13R)-7-Deoxy-13-dihydrodaunomycinone. J. Org. Chem. 51, 1595 (1986).CrossRefGoogle Scholar
  75. 72.
    Russell, R.A., and R.N. Warrener: The Regiospecific Preparation of 1,4-Dioxygenated Anthraquinones: a New Route to Islandicin, Digitopurpone, and Madeirin. J. Chem. Soc., Chem. Commun. 1981, 108.Google Scholar
  76. 73.
    Swenton, J.S., J.N. Frescos, G.W. Morrow, and A.D. Sercel: A Convergent Synthesis of (+)-4-Demethoxydaunomycinone and (+)-Daunomycinone. Tetrahedron 40, 4625 (1984).CrossRefGoogle Scholar
  77. 74.
    Kündig, E.P., V. Desorby, and D.P. Simmons: Regioselectivity in the Addition of Carbanions to (1,4-Dimethoxynaphthalene)tricarbonylchromium. A New Entry into Anthracyclinone Synthesis. J. Am. Chem. Soc. 105, 6962 (1983).Google Scholar
  78. 75.
    Dötz, K.H., and M. Popall: Carbene Ligands as Anthracyclinone-Synthons II; Chromium Mediated Cycloaddition of Alkenes, Carbenes and Carbon Monoxide: Application to Ring B Synthesis in Anthacyclinones. Tetrahedron 41, 5797 (1985).CrossRefGoogle Scholar
  79. 76.
    Dötz, K.H., M. Popall, and G. Müller: Metal Carbene Chelates; Stable Reactive Intermediates in Cycloaddition Reactions. J. Organomet. Chem. 291, Cl (1985).Google Scholar
  80. 77.
    Dötz, K.H., M. Popall, G. Dötz, and K. Ackermann: Carbenkomplexe mit Chinonbisketal-Funktionen. Angew. Chem. 98, 909 (1986)CrossRefGoogle Scholar
  81. Dötz, K.H., M. Popall, G. Dötz, and K. Ackermann: Angew. Chem. Int. Ed. Engl. 25, 911 (1986).Google Scholar
  82. 78.
    Dötz, K.H., and M. Popall: Anthrachinon-Ring-C-Synthese via Chelat-Carbenkomplexe. Angew. Chem. 99, 1220 (1987)CrossRefGoogle Scholar
  83. Dötz, K.H., and M. Popall: Angew. Chem. Int. Ed. 26, 1158 (1987).Google Scholar
  84. 79.
    Wulff, W.D., and P.-C. Tang: Anthracycline Synthesis with Fischer Carbene Complexes. J. Am. Chem. Soc. 106, 434 (1984).CrossRefGoogle Scholar
  85. 80.
    Wulff, W.D., P.-C. Tang, K.-S. Chan, J.S. Mccallum, D.C. Yang, and S.R. Gilbertson: Cycloadditions and Annulations of Transition Metal Carbene Complexes. Tetrahedron 41, 5813 (1985).CrossRefGoogle Scholar
  86. 81.
    Semmelhack, A.: Ring EDC-Nogalamycinon-Building Block. Personal communication.Google Scholar
  87. 82.
    Wong, C.-M., H.-Y. Lam, W. Haque, A.-Q. Mi, and G.-S. YANG: A Practical Synthesis of an Anthracyclinone Synthon. Can. J. Chem. 51, 562 (1983).CrossRefGoogle Scholar
  88. 83.
    Wong, C.-M., A.-Q. Mi, J. Ren, W. Haque, and K. Marat: Heteroanthracylines-III. 6,7,11-Tri-O-methyl-4-demethoxy-12-sulfonodaunomycinone [6,10,11-Trimethoxy-8-hydroxy-8-acetyl-7,8,9,10-tetrahydrobenzo(B)-thioxanthen-12-one-5-dioxide]. Tetrahedron 40, 4789 (1984).CrossRefGoogle Scholar
  89. 84.
    Rao, A.V.R., B. Chandra, and H.B. Borate: A Convenient Approach to the Total Synthesis of (±)-4-Demethoxydaunomycinone. Tetrahedron 38, 3555 (1982).CrossRefGoogle Scholar
  90. 85.
    Regiospecific Synthesis of (+)-7,9-Dideoxydaunomycinone. Indian. J. Chem. 22B, 521 (1983).Google Scholar
  91. 86.
    Rao, A.V.R., A.R. Mehendale, and K.R. Reddy: An Efficient and Flexible Approach for the Synthesis of 4-Demethoxydaunomycinone and 4-Demethoxy-11deoxydaunomycinone. Tetrahedron Lett. 24, 1093 (1983).CrossRefGoogle Scholar
  92. 87.
    Genot, A., J.-C. Florent, and C. Monneret: Anthracyclinones. 3. Chiral Pool Synthesis of Anthracyclinones via Tetralin Intermediates. J. Org. Chem. 52, 1057 (1987).CrossRefGoogle Scholar
  93. 88.
    Krohn, K., and H. Rieger: Synthetische Anthracyclinone XXXIV. Ein enantiomerenreiner AB-Baustein zur Daunomycinon-Synthese unter Einbau von (S)-Äpfelsäure. Liebigs Ann. Chem. 1987, 517.Google Scholar
  94. 89.
    Seebach, D., R. Naef, and G. Calderari: a-Alkylation of a-Heterosubstituted Carboxylic Acids Without Racemization. Tetrahedron 40, 1313 (1984).CrossRefGoogle Scholar
  95. 90.
    Corey, E.J., and M. Chaykovsky: Methylsulfinyl Carbanion (CH3-SO-CH,-). Formation and its Application to Organic Synthesis. J. Am. Chem. Soc. 87, 1345 (1965).CrossRefGoogle Scholar
  96. 91.
    Broadhurst, M., C.H. Hassall, and G.J. Thomas: Anthracyclines. Part 2. Investigations relating to the Synthesis of 4-Demethoxyanthracyclinones. J. Chem. Soc. Perkin Trans. 1 1982, 2239.Google Scholar
  97. 92.
    Krohn, K., H. Rieger, E. Broser, P. Schiess, S. Chen, and T. Strubin: Synthese symmetrisch substituierter Daunomycinon-Derivate. Liebigs. Ann. Chem. 1988, 943.Google Scholar
  98. 93.
    Wong, C.M., R. Schwenk, D. Popein, and T. Ho: The Total Synthesis of Daunomycinone. Can. J. Chem. 51, 466 (1973).CrossRefGoogle Scholar
  99. 94.
    Lown, J.W., S.M. Sondhi, S.B. Mandal, and J. Murphy: Synthesis and Redox Properties of Chromophore Modified Glycosides Related to Anthracyclines. J. Org. Chem. 47, 4304 (1982).Google Scholar
  100. 95.
    Tracy, M., and E.M. Acton: Synthesis of Tetrahydrobenzo{b}phenazines as Anthracyclinone N-Isosters. J. Org. Chem. 49, 5116 (1984).CrossRefGoogle Scholar
  101. 96.
    Broadhurst, M.J., C.H. Hassall, and G.J. Thomas: Total Synthesis of 4-Demethoxydaunomycinone. J. Chem. Soc., Chem. Commun. 1982, 158.Google Scholar
  102. 97.
    Chenard, B.L., M.G. Dolson, A.D. Sercel, and J.S. Swenton: Annelation Reactions of Quinone Monoketals. Studies Directed at an Efficient Synthesis of Anthracyclinones. J. Org. Chem. 49, 318 (1984).Google Scholar
  103. 98.
    Swenton, J.S., F.K. Anderson, D.K. Jackson, and L.Narasimhan: 1,4-DipoleMetalated Quinone Stratergy to (±)-4-Demethoxydaunomycinone and (±)-Dauno-mycinone. Annelation of Benzocyclobutenedione Monoacetals with Lithioquinone Bisketals. J. Org. Chem. 46, 4825 (1981).CrossRefGoogle Scholar
  104. 99.
    Gardner, J.N., F.E. Carbon, and D. Gnoj: A One-Step Procedure for the Preparation of Tertiary a-Ketols from the Corresponding Ketones. J. Org. Chem. 33, 3294 (1968).CrossRefGoogle Scholar
  105. 100.
    Del Nero, S., C. Gandolfi, P. Lombardi, and F. Arcamone: Preparation of (—)1,4-Dimethoxy-6-acetyl-6-hydroxytetralin: Intermediate for Anthracyclinones Synthesis. Chem. Ind. ( London ) 1981, 810.Google Scholar
  106. 101.
    Broadhurst, M.J., C.H. Hassall, and G.J. Thomas: Anthracyclines. Part 3. The Total Synthesis of 4-Demethoxydaunomycin. J. Chem. Soc. Perkin Trans. 1 1982, 2249.Google Scholar
  107. 102.
    Broadhurst, M.J., C.H. Hassall, and G.J. Thomas: Total Synthesis of some new 4-Demethoxyanthracyclinones. Tetrahedron 40, 4649 (1984).CrossRefGoogle Scholar
  108. 103.
    Jew, S., S. Terashima, and K. Koga: Asymmetric Halolactonization Reactions. 3. Asymmetric Synthesis of Optically Active Anthracyclinones. Chem. Pharm. Bull. 27, 2351 (1979).CrossRefGoogle Scholar
  109. 104.
    Russell, R.A., P.S. Gee, R.W. Irvine, and R.N. Warrener: Anthracyclines. X. The Enantiospecific Synthesis of (—)-(7R)-7-Acetyl-7-hydroxy-4,4-dimethoxy5,6,7,8-tetrahydronaphthalen-1(4H)-one; a Type I Chiral Dienone for the Synthesis of 7-Deoxydaunomycinone. Aust. J. Chem. 37, 1709 (1984).Google Scholar
  110. 105.
    Tomioka, K., M. Nakajima, and K. Kola: Enantioface Differentiation in Cis Dihydroxylation of C-C Double Bonds by Osmium Tetroxide with Use of a Chiral Diamine with DZ Symmetry. J. Am. Chem. Soc. 109, 6213 (1987).CrossRefGoogle Scholar
  111. 106.
    Moore, J.A., and M. Rahm: The Synthesis of 6-Hydroxy-1,3,4,5-tetrahydrobenz[cd]indole. J. Org. Chem. 26, 1109 (1961).Google Scholar
  112. 107.
    Watanabe, M., H. Maenosono, and S. Furukawa: A Regiospecific Synthesis of Anthracyclinones Using directed Metalation. Chem. Pharm. Bull. 31, 2662 (1983).CrossRefGoogle Scholar
  113. 108.
    Blade, R.J., and P. Hodge: Synthetic Routes to (+)-Daunomycinone: Elaboration of the Hydroxy-ketone Group from an a-Tetralone Derivative, and Selective Methylation of C(4)-Hydroxy Group Using Diazomethane. J. Chem. Soc., Chem. Commun. 1979, 85.Google Scholar
  114. 109.
    Freskos, J.N., G.W. Morrow, and J.S. Swenton: Synthesis of Functionalized Hydroxyphthalides and Their Conversion to 3-Cyano-1(3H)-isobenzofuranones. The Diels-Alder Reaction of Methyl 4,4-Diethoxybutynoate and Cyclohexadienes. J. Org. Chem. 50, 805 (1985).CrossRefGoogle Scholar
  115. 110.
    Russell, R.A., G.J. Collin, M.P. Crane, P.S. Gee, A.S. Krauss, and R.N. Warrener: Anthracyclines. XI. A Short, Site-Specific Synthesis of Unsymmetrical 3Acetyl-5,8-dialkoxy-1,2-dihydronaphthalenes; Key Precursors to Daunomycinone AB-Synthons. Aust. J. Chem. 37, 1721 (1984).CrossRefGoogle Scholar
  116. 111.
    Reddy, M.P., and G.S.K. Rao: A High Yield Synthesis of (±)-5,8-Dimethoxy-2-a.hydroxymethyl-3,4-dihydronaphthalene, a Key Intermediate in Anthracyclinone Synthesis. Tetrahedron Lett. 22, 3549 (1981).CrossRefGoogle Scholar
  117. 112.
    Rao, A.V.R., J.S. Yadav, K.B. Reddy, and A.R. Mehendale: A Stereoconvergent Synthesis of (+)-4-Demethoxydaunomycinone. J. Chem. Soc., Chem. Commun. 1984, 453.Google Scholar
  118. 113.
    Rao, A.V.R., J.S. Yadav, K.B. Reddy, and A.R. Mehendale: A Stereoconvergent Synthesis of (+)-4-Demethoxydaunomycinone. Tetrahedron 40, 4643 (1984).CrossRefGoogle Scholar
  119. 114.
    Rao, A.V.R., B.M. Chandra, and H.B. Borate: A General Method for the Synthesis of 11-Deoxyanthracyclinones. Synth. Commun. 14, 257 (1984).CrossRefGoogle Scholar
  120. 115.
    Rao, A.V.R., K.B. Reddy, and A.R. Mehendale: A Regiospecific and Flexible Approach for the Synthesis of (+)-Daunomycinone and (+)-11-Deoxydaunomycinone. J. Chem. Soc., Chem. Commun. 1983, 564.Google Scholar
  121. 116.
    Rao, A.V.R., V.H. Deshpande, and N.L. Reddy: A Short Synthesis of (±)-2-Acetyl5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol — A Key Intermediate for Anthracyclinone Synthesis. Tetrahedron Lett. 23, 4373 (1982).CrossRefGoogle Scholar
  122. 117.
    Cambie, R.C., T.A. Howe, M.G. Paullser, P.S. Rutledge, and P.D. Woodgate: Experiments directed towards the Synthesis of Anthracyclinones. XIV. An Intermediate for the Synthesis of Vineomycins. Aust. J. Chem. 40, 1063 (1987).CrossRefGoogle Scholar
  123. 118.
    Cambie, R.C., D.S. Larsen, P.S. Rutledge, and P.D. Woodgate: Experiments Directed Towards the Synthesis of Anthracyclinones. XIII. Ozonolysis of Anthrafurans. Aust. J. Chem. 40, 215 (1987).CrossRefGoogle Scholar
  124. 119.
    Coburn, C.E., D.K. Anderson, and J.S. Swenton: Convenient AB-Ring Segments for Anthracyclinone Synthesis via Bishydroxylation of 2-Ethyl-5,8-dimethoxy-7-bromo-1-tetralone. J. Org. Chem. 48, 1455 (1983).CrossRefGoogle Scholar
  125. 120.
    Swenton, J.S., D.K. Anderson, C.E. Coburn, and A.P. Haag: The Synthesis of 6-Demethoxyanthracyclinones: (+)-Citromycinone and (+)-Demethoxy-deoxydaunomycinone. Tetrahedron 40, 4633 (1984).CrossRefGoogle Scholar
  126. 121.
    Li, T.-T., Y.L. Wu, and T.C. Walsgrove: A Facile Total Synthesis of Racemic Aklavinone. Tetrahedron 40, 4701 (1984).CrossRefGoogle Scholar
  127. 122.
    Hauser, F.M., and D. Mal: Total Synthesis of 11-Deoxydaunomycinone. J. Am. Chem. Soc 105, 5688 (1983).CrossRefGoogle Scholar
  128. 123.
    Rao, A.V.R., V.H. Deshpande, and N.L. Reddy: A Simple Synthesis of (±)-4Demethoxydaunomycinone. Tetrahedron Lett. 21, 2661 (1980).CrossRefGoogle Scholar
  129. 124.
    Kende, A.S., D.P. Curran, Y. Tsay, and J.E. Mills: The Isobenzofurane Route to Anthracyclinones. Tetrahedron Lett. 1977, 3537.Google Scholar
  130. 125.
    Umezawa, H., Y. Takahashi, M. Kinoshita, H. Naganawa, K. Tatsuta, and T. Takeuchi: Synthesis of 4-Demethoxy-11-deoxy-analogs of Daunomycin and Adriamycin. J. Antibiotics 33, 1581 (1980).Google Scholar
  131. 126.
    Deshpande, V.H., K. Ravichandran, and B.R. Rao: Synthesis of (±)-4-Demethoxy-7,11-dideoxydaunomycinone. Synth. Commun. 14, 477 (1984).CrossRefGoogle Scholar
  132. 127.
    Smith, T.H., A.N. Fujiwara, W.W. Lee, H.Y. Wu, and D.W. Henry: Synthetic Approaches to Adriamycin. 2. Degradation of Daunorubicin to a Nonasymmetric Tetracyclic Ketone and Refunctionalization to the A Ring to Adriamycin. J. Org. Chem. 42, 3653 (1977).CrossRefGoogle Scholar
  133. 128.
    Alexander, J., I. Khanna, D. Lednicer, L.A. Mitscher, T. Veysoglu, Z. Wielogorski, and R.L. Wolgemuth: Total Chemical Synthesis and Antitumor Evaluation of 4-Demethoxy-10,10-dimethyldaunomycinone. J. Med. Chem. 27, 1343 (1984).CrossRefGoogle Scholar
  134. 129.
    Wiseman, J.R., N.I. French, R.K. Hallmark, and K.G. Chiong: The ortho-Quinodimethane Route to Anthracyclinones. A New Synthesis of 4-Demethoxydaunomycinone. Tetrahedron Lett. 1978, 3765.Google Scholar
  135. 130.
    Preston, P.N., T. Winwick, and J.O. Morley: Selective Demethylation of Di-and Trimethoxyanthraquinones via Aryloxydifluoroboron chelates. Synthesis of 4Hydroxy-1,5-dimethoxyanthraquinone and 1,4-Dihydroxy-5-methoxyanthraquinone. J. Chem. Soc., Chem. Commun. 1983, 89.Google Scholar
  136. 131.
    Suzuki, M., Y. Kimura, and S. Terashima: A Novel Synthesis of the a-Hydroxyketone Moiety of Anthracyclinones by the Use of 2-Trimethylsilylethynylcerium(III) Reagents. Chem. Lett. 1984, 1543.Google Scholar
  137. 132.
    Tamura, Y., M. Sasho, H. Ohe, S. Akai, and Y. Kim: A Short and Efficient Synthesis of 11-Deoxyanthracyclinones: Strong Base-Induced Cycloaddition of the Suitably Substituted Tetrahydrohomophthalic Anhydride. Tetrahedron Lett. 26, 1549 (1985).CrossRefGoogle Scholar
  138. 133.
    Suzuxr, M., Y. Kimura, and S. Terashima: Novel Ethynylcerium(III) Reagents as Effective Tools for Constructing the a-Hydroxy Methyl Ketone Moiety of Anthracyclinones. Chem. Pharm. Bull. 34, 1531 (1986).CrossRefGoogle Scholar
  139. 134.
    Tamura, Y., M. Sasho, S. Akai, and H. Kishimoto: A Highly Convergent Strategy for the Synthesis of 4-Demethoxydaunomycinone and Daunomycinone: A Novel Synthesis of C4-Acetoxylated Homophthalic Anhydrides. Tetrahedron Lett. 27, 195 (1986).CrossRefGoogle Scholar
  140. 135.
    Tamura, Y., S. Akai, H. Kishimoto, M. Kirihara, M. Sasho, and Y. Kita: Practi-cal Total Synthesis of 11-Deoxydaunomycinone and the First Total Synthesis of 11-Deoxydaunomycin. Tetrahedron Lett. 28, 4583 (1987).CrossRefGoogle Scholar
  141. 136.
    Sodeoka, M., T. Irmori, and M. Shibassaki: Stereospecific Synthesis of exo-Allylic Alcohol. An Efficient Asymmetric Synthesis of (R)-(—)-2-Acetyl-5,8-dimethoxy1,2,3,4-tetrahydro-2-naphthol. Tetrahedron Lett. 26, 6497 (1985).Google Scholar
  142. 137.
    Hiyama, T., M. Sawahata, and Y. Kusano: Manganese-Mediated Allyl Addition to Enolizable Aldehyde and Ketones. An Approach for Introduction of Acetonyl Side Chains at C(9) of Anthracycline Antibiotics. Chem. Lett. 1985, 611.Google Scholar
  143. 138.
    Isizumi, K., N. Oiiashi, and N. Tanno: Stereospecific Total Synthesis of 9-Aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and Related Compounds. J. Org. Chem. 52, 4477 (1987).Google Scholar
  144. 139.
    Tamura, Y., H. Annoura, H. Yamamoto, H. Kondo, Y. Kita, and H. Fujioka: Asymmetric Synthesis of Anthracyclinones Using Chiral Acetal: Synthesis of a new Chiral AB-Synthon, (—)-2-Bromo-6-ethynyl-6-hydroxy-5,6,7,8-tetrahydro-1,4naphthoquinone, and its Application for (—)-7-Deoxydaunomycinone. Tetrahedron Lett. 28, 5709 (1987).CrossRefGoogle Scholar
  145. 140.
    Ardecky, R.J., D. Dominguez, and M.P. Cava: 3-(Acyloxy)-3-buten-2-ones as Dienophiles in Anthracyclinone Synthesis. An Efficient Route to 4-Demethoxy-7deoxydaunomycinone Derivatives. J. Org. Chem. 47, 409 (1982).CrossRefGoogle Scholar
  146. 141.
    Stephan, D., A. Gorgues, and A. Leco: Reduction D’a,a-Dibromoorthoxylenes par les sels Chromeux: Génération Facile D’Orthoquinodimethanes. Tetradedron Lett. 25, 5649 (1984).CrossRefGoogle Scholar
  147. 142.
    Ardecky, R.J., F.A.J. Kerdesky, and M.P. Cava: Dienophilic Reactions of 3[(Trimethylsilyl)oxy]-3-buten-2-one. J. Org. Chem. 46, 1483 (1981).CrossRefGoogle Scholar
  148. 143.
    Honek, J.F., M.L. Mancini, and B. Belleau: New Strategy for the Synthesis of Key Anthracycline Precursors. Tetrahedron Lett. 24, 257 (1983).CrossRefGoogle Scholar
  149. 144.
    Krohn, K.: Synthetische Anthracyclinone, XVIII. Synthese des 13-Desoxo-6desoxydaunomycinons und des 11-Citromycinons. Liebigs Ann. Chem. 1981, 2285.Google Scholar
  150. 145.
    Kerdesky, F.A.J., R.J. Ardecky, M.V. Lakshmikantham, and M.P. Cava: Simple o-Quinodimethane Route to (+)-4-Demethoxydaunomycinone. J. Am. Chem. Soc. 103, 1992 (1981).Google Scholar
  151. 146.
    Watabe, T., Y. Takahashi, and M. Oda: 1,2-Dihydro-3,10-dihydroxycyclobut[b]anthracene-4,9-dione; a Key Intermediate for 4-Demethoxyanthracyclinones. Tetrahedron Lett. 24, 56 (1983).CrossRefGoogle Scholar
  152. 147.
    Keay, B.A., and R. Rodrigo: A Convergent Synthesis of (+)-Daunomycinone. Tetrahedron 40, 4597 (1984).CrossRefGoogle Scholar
  153. 148.
    Sibi, M.P., N. Altintas, ans V. Scieckus: Benzamide Directed Ortho Metalation. A Route to the A/B Ring Synthon of Daunomycinone. Tetrahedron 40, 4593 (1984).CrossRefGoogle Scholar
  154. 149.
    Russell, R.A., A.S. Krauss, R.W. Irvine, and R.N. Warrener: Anthracyclines. XII. The Preparation of (—)-(7R)-7-Acetyl-7-(t-butyldimethylsiloxy)-4,4-dimethoxy5,6,7,8-tetrahydronaphthalene-1(4H)-one and (+)-(5R)-6-(t-butyldimethylsiloxy)4.4-dimethoxy-5,6,7,8-tetrahydronaphthalene-1(4H)-one: an Improved Route to Chiral AB Synthons for 7-Deoxydaunomycinone. Aust. J. Chem. 38, 179 (1985).CrossRefGoogle Scholar
  155. 150.
    Irvine, R.W., R.A. Russell, and R.N. Warrener: Allylic Vs Homoallylic Control of Stereospecifity in the Epoxidation of 3(1’-Hydroxyethyl)-5,8-dimethoxy-1,2-dihydronaphthalen-1-ol: Implications for the Synthesis of Chiral Anthracyclines. Tetrahedron Lett. 26, 6117 (1985).CrossRefGoogle Scholar
  156. 151.
    Tamoto, K., and S. Terashima: Novel Synthesis of Optically Pure Anthracyclinone Intermediates by the Use of Microbial Asymmetric Reduction with Fermenting Baker’s Yeast. Chem. Pharm. Bull. 32, 4328 (1984).CrossRefGoogle Scholar
  157. 152.
    Suzuki, M., Y. Kimura, and S. Terashima: A Novel and Highly Efficient Asymmetric Synthesis of Optically Active Anthracyclinones. Bull. Chem. Soc. Jpn. 39, 3559 (1986).CrossRefGoogle Scholar
  158. 153.
    Bauman, J.G., R.C. Hawley, and H. Rapoport: An Efficient Synthesis of Aklavinone and Related 11-Deoxyanthracyclinones. J. Org. Chem. 50, 1569 (1985).CrossRefGoogle Scholar
  159. 154.
    Bauman, J.G., R.C. Hawley, and H. Rapoport: Synthesis of a Cyclohexadiene Monoepoxide by Intramolecular Darzens Condensation. Efficient Synthesis of an A-Ring Anthracyclinone Precursor. J. Org. Chem. 49, 3791 (1984).CrossRefGoogle Scholar
  160. 155.
    Dimroth, O., and T. Faust: Über die Borsäureester der Oxyanthrachinone. Ber. dtsch. chem. Ges. 54, 3020 (1921).Google Scholar
  161. 156.
    Meyers, A.I., and K. Higashiyama: Asymmetric Additions to Chiral Naphthalenes. 4. An Asymmetric Synthesis of the AB-Ring of Aklavinone. J. Org. Chem. 52, 4592 (1987).CrossRefGoogle Scholar
  162. 157.
    Penco, S., F. Angelucci, M. Ballabio, G. Barchelli, A. Suarato, E. Vanotti, A. Vigevani, and F. Arcamone: Regiospecific Total Synthesis of 6-Deoxyanthracyclines. Tetrahedron 40, 4677 (1984).CrossRefGoogle Scholar
  163. 158.
    Synthesis and Ring Conformation of New Anthracyclines. Heterocycles 21, 21 (1984).Google Scholar
  164. 159.
    Angelucci, F., G. Barchielli, G.A. Brussani, M. Gigli, B. Gioia, R. Hermann, A. Suarato, E. Vanotti, and S. Penco: Flexible Synthetic Route to 6-Deoxy and 11-Deoxyanthracyclinones. Tetrahedron Lett. 26, 5693 (1985).CrossRefGoogle Scholar
  165. 160.
    Kelly, T.R., and W.-G. Tsang: The Synthesis of 4-Demethoxydaunomycinone. Tetrahedron Lett. 1978, 4457.Google Scholar
  166. 161.
    Lee, W.W., A.P. Martinez, T.H. Smith, and D.W. Henry: Daunomycinone Analogues via the Diels-Alder Reaction. Synthesis and Chemistry of Some 6,11-Dihydroxy-5,12-naphthacenediones. J. Org. Chem. 41, 2296 (1976).CrossRefGoogle Scholar
  167. 162.
    Van Kleef, R.P., F.J., Potman, and H.W. Scheeren: Tailor-Made Butadienes for the Site-Selective Cycloaddition with Quinizarinquinone and Other Unsymmetrically Substituted Quinones. J. Org. Chem. 50, 1955 (1985).CrossRefGoogle Scholar
  168. 163.
    Kende, A.S., Y. Tsay, and J.E. Mills: Total Synthesis of (±)-Daunomycinone and (±)-Carminomycinone. J. Am. Chem. Soc. 98, 1967 (1976).CrossRefGoogle Scholar
  169. 164.
    Kimura, Y., M. Suzuki, T. Matsumoto, R. Abe, and S. Terashima: 2-Chloro-1,3butadiene as an Efficient Enophile in the Diels-Alder Reaction with Anthracene1,4,9,10-tetraone. A Simple Synthesis of the 4-Demethoxyanthracyclinone Intermediate. Chem. Lett. 1984, 473.Google Scholar
  170. 165.
    Smith, T.H., A.N. Fujiwara, D.W. Henry, and W.W. Lee: Synthetic Approaches to Adriamycin. Degradation of Daunorubicin to Nonasymmetric Tetracyclic Ketone and Refunctionalization of the A-ring to Adriamycin. J. Am. Chem. Soc. 97, 1969 (1976).CrossRefGoogle Scholar
  171. 166.
    Suzuki, M., T. Matsumoto, R. Abe, Y. Kimura, and S. Terashima: A Simple and Efficient Synthesis of Key Synthetic Intermediates of 4-Demethoxyanthracyclinones, (±)- and (R)-(—)-7-Deoxy-4-demethoxydaunomycinone. Chem. Lett. 1985, 57.Google Scholar
  172. 167.
    Gesson, J.P., J.C. Jacqufsy, and M. Mondon: Cycloaddition d’acetals de cétènes silylés avec diverses naphthoquinones. Méthode générale de synthèse d’intermediates en série anthracycline. Nouv. J. Chim. 7, 205 (1983).Google Scholar
  173. 168.
    PRESTON, P.N., and T. WINWICK: Synthesis of Intermediates related to 11-Deoxyanthracyclinones. J. Chem. Soc. Perkin Trans. 1 1985, 39.Google Scholar
  174. 169.
    Bauman, J.G., R.B. Barber, R.D. Gless, and H. Rapoport: The Vinylketene Ace-tale Route to Aklavinone and 11-Deoxydaunomycinone. Tetrahedron Lett. 21, 4777 (1980).CrossRefGoogle Scholar
  175. 170.
    Tamura, Y., A. Wada, M. Sasho, K. Fukunaga, H. Maeda, and Y. Kita: A New General Regiocontrolled Synthesis of Anthracyclinones Using Cycloaddition of Homophthalic Anhydrides to 2-Chloro-6-oxo-5,6,7,8-tetrahydro-1,4-naphthoquinone 1,2-Ethanediyl Acetal. J. Org. Chem. 47, 4376 (1982).CrossRefGoogle Scholar
  176. 171.
    Vedejs, E., W.H. Miller, and J.R. Pribish: Silicon-Mediated Synthesis of 11-Deoxyanthracyclines. J. Org. Chem. 48, 3613 (1983).CrossRefGoogle Scholar
  177. 172.
    Tamura, Y., M. Sasho, S. Akai, A. Wada, and Y. Kita: Anthracyclinone Synthesis Using Strong Base Induced Cycloaddition of Homophthalic Anhydrides and Related Compounds. Tetrahedron 40, 4539 (1984).CrossRefGoogle Scholar
  178. 173.
    Krohn, K., and W. Baltus: Synthesis of Daunomycinone via Intramolecular Nucleophilic Addition to 9,10-Anthraquinones. Synthesis 1986, 942.Google Scholar
  179. 174.
    Khanapure, S.P., R.T. Reddy, and E.R. Biehl: The Preparation of Anthaquinones and Anthracyclinones via the Reaction of Haloarenes and Cyanophthalides under Aryne-Forming Conditions. J. Org. Chem. 52, 5685 (1987).CrossRefGoogle Scholar
  180. 175.
    Farina, F., T. Molina, and M.C. Paredes: Synthesis, Tautomerism and Diels-Alder Reactions of 1,4-Dihydroxy-9,10-anthraquinon-9-imines. Tetrahedron Lett. 26, 111 (1985).CrossRefGoogle Scholar
  181. 176.
    Russell, R.A., G.J. Collin, M. Sterns, and R.N. Warrener: Cycloaddition Routes to Polycyclic Quinones: Part 1; Boron Triacetate as a Regiochemical Directing Agent. Tetrahedron Lett. 1979, 4229.Google Scholar
  182. 177.
    Rao, A.V.R., G. Venkatswamy, S.M. Jawed, V.H. Deshpande, and B.R. Rao: Synthesis of (±)-4-Demethoxydaunomycinone. J. Org. Chem. 48, 1552 (1983).CrossRefGoogle Scholar
  183. 178.
    Gupta, D.N., P. Hodge, and N. Khan: Chemistry of Quinones. Part 7. Synthesis of Anthracyclinone Anologues via Diets-Alder Reactions of 1,4-Anthraquinones. J. Chem. Soc. Perkin Trans. 1 1981, 689.Google Scholar
  184. 179.
    Farina, F., and P. Prados: Synthesis of Tetracyclic Hydroxyketones Related to Daunomycinone. Tetrahedron Lett. 1979, 477.Google Scholar
  185. 180.
    Krohn, K., and K. Tolkiehn: Synthetische Anthracyclinone, VIII. Totalsynthese des Daunomycinons. Chem. Ber. 112, 3453 (1979).CrossRefGoogle Scholar
  186. 181.
    Krohn, K., and K. Tolkiehn: Synthetische Anthracyclinone, XIV. Synthese neuer Derivate des Daunomycinons und des 13-Rhodomycinons. Chem. Ber. 113, 2976 (1980).CrossRefGoogle Scholar
  187. 182.
    Krohn, K., K. Tolkiehn, V. Lehne, H.W. Schmalle, and H.-F. Grützmacher: Synthetic Anthracyclinones, XXIX. Quinone Antibiotics with Five Substituents at the Hydroaromatic Ring. Liebigs Ann. Chem. 1985, 1311.Google Scholar
  188. 183.
    Tamirez, J., and P. Vogel: A Doubly Convergent and Regioselective Synthesis of (+)-Daunomycinone. Tetrahedron 40, 4549 (1984).CrossRefGoogle Scholar
  189. 184.
    Gupta, R.C., P.A. Harland, and R.J. Stoodley: An Efficient Enantiocontrolled Synthesis of (+)-4-Demethoxydaunomycinone. Tetrahedron 40, 4657 (1984).CrossRefGoogle Scholar
  190. 185.
    Gupta, R.C., D.A. Jackson, R.J. Stoodley, and D.J. Williams: Studies Related to Anthracyclinones. Part 2. Synthesis of (+)-4-Demethoxydaunomycinone. J. Chem. Soc. Perkin Trans. 1 1985, 525.Google Scholar
  191. 186.
    Trost, B.M., D. O’Krongly, and J.L. Belletire: A Model for Asymmetric Induction in the Diels-Alder Reaction. J. Am. Chem. Soc. 102, 7595 (1980).Google Scholar
  192. 187.
    Krohn, K., and W. Baltus: Synthesis of roc-and ent-Fridamycin E. Tetrahedron 44, 49 (1988).CrossRefGoogle Scholar
  193. 188.
    Krohn, K., and B. Sarsted: Facile Synthesis of the (+)-6-Deoxycarminomycinone from Aloe-emodine. Angew. Chem. 95, 897 (1983); Angew. Chem. Int. Ed. 22, 875 (1983).Google Scholar
  194. 189.
    Bennani, F., J.-C. Florent, M. Koch, and C. Monneret: An Efficient Synthesis of Optically active 4-Demethoxy Anthracyclinones. Tetrahedron 40, 4669 (1984).CrossRefGoogle Scholar
  195. 190.
    Mincher, D.J., G. Shaw, and E. De Clercq: Anthracyclinones. Part 1. A Versatile Synthesis of the Anthracyclinone System using a Chiral Template derived from a Carbohydrate. J. Chem. Soc. Perkin Trans. I 1983, 613.Google Scholar
  196. 191.
    Krohn, K., U. Dötz, W. Priyono, B. Sarstedt, and A. Stoffregen: IntramOlekulare Addition von Carbanionen an Anthrachinone. Liebigs Ann. Chem. 1984, 306.Google Scholar
  197. 192.
    Krohn, K., and W. Priyono: Simple Synthesis of Anthracyclinones by Cyclization of an Intermediate Hydroxynitronate. Angew. Chem. 98, 338 (1986); Angew. Chem. Int. Ed. Engl. 25, 339 (1986).Google Scholar
  198. 193.
    Cava, M.P., Z. Ahmed, N. Benfaremo, R.A. Murphy JR., and G.J. O’Malley: Anthraquinone Dye Intermediates as Precursors of Aklavinone-Type Anthracyclinones. Tetrahedron 40, 4767 (1984).CrossRefGoogle Scholar
  199. 194.
    Mcnamara, J.M., and Y. Kistn: Practical Asymmetric Synthesis of Aklavinone. Tetrahedron 40, 4685 (1984).CrossRefGoogle Scholar
  200. 195.
    Krohn, K., M. Klimars, H.J. KÖhle, and E. Ebeling: Synthesis of -Pyrromycinon, 7-Deoxyauramycinone, and 7-Deoxyaklavinone via Ketoester Cyclization. Tetrahedron 40, 3677 (1984).CrossRefGoogle Scholar
  201. 196.
    Gesson, J.-P., J.-P. Jacquesy, and B. Renoux: A General and Regiospecific Route to Tetracyclic Alkenes in the 11-Deoxyanthracyclinone Series. Application to the Total Synthesis of (±)-Auramycinone. Tetrahedron 40, 4743 (1984).CrossRefGoogle Scholar
  202. 197.
    Snieckus, V.: New Directions in Heterocyclic Synthesis using Metalated Benzamides. J. Heterocycl. Chem. 7, 95 (1984).Google Scholar
  203. 198.
    Taub, D., N.N. Girotra, R.D. Hoffsommer, C.H. Kuo, H.L. Slates, S. Weber, and N.L. Wendler: Total Synthesis of the Macrolide Zearalenone. Tetrahedron 24, 2443 (1968).CrossRefGoogle Scholar
  204. 199.
    Russell, R.A., B.A. Pilley, R.W. Irvine, and R.N. Warrener: Anthracyclines, XVI. Further Comments Concerning the Phthalide Anion Annelation of Quinone Monoacetals. Aust. J. Chem. 40, 311 (1987).CrossRefGoogle Scholar
  205. 200.
    Russell, R.A., B.A. Pilley, and R.N. Warrener: A High-Yielding Synthesis of 3-Cyanophthalides. Synth. Commun. 16, 425 (1986).CrossRefGoogle Scholar
  206. 201.
    Russell, R.A., R.W. Irvine, and R.N. Warrener: The Total Synthesis of Optically Pure (9R,13S)- and (9R,13R)-7-Deoxy-13-dihydrodaunomycinone. J. Org. Chem. 51, 1595 (1986).CrossRefGoogle Scholar
  207. 202.
    Russell, R.A., A.S. Krauss, R.N. Warrener, and R.W. Irvine: A High-yielding Enantiospecific Synthesis of (—)-7-Deoxydaunomycinone (Part 9). Tetrahedron Lett. 25, 1517 (1984).CrossRefGoogle Scholar
  208. 203.
    Hauser, F.M., and V.M. Baghdanov: Regiospecific Total Synthesis of (+)-Daunomycinone from an 11-Deoxydaunomycinone Precursor. Tetrahedron 40, 4719 (1984).CrossRefGoogle Scholar
  209. 204.
    Jung, M.E., and J.A. Lowe: Synthetic Approaches to Adriamycin Involving DielsAlder Reactions of Photochemically generated Bisketenens. Total Synthesis of Islandicin and Digitopurpone. J. Org. Chem. 42, 2371 (1977).CrossRefGoogle Scholar
  210. 205.
    Nomura, K., K. Okazaki, K. Hori, and E. Yoahii: Total Synthesis of (+)-Granaticin. J. Am. Chem. Soc. 109, 3402 (1987).CrossRefGoogle Scholar
  211. 206.
    Hauser, F.M., R.P. Rhee, S. Prasanna, S.M., Weinreb, and J.H. Dodd: OrthoToluate Carbanion Chemistry: Sulfenylation and Selenation. Synthesis 1980, 72.Google Scholar
  212. 207.
    Parker, K.A., D.M. Spero, and K.A. Koziski: Evaluation of Some Preparations of Trialkoxyphthalic Acid Derivatives. J. Am. Chem. Soc. 52, 183 (1987).Google Scholar
  213. 208.
    Birch, A.J., and K.P. Dastur: A Catalytic Conversion of 1-Methoxycyclohexa-1,4dienes into 1-Methoxycyclohexa-1,3-dienes. Tetrahedron Lett. 1972, 4195.Google Scholar
  214. 209.
    Harland, P.A., and J.H. Dodd: Synthesis of Phthalates, Benzoates, and Phthalides via the in situ Generation of Methoxycyclohexa-1,3-dienes and their Subsequent Diels-Alder Reactions with Acetylenes. Synthesis 1982, 223.Google Scholar
  215. 210.
    Johnson, O.H., and J.R. Holum: 1,1-Diethoxy-3-(triphenylstannyl)-2-propyne. J. Org. Chem. 23, 738 (1958).CrossRefGoogle Scholar
  216. 210a.
    Tamura, Y., M. Sasho, S.Akai, H. Kishimoto, J. S.Kihachi, and Y. Kita: An Efficient, Regiospecific Synthesis of 4-Demethoxydaunomycinone and Daunomycinone. Chem. Pharm. Bull. 35, 1405 (1987).Google Scholar
  217. 211.
    Ravichandran, K., F.A.J. Kerdesky, and M.P. Cava: Synthesis of 4-Demethoxy6,11-dideoxydaunomycinone. A Highly Deoxygenated Anthracyclinone. J. Org. Chem. 51, 2044 (1986).CrossRefGoogle Scholar
  218. 212.
    Vedejs, E.V., and J.R. Pribish: A Synthesis of the C6,C11-Dideoxyanthracyclinone Skeleton via Hassall Cyclization and Oxidative Desililation. J. Org. Chem. 53, 1593 (1988).CrossRefGoogle Scholar
  219. 213.
    Matsumoto, T., M. Ohsaki, F. Matsuda, and S. Terashima: Effecient Synthesis and Antitumor Activity of Novel 14-Fluoroanthracyclines. Tetrahedron Lett. 28, 4419 (1987).CrossRefGoogle Scholar
  220. 214.
    Lown, J.W., and S.M. Sondhi: Glycosidic Coupling of Regiospecifically Synthesized Xantho[2,3-g]tetralin Aglycones to Afford Moderately Antileukemic but Redox Inactive Structures Related to Anthracyclines. J. Org. Chem. 50, 1413 (1985).CrossRefGoogle Scholar
  221. 215.
    Wong C.-M., W. Haque, H.-Y. Lam, K. Marat, and E. Bock: Heteroanthracyclines. 1,4-Demethoxyxanthodaunomycinone (6,7,9,11-tetrahydroxy-9-acetyl7,8,9,10-tetrahydrobenzo(B)xanthen-12-one). Can. J. Chem. 61, 1788 (1983).CrossRefGoogle Scholar
  222. 216.
    Kende, A.S., and H. Newmann: Eur. Pat. Appl. (1980); CA: 94, 140117j (1981).Google Scholar
  223. 217.
    Kawasaki, M., F. Matsuda, and T. Terashima: First Total Synthesis of (+)-7Deoxynogarol and (+)-7-Con-O-methylnogarol. Tetrahedron Lett. 29, 791 (1988).CrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1989

Authors and Affiliations

  • K. Krohn
    • 1
  1. 1.Institut für Organische ChemieTechnischen UniversitätBraunschweigFederal Republic of Germany

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