Total Synthesis of Luotonin and a Small Library of AB-Ring Substituted Analogues by Cascade Radical Annulation of Isonitriles

Raghuraman Tangirala; Smitha Antony; Keli Agama; Yves Pommier; Dennis P. Curran

doi:10.1055/s-2005-918923

LETTER

Total Synthesis of Luotonin and a Small Library of AB-Ring Substituted
Analogues by Cascade Radical Annulation of Isonitriles

Raghuraman Tangirala^a, Smitha Antony^b, Keli Agama^b, Yves Pommier^b, Dennis P. Curran*^a
^a Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax: +1(412)6249861; e-Mail: curran@pitt.edu;
^b Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, Bethesda, MD 20892, USA

Abstract

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Abstract

A four-step total synthesis of luotonin is deployed to make a small library of AB-ring substituted analogues. These analogues show weak activity in a standard topoisomerase I mediated DNA cleavage assay.

Key words

camptothecin - topoisomerase I inhibitor - luotonin - isonitrile radical annulation

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References

<A NAME="RY06205ST-1">1</A> Ma ZZ. Hano Y. Nomura T. Chen Y.-J. Heterocycles 1997, 46: 541

Recent reviews on synthesis and medicinal chemistry of camptothecins:

<A NAME="RY06205ST-2A">2a</A> Thomas CJ. Rahier NJ. Hecht SM. Bioorg. Med. Chem. 2004, 12: 1585

<A NAME="RY06205ST-2B">2b</A> Du W. Tetrahedron 2003, 59: 8649

<A NAME="RY06205ST-2C">2c</A> Pizzolato JF. Saltz LB. Lancet 2003, 361: 2235

<A NAME="RY06205ST-2D">2d</A> Ulukan H. Swaan P. Drugs 2002, 62: 2039

<A NAME="RY06205ST-2E">2e</A> Kim D.-K. Lee N. Mini-Rev. Med. Chem. 2002, 2: 611

<A NAME="RY06205ST-2F">2f</A> Lerchen H.-G. Drugs Fut. 2002, 29: 869

<A NAME="RY06205ST-2G">2g</A> Zunino F. Dallavalle S. Laccabue D. Beretta G. Merlini L. Pratesi G. Curr. Pharm. Design 2002, 8: 2505

<A NAME="RY06205ST-3">3</A> Cagir A. Jones SH. Gao R. Eisenhauer BM. Hecht SM. J. Am. Chem. Soc. 2003, 125: 13628

<A NAME="RY06205ST-4A">4a</A> Du W. Curran DP. Bevins RL. Zimmer SG. Zhang J. Burke TG. Bioorg. Med. Chem. 2002, 10: 103

<A NAME="RY06205ST-4B">4b</A> Laco GS. Du W. Kohlhagen G. Sayer JM. Jerina DM. Burke TG. Curran DP. Pommier Y. Bioorg. Med. Chem. 2004, 12: 5225

<A NAME="RY06205ST-4C">4c</A> Hautefaye P. Cimetière B. Pierre A. Léonce S. Hickman J. Laine W. Bailly C. Lavelle G. Bioorg. Med. Chem. Lett. 2003, 13: 2731

<A NAME="RY06205ST-5A">5a</A> Yadav JS. Reddy BVS. Tetrahedron Lett. 2002, 43: 1905

<A NAME="RY06205ST-5B">5b</A> Wang H. Ganesan A. Tetrahedron Lett. 1998, 39: 9097

<A NAME="RY06205ST-5C">5c</A> Kelly RT. Chamberland S. Silva RA. Tetrahedron Lett. 1999, 40: 2723

<A NAME="RY06205ST-5D">5d</A> Molina P. Tárraga A. Gonzalez-Tejero A. Synthesis 2000, 1523

<A NAME="RY06205ST-5E">5e</A> Toyota M. Komori C. Ihara M. Heterocycles 2002, 56: 101

<A NAME="RY06205ST-5F">5f</A> Harayama T. Morikami Y. Shigeta Y. Abe H. Takeuchi Y. Synlett 2003, 847

<A NAME="RY06205ST-5G">5g</A> Chavan SP. Sivappa R. Tetrahedron 2004, 60: 9931

<A NAME="RY06205ST-5H">5h</A> Harayama T. Hori A. Serban G. Morikami Y. Matsumoto T. Abe H. Takeuchi Y. Tetrahedron 2004, 60: 10645

<A NAME="RY06205ST-5I">5i</A> Ma Z. Hano Y. Nomura T. Chen Y. Bioorg. Med. Chem. Lett. 2004, 14: 1193

<A NAME="RY06205ST-5J">5j</A> Twin H. Batey RA. Org. Lett. 2004, 6: 4913

<A NAME="RY06205ST-5K">5k</A> Bowman WR. Cloonan MO. Fletcher AJ. Stein T. Org. Biomol. Chem. 2005, 3: 1460

<A NAME="RY06205ST-6A">6a</A> Cagir A. Jones SH. Eisenhauer BM. Gao R. Hecht SM. Bioorg. Med. Chem. Lett. 2004, 14: 2051

<A NAME="RY06205ST-6B">6b</A> Cagir A. Eisenhauer BM. Gao R. Thomas SJ. Hecht SM. Bioorg. Med. Chem. 2004, 12: 6287

<A NAME="RY06205ST-7">7</A> Dallavalle S. Merlini L. Beretta GL. Tinelli S. Zunino F. Bioorg. Med. Chem. Lett. 2004, 14: 5757

<A NAME="RY06205ST-8A">8a</A> Curran DP. Liu H. J. Am. Chem. Soc. 1992, 114: 5863

<A NAME="RY06205ST-8B">8b</A> Curran DP. Ko SB. Josien H. Angew. Chem., Int. Ed. Engl. 1995, 34: 2683

<A NAME="RY06205ST-8C">8c</A> Curran DP. Liu H. Josien H. Ko SB. Tetrahedron 1996, 52: 11385

<A NAME="RY06205ST-8D">8d</A> Josien H. Bom D. Curran DP. Zheng Y.-H. Chou T.-C. Bioorg. Med. Chem. Lett. 1997, 7: 3189

<A NAME="RY06205ST-8E">8e</A> Josien H. Ko SB. Bom D. Curran DP. Chem.-Eur. J. 1998, 4: 67

<A NAME="RY06205ST-8F">8f</A> Curran DP. Josien H. Bom D. Gabarda A. Du W. In The Camptothecins: Unfolding their Anticancer Potential Vol. 922: Liehr JG. Giovanella BC. Verschraegen CF. NY Acad. Sci.; New York: 2000. p.112-121

<A NAME="RY06205ST-8G">8g</A> Gabarda AE. Du W. Isarno T. Tangirala RS. Curran DP. Tetrahedron 2002, 58: 6329

<A NAME="RY06205ST-8H">8h</A> Gabarda AE. Curran DP. J. Comb. Chem. 2003, 5: 617

<A NAME="RY06205ST-9">9</A> Representative experiments are provided at the end of the paper. Complete details and characterization data are in: Tangirala R. PhD Thesis University of Pittsburgh; Pittsburgh: 2005.

<A NAME="RY06205ST-10">10</A> Liu H. Ko SB. Josien H. Curran DP. Tetrahedron Lett. 1995, 36: 8917

<A NAME="RY06205ST-11">11</A> Allen CFH. Vanallen JA. Org. Synth., Coll. Vol. III Wiley; New York: 1965. p.275

<A NAME="RY06205ST-12">12</A> Antony S. Jayaraman M. Laco G. Kohlhagen G. Kohn KW. Cushman M. Pommier Y. Cancer Res. 2003, 63: 7428