Efficient Synthesis of Polycycles by Electrocyclizations of Substituted Trihydroxybenzenes: Synthesis of Rubranine and Deoxybruceol

Abstract

A new synthetic route for biologically interesting polycycles with a citran and a cyclol nucleus was developed starting from several substituted trihydroxybenzenes. This methodology was applied successfully to the synthesis of two natural products, rubranine and deoxybruceol.

polycycles - citran - cyclol - electrocyclization - rubranine - deoxybruceol

References and Notes

<A NAME="RU05307ST-1A">1a</A> Bukuru J. Van T N. Puyvelde LV. He W. De Kimpe N. Tetrahedron  2003,  59:  5905 

<A NAME="RU05307ST-1B">1b</A> Begley MJ. Crombie L. King RW. Slack DA. Whiting DA. J. Chem. Soc., Chem. Commun.  1977,  2393 

<A NAME="RU05307ST-1C">1c</A> Mechoulam R. Gaoni Y. Fortschr. Chem. Org. Naturst.  1967,  25:  175 

<A NAME="RU05307ST-1D">1d</A> Claussen U. von Spulak F. Korte F. Tetrahedron  1968,  24:  1021 

<A NAME="RU05307ST-1E">1e</A> Crombie L. Ponsford R. Shani A. Yagnitinsky B. Mechoulan R. Tetrahedron Lett.  1968,  5771 

<A NAME="RU05307ST-1F">1f</A> Crombie L. Ponsford R. J. Chem. Soc., Chem. Commun.  1968,  894 

<A NAME="RU05307ST-2A">2a</A> Turner CE. Elsohly MA. Boeren EG. J. Nat. Prod.  1980,  43:  169 

<A NAME="RU05307ST-2B">2b</A> Cui C.-B. Yan S.-Y. Cai B. Yao X.-S. J. Asian Nat. Prod. Res.  2002,  4:  233 

<A NAME="RU05307ST-3A">3a</A> Crombie L. Crombie WML. Phytochemistry  1975,  14:  213 

<A NAME="RU05307ST-3B">3b</A> Shoyama Y. Morimoto S. Nishioka I. Chem. Pharm. Bull.  1981,  29:  3720 

<A NAME="RU05307ST-3C">3c</A> Kane V. Martin AR. Peters JA. J. Org. Chem.  1984,  49:  1793 

<A NAME="RU05307ST-3D">3d</A> Gaoni Y. Mechoulam R. J. Am. Chem. Soc.  1971,  93:  217 

<A NAME="RU05307ST-4A">4a</A> Devane WA. Dysarz FA. Johnson MR. Melvin LS. Howlett AC. Mol. Pharmacol.  1988,  34:  606 

<A NAME="RU05307ST-4B">4b</A> Matsuda LA. Lolait SJ. Brownstein MJ. Young AC. Bonner TI. Nature (London)  1990,  346:  561 

<A NAME="RU05307ST-4C">4c</A> Munro S. Thomas KL. Abu-Shaar M. Nature (London)  1993,  365:  61 

<A NAME="RU05307ST-5">5</A> De Alleluia IB. Brez Fo R. Gottlieb OR. Magalhaes EG. Marques R. Phytochemistry  1978,  17:  517 

<A NAME="RU05307ST-6A">6a</A> Delespaul Q. De Billerbeck VG. Roques CG. Michel G. Marquir-Vinuales C. Bessiere J.-M. J. Essent. Oil Res.  2000,  12:  256 

<A NAME="RU05307ST-6B">6b</A> Hammer KA. Carson CF. Riley TV. J. Appl. Microbiol.  1999,  86:  985 

<A NAME="RU05307ST-7">7</A> Ahluwalia VK. Sharma ND. Mittal B. Gupta SR. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1988,  27:  238 

<A NAME="RU05307ST-8A">8a</A> Singh R. Singhal KC. Khan NU. Indian J. Physiol. Pharmacol.  1997,  41:  397 

<A NAME="RU05307ST-8B">8b</A> Daikonya A. Katsuki S. Wu J.-B. Kitanaka S. Chem. Pharm. Bull.  2002,  50:  1566 

<A NAME="RU05307ST-9A">9a</A> Srivastava MC. Singh SW. Tewari JP. Ind. J. Med. Res.  1967,  55:  746 

<A NAME="RU05307ST-9B">9b</A> Gupta SS. Verma P. Hishikar K. Indian J. Physiol. Pharmacol.  1984,  19:  103 

<A NAME="RU05307ST-9C">9c</A> Lounasmaa M. Widen CJ. Tuuf CM. Huhtikangas A. Planta Med.  1975,  28:  16 

<A NAME="RU05307ST-10A">10a</A> Rashid MA. Armstrong JA. Gray AI. Waterman PG. Phytochemistry  1992,  31:  3583 

<A NAME="RU05307ST-10B">10b</A> Gray AI. Rashid MA. Waterman PG. J. Nat. Prod.  1992,  55:  681 

<A NAME="RU05307ST-11A">11a</A> Kane VV. Grayeck TL. Tetrahedron Lett.  1971,  3991 

<A NAME="RU05307ST-11B">11b</A> Crombie L. Ponsford R. J. Chem. Soc. C.  1971,  788 

<A NAME="RU05307ST-11C">11c</A> Crombie L. Redshaw SD. Slack DA. Whiting DA. J. Chem. Soc., Chem. Commun.  1979,  628 

<A NAME="RU05307ST-12A">12a</A> Lee YR. Choi JH. Yoon SH. Tetrahedron Lett.  2005,  46:  7539 

<A NAME="RU05307ST-12B">12b</A> Lee YR. Kim DH. Synthesis  2006,  603 

<A NAME="RU05307ST-12C">12c</A> Lee YR. Choi JH. Trinh DTL. Kim NW. Synthesis  2005,  3026 

<A NAME="RU05307ST-12D">12d</A> Lee YR. Lee WK. Noh SK. Lyoo WS. Synthesis  2006,  853 

<A NAME="RU05307ST-13">13</A>

Spectral data for 11: ¹H NMR (300 MHz, CDCl₃): δ = 14.03 (1 H, s), 6.67 (1 H, d, J = 10.1 Hz), 6.61 (1 H, d, J = 10.1 Hz), 5.38 (1 H, d, J = 10.1 Hz), 5.37 (1 H, d, J = 10.1 Hz), 5.10-5.03 (4 H, m), 2.64 (3 H, s), 2.20-1.87 (14 H, m), 1.79-1.65 (2 H, m), 1.65 (6 H, s), 1.56 (6 H, s), 1.55 (6 H, s), 1.43 (3 H, s), 1.40 (3 H, s). IR (neat): 2926, 1640, 1601, 1429, 1366, 1296, 1154, 1105, 1026, 1001, 895, 729 cm^-1. HRMS: m/z [M⁺] calcd for C₃₈H₅₂O₄: 572.3866; found: 572.3868.

<A NAME="RU05307ST-14">14</A>

Spectral data for 12: ¹H NMR (300 MHz, CDCl₃): δ = 13.29 (1 H, s), 6.01 (1 H, s), 5.18-5.13 (1 H, m), 2.72 (1 H, br s), 2.58 (3 H, s), 2.28-1.98 (8 H, m), 1.69 (3 H, s), 1.63 (3 H, s), 1.50-1.40 (1 H, m), 1.36 (3 H, s), 1.32-1.23 (2 H, m) 1.05 (3 H, s). IR (neat): 2928, 1622, 1485, 1433, 1364, 1294, 1161, 1061, 961, 824, 772, 735 cm^-1. HRMS: m/z [M⁺] calcd for C₂₃H₃₀O₄: 370.2144; found: 370.2142

<A NAME="RU05307ST-15">15</A>

Spectral data for 23: mp 216-217 °C. ¹H NMR (300 MHz, CDCl₃): δ = 13.95 (1 H, s), 8.19 (1 H, d, J = 15.7 Hz), 7.74 (1 H, d, J = 15.7 Hz), 7.51 (2 H, d, J = 8.1 Hz), 7.17 (2 H, d, J = 8.1 Hz), 6.08 (1 H, s), 2.77 (1 H, br s), 2.37 (3 H, s), 2.24-2.06 (2 H, m), 1.88-1.82 (1 H, m), 1.64 (3 H, s), 1.50-1.41 (1 H, m), 1.38 (3 H, s), 1.30-1.24 (1 H, m), 1.05 (3 H, s), 0.87-0.83 (2 H, m). IR (KBr): 3449, 2924, 1618, 1549, 1478, 1235, 1181, 1163, 1142, 1078, 1020, 988, 881, 823 cm^-1. HRMS: m/z [M⁺] calcd for C₂₆H₂₈O₄: 404.1988; found: 404.1985.

<A NAME="RU05307ST-16">16</A>

Spectral data for 24: mp 208-209 °C. ¹H NMR (300 MHz, CDCl₃): δ = 14.04 (1 H, s), 8.13 (1 H, d, J = 15.6 Hz), 7.74 (1 H, d, J = 15.6 Hz), 7.56 (2 H, d, J = 8.7 Hz), 7.17 (2 H, d, J = 8.7 Hz), 6.08 (1 H, s), 3.84 (3 H, s), 2.77 (1 H, br s), 2.22-2.08 (2 H, m), 1.88-1.83 (1 H, m), 1.64 (3 H, s), 1.50-1.40 (1 H, m), 1.38 (3 H, s), 1.32-1.23 (1 H, m), 1.05 (3 H, s), 0.92-0.80 (2 H, m). IR (KBr): 3445, 1622, 1553, 1510, 1480, 1422, 1352, 1233, 1171, 1022, 829 cm^-1. HRMS: m/z [M⁺] calcd for C₂₆H₂₈O₅: 420.1937; found: 420.1938.

<A NAME="RU05307ST-17">17</A> Saimoto H. Yoshida K. Murakami T. Morimoto M. Sashiwa H. Shigemasa Y. J. Org. Chem.  1996,  61:  6768 

<A NAME="RU05307ST-18">18</A> Crombie L. Redshaw SD. Whiting DA. J. Chem. Soc., Chem. Commun.  1979,  63 

<A NAME="RU05307ST-19">19</A>

Typical Procedure for Compounds 12 and 16-22
To a solution of trihydroxybenzenes (1.0 mmol) and citral or trans,trans-farnesal (2.0 mmol) in DMF (20 mL) was added ethylenediamine diacetate (36 mg, 0.2 mmol) at r.t. The reaction mixture was stirred at 100 °C for 10-12 h and then cooled to r.t. Then H₂O was added and the solution was extracted with EtOAc. Evaporation of solvent and purification by column chromatography on silica gel gave the products.