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Synlett 2012(5): 768-772  
DOI: 10.1055/s-0031-1290529
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Diels-Alder Approach to Anthrapyran Antibiotics

Laura Foulgoca, Drissa Sissoumaa,b, Michel Evainc, Sylvain Collet*a, André Guingant*a
a Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, 2 Rue de la Houssinière, BP 92208, 44322 Nantes Cedex 03, France
Fax: +33(2)51125402; e-Mail: andre.guingant@univ-nantes.fr; e-Mail: sylvain.collet@univ-nantes.fr;
b Laboratoire de Chimie Organique Structurale, UFR SSMT, Université de Cocody-Abidjan, Abidjan, Ivory Coast
c Institut des Matériaux Jean Rouxel, 2 Rue de la Houssinière, BP 92208, 44322 Nantes Cedex 03, France
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Publication History

Received 24 November 2011
Publication Date:
24 February 2012 (online)

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Abstract

A new entry to the synthesis of anthrapyran antibiotics has been accomplished through the synthesis of a 4H-anthra[1,2-b]pyran-4,7,12-trione model. The key step features a Diels-Alder reaction between a substituted 5-vinyl-3,4-dihydro-2H-pyran and naphthoquinone as the dienophile. The resulting tetracyclic adduct is then processed towards the targeted trione in a few steps.

Key words

anthrapyran antibiotics - Diels-Alder reaction - quin­ones - Stille reaction - 4H-anthra[1,2-b]pyran-4,7,12-trione

    References and Notes

  • 1 Hansen MR. Hurley LH. Acc. Chem. Res.  1996,  29:  249 
    Google Scholar
  • 2a Fei ZB. McDonald FE. Org. Lett.  2007,  9:  3547 
    Google Scholar
  • 2b O’Keefe BM. Mans DM. Kaelin DE. Martin SF. J. Am. Chem. Soc.  2010,  132:  15528 
    Google Scholar
  • 3a Hauser FM. Rhee RP. J. Am. Chem. Soc.  1979,  101:  1628 
    Google Scholar
  • 3b Hauser FM. Rhee RP. J. Org. Chem.  1980,  45:  3061 
    Google Scholar
  • 3c Uno H. Sakamoto K. Honda E. Fukuhara K. Ono N. Tanaka J. Sakanaka M. J. Chem. Soc., Perkin Trans. 1  2001,  229 
    Google Scholar
  • 3d Krohn K. Vitz J. Eur. J. Org. Chem.  2004,  209 
    Google Scholar
  • 3e Fei ZB. McDonald FE. Org. Lett.  2005,  7:  3617 
    Google Scholar
  • 3f Krohn K. Vidal A. Vitz J. Westermann B. Abbas M. Green I. Tetrahedron: Asymmetry  2006,  17:  3051 
    Google Scholar
  • 3g Tietze LF. Gericke KM. Singidi RR. Angew. Chem. Int. Ed.  2006,  45:  6990 
    Google Scholar
  • 3h Tietze LF. Singidi RR. Gericke KM. Org. Lett.  2006,  8:  5873 
    Google Scholar
  • 3i Krohn K. Tran-Thien HT. Vitz J. Vidal A. Eur. J. Org. Chem.  2007,  1905 
    Google Scholar
  • 3j Tietze LF. Singidi RR. Gericke KM. Chem. Eur. J.  2007,  13:  9939 
    Google Scholar
  • 3k Gattinoni S. Merlini L. Dallavalle S. Tetrahedron Lett.  2007,  48:  1049 
    Google Scholar
  • 3l Wright BJD. Hartung J. Peng F. Van de Water R. Liu H. Tan Q.-H. Danishefsky SJ. J. Am. Chem. Soc.  2008,  130:  16786 
    Google Scholar
  • 3m Dallavalle S. Gattinoni S. Mazzini S. Scaglioni L. Merlini L. Tinelli S. Beretta GL. Zunino F. Bioorg. Med. Chem. Lett.  2008,  18:  1484 
    Google Scholar
  • 3n Elban MA. Hecht SM. J. Org. Chem.  2008,  73:  785 
    Google Scholar
  • 4a Collet S. Remi J.-F. Cariou C. Laib S. Guingant A. Vu N.-Q. Dujardin G. Tetrahedron Lett.  2004,  45:  4911 
    Google Scholar
  • 4b Vu N.-Q. Dujardin G. Collet S. Raiber E.-A. Guingant A. Evain M. Tetrahedron Lett.  2005,  46:  7669 
    Google Scholar
  • 4c Sissouma D. Maingot L. Collet S. Guingant A. J. Org. Chem.  2006,  71:  8384 
    Google Scholar
  • 4d Maingot L. Thuaud F. Sissouma D. Collet S. Guingant A. Evain M. Synlett  2008,  263 
    Google Scholar
  • 5a Danishefsky SJ. Larson E. Askin D. Kato N. J. Am. Chem. Soc.  1985,  107:  1246 
    Google Scholar
  • 5b Danishefsky SJ. Pearson WH. Harvey DF. Maring CJ. Springer JP. J. Am. Chem. Soc.  1985,  107:  1256 
    Google Scholar
  • Examples of dihydropyran-4-one iodination:
  • 6a Chemler SR. Iserloh U. Danishefsky SJ. Org. Lett.  2001,  3:  2949 
    Google Scholar
  • 6b Gardiner JM. Mills R. Fessard T. Tetrahedron Lett.  2004,  45:  1215 
    Google Scholar
  • 6c Leonelli F. Capuzzi M. Calcagno V. Passacantilli P. Piancatelli G. Eur. J. Org. Chem.  2005,  2671 
    Google Scholar
  • 7a Luche J.-L. Gemal AL. J. Am. Chem. Soc.  1979,  101:  5848 
    Google Scholar
  • 7b Danishefsky SJ. Bednarski M. Tetrahedron Lett.  1985,  26:  3411 
    Google Scholar
  • 8 Seyferth D. Stone FGA. J. Am. Chem. Soc.  1957,  79:  515 
    Google Scholar
  • 9 For a Lewis acid catalysed cycloaddition with a related diene, see: Huang H.-L. Liu R.-S. J. Org. Chem.  2003,  68:  805 
    Google Scholar
  • 11 For an analysis of substituent effects on regioselectivities of cycloadditions to naphthoquinones, see: Rozeboom MD. Tegmo-Larsson I.-M. Houk KN. J. Org. Chem.  1981,  46:  2338 
    Google Scholar
  • 13 For an example of B-ring aromatisation via an epoxide in the field of angucyclines, see: Krohn K. Micheel J. Tetrahedron  1998,  54:  4827 ; aromatisation of 14 could be explained by aerial oxidation of ring C followed by abstraction of a proton at C6 (or C12c) of ring B with subsequent opening of the epoxide and dehydration of the resulting alcohol
    Google Scholar
  • 14 Tan Z. Wang L. Wang J. Chin. Chem. Lett.  2000,  11:  753 
    Google Scholar
  • 15 Patonay T. Cavaleiro J. Lévai A. Silva A. Heterocycl. Commun.  1997,  3:  223 
    Google Scholar
10

Procedure for the Preparation of 3b
To a solution of (2-benzyloxymethyl-5-vinyl-3,4-dihydro-2H-pyran-4-yloxy)-tert-butyl(dimethyl)silane (diene 6, 890 mg, 2.45 mmol) in MeCN (13 mL) was added 1,4-naphtho-quinone (4, 465 mg, 2.94 mmol). The reaction was stirred for 24 h at r.t. H2O (30 mL) was then added, and the aqueous layer was extracted with CH2Cl2 (2 × 50 mL). The combined organic phases were dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel column chromatography (Et2O-PE = 1:4) to yield Diels-Alder adduct 3b (1.18 g, 77%) as a white solid (mp 97 ˚C). ¹H NMR (400 MHz, CDCl3): δ = 8.07-8.02 (m, 1 H, H11), 7.95-7.89 (m, 1 H, H8), 7.65-7.59 (m, 2 H, H9 and H10), 7.34-7.18 (m, 5 H, H-Ph), 5.81 (dd, J 5-6 = 5.9 Hz, J 5-6 ′ = 1.6 Hz, 1 H, H5), 4.79 (dd, J 12b-12a = 5.2 Hz, J 12b-6b = 1.2 Hz, 1 H, H12b), 4.30 (X part of an ABX system, J XA = 4.2 Hz, J XB = 3.7 Hz, 1 H, H4), 4.31 and 4.26 (AB system, J AB = 12.0 Hz, 2 H, CH2Ph), 3.76 and 3.32 (AB part of an ABX system, J AB = 11.0 Hz, J AX = 7.6 Hz, J BX = 4.5 Hz, 2 H, CH2O), 3.64-3.56 (m, X part of 2 ABX systems, 1 H, H2), 3.44 (M part of an AMX system, J 12a-12b = 5.2 Hz, J 12a-6a = 5.8 Hz, 1 H, H12a), 3.37 (M part of an ABMX system, J 12a-6a = 5.8 Hz, J 6a-6 = 6.0 Hz, J 6a-6 ′ = 1.2 Hz, 1 H, H6a), 3.0 and 2.13 (AB part of an ABXY system, J AB = 18 Hz, J 6-7 = 6 Hz, J 6-6a = 1.2 Hz, J 6 ′ -6a = 6.0 Hz, J 6 ′ -5 = 1.6 Hz, J 6 ′ -12b = 1.2 Hz, 2 H, H6 and H6 ′), 1.92 and 1.66 (AB part of ABXY system, J AB = 14.1 Hz, J 3-2 = 6.0 Hz, J 3-4 = 4.2 Hz, J 3 ′ -4 = 3.7 Hz, J 3 ′ -2 = 3.7 Hz, 2 H, H3 and H3 ′), 0.84 (s, 9 H, H22), 0.02 (s, 3 H, H20), -0.01 (s, 3 H, H20 ′). ¹³C NMR (75 MHz, CDCl3): δ = 197.5 and 196.44 (2 Cq, C7 and C12), 138.7 (Cq, C16), 137.2 and 136.4 (2 Cq, C7a and C11a), 136.8 (Cq, C4a), 133.5 and 133.1 (2 CH, C9 and C10), 128.2 (2 CH, C17 and C17 ′), 127.5 (2 CH, C18 and C18 ′), 127.3 (CH, C19), 126.2 and 125.7 (2 CH, C8 and C11), 121.6 (CH, C5), 72.8 (CH, C2), 72.5 (CH2, C15), 70.8 (CH, C4), 70.7 (CH2, C13), 63.1 (CH, C12b), 51.8 (CH, C12a), 43.65 (CH, C6a), 37.4 (CH2, C3), 25.7 (3 CH3, C22), 22.31 (CH2, C6), 17.9 (Cq, C21), -4.6 (CH3, C20), -5.1 (CH3, C20’). IR (KBr): 2930, 1699, 1254, 1095, 1052 cm-¹. MS (EI): m/z (%) = 386 (16), 370 (8), 353 (14), 327 (7), 295 (7), 265 (13), 261 (7), 133 (22) 91 (100), 73 (25). MS (CI, NH3): m/z = 536 [(M + NH4)+]. HRMS (Maldi DHB/MeCN + PEG600): m/z calcd for C31H38O5SiNa [MNa]+: 541.2381; found: 541.2397, Δ = 2.3 ppm.

12

Crystal Structure Data for 17
C31H38O6Si, M r = 534.7, monoclinic, P21/c, a = 11.1097 (11), b = 18.9124 (12), c = 13.8124 (15) Å, β = 106.699 (9), V = 2779.7 (5) ų, Z = 4, ρ calcd = 1.2773 g cm-³, µ = 1.27 mm-¹, F(000) = 1144, colourless block, 0.19 × 0.18 × 0.17 mm³, 2θ max = 56˚, T = 120 K, 48226 reflections, 6629 unique (98% completeness), R int = 0.096, 346 parameters, GOF = 1.54, wR2 = 0.1231, R = 0.0563 for 4795 reflections with I > 2σ(I). CCDC 855339 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

16

Spectroscopic Data for Trione 1
Tan solid (mp 165 ˚C). ¹H NMR (300 MHz, CDCl3): δ = 8.63 (d, J 6-5 = 8.3 Hz, 1 H, H6), 8.37 (d, J 5-6  = 8.3 Hz, 1 H, H5), 8.33-8.27 (m, 2 H, H8 and H11), 7.90-7.79 (m, 2 H, H9 and H10), 7.49-7.30 (m, 5 H, H-Ph), 6.68 (s, 1 H, H3), 4.80 (s, 2 H, CH2Ph), 4.57 (d, J = 0.8 Hz, 2 H, CH2O). ¹³C NMR (100 MHz, CDCl3): δ = 182.4 and 181.3 (2 Cq, C7 and C12), 176.6 (Cq, C4), 167,6 (Cq, C12b), 154.7 (Cq, C2), 137.9 (Cq, C6a), 137.1 (Cq, C16), 134.9 and 134.2 (2 CH, C9 and C10), 134.3 (Cq, C11a), 132.3 (Cq, C7a), 132.1 (CH, C6), 128.8 (2 CH, C17, C17 ′), 128.5 (Cq, C4a), 128.3 (CH, C19), 128.0 (2 CH, C18 and C18 ′), 127.3 and 127.2 (2 CH, C8 and C11), 123.3 (CH, C5), 122.7 (Cq, C12a), 110.1 (CH, C3), 73.8 (CH2, C15), 67.9 (CH2, C13). IR (KBr): 1674, 1657, 1589, 1418, 1324, 1283, 1122 cm-¹. MS (EI): m/z (%) = 280 (20), 125 (27), 111 (30), 97 (47), 83 (45), 71 (59), 57 (100), 43 (69). MS (CI, NH3): m/z = 397 [(M + H)+]. ESI-HRMS: m/z calcd for C25H17O5 [MH]+: 397.1071; found: 397.1056, Δ = 3.6 ppm.