A Facile and Practical Total Synthetic Route for Ampelopsin F and Permethylated ε-Viniferin

Abstract

Stilbene dimers (±)-ampelospin F and permethylated (±)-ε-viniferin were synthesized by a practical synthetic route with overall yields of 10% and 27% . This route involves triethylsilane-mediated reduction of the 2,3-diarylbenzofuran,, and BBr₃-mediated one-pot demethylation and cascade intramolecular cyclization reaction.

Key words

total synthesis - ampelopsin F - ε-viniferin - stilbene dimer - BBr₃

• References and Notes

• 1a Ha DT, Chen QC, Hung TM, Youn UJ, Ngoc TM, Thuong PT, Kim HJ, Seong YH, Min BS, Bae KH. Arch. Pharm. Res. 2009; 32: 177
• 1b Ahmat N, Wibowo A, Mohamad SA. S, Low AL. M, Sufian AS, Yusof M, Latip J. J. Nat. Prod. Res. 2014; 16: 1099
• 1c Oshima Y, Ueno Y, Hisamichi K, Takeshita M. Tetrahedron 1993; 49: 5801
• 2a Ha DT, Kim HJ, Thuong PT, Ngoc TM, Lee I, Hung ND, Bae K. J. Ethnopharmacol. 2009; 125: 304
• 2b Yim N, Trung TN, Kim JP, Lee S, Na M, Jung H, Kim HS, Kim YH, Bae K. Bioorg. Med. Chem. Lett. 2010; 20: 1165
• 3a Privat C, Telo JP, Bernardes-Genisson V, Vieira A, Souchard JP, Nepveu F. J. Agric. Food Chem. 2002; 50: 1213
• 3b Schnee S, Queiroz EF, Voinesco F, Marcourt L, Dubuis PH, Wolfender JL, Gindro K. J. Agric. Food Chem. 2013; 61: 5459
• 3c Yáñez M, Fraiz N, Cano E, Orallo F. Eur. J. Pharmacol. 2006; 542: 54
• 3d Zghonda N, Yoshida S, Ezaki S, Otake Y, Murakami C, Mliki A, Ghorbel A, Miyazaki H. Biosci. Biotechnol. Biochem. 2012; 76: 954
• 3e Lin M, Yao CS. Stud. Nat. Prod. Chem. 2006; 33: 601
• 4a Snyder SA, Zografos AL, Lin Y. Angew. Chem. Int. Ed. 2007; 46: 8186
• 4b Snyder SA, Breazzano SP, Ross AG, Lin Y, Zografos AL. J. Am. Chem. Soc. 2009; 131: 1753
• 4c Lindgren AE. G, Öberg CT, Hillgren JM, Elofsson M. Eur. J. Org. Chem. 2016; 426
• 5a Huang KS, Lin M, Wang YH. Chin. Chem. Lett. 1999; 10: 817
• 5b Yao CS, Lin M, Wang YH. Chin. J. Chem. 2004; 22: 1350
• 5c Takaya Y, Terashima K, Ito J, He YH, Tateoka M, Yamaguchi N, Niwa M. Tetrahedron 2005; 61: 10285
• 5d Wang GW, Wang HL, Capretto DA, Han Q, Hu RB, Yang SD. Tetrahedron 2012; 68: 5216
• 6 Li W, Li H, Luo Y, Yang Y, Wang N. Synlett 2010; 1247
• 7 Takaya Y, Yan KX, Terashima K, Ito J, Niwa M. Tetrahedron 2002; 58: 7259
• 8 Kim I, Choi J. Org. Biomol. Chem. 2009; 7: 2788
• 9 Wang XF, Yao CS. J. Asian Nat. Prod. Res. 2016; 18 in press; DOI: 10.1080/10286020.2015.1094464
• 10 Fischer J, Savage GP, Coster MJ. Org. Lett. 2011; 13: 3376
• 11a Rupprecht KM, Boger J, Hoogsteen K, Nachbar RB, Springer JP. J. Org. Chem. 1991; 56: 6180
• 11b Lau CK, Belanger PC, Dufresne C, Scheigetz J, Therien M, Fitzsimmons B, Young RN, Ford-Hutchinson AW, Riendeau D, Denis D, Guay J, Charleson S, Piechuta H, McFarlane CS, Chiu S.-HL, Chiu D, Eline RF, Alvaro G, Miwa J, Walsh L. J. Med. Chem. 1992; 35: 1299
• 12a Lanzilotti AE, Littell R, Fanshawe WJ, Mckenzie TC, Lovell FM. J. Org. Chem. 1979; 44: 4809
• 12b Kursanov DN, Parnes ZN, Loim NM. Synthesis 1974; 633
• 13 General Procedure for the Synthesis of Compound 12 t-BuOK (303 mg, 2.73 mmol) was added to a stirred solution of diethyl(4-methoxyphenyl)phosphonate (659 mg, 2.70 mmol) in THF (15 mL) at –40 °C. Then compound 4 (810 mg, 1.93 mmol) in THF (20 mL) was added, and the mixture was stirred at room temperature for 24 h. After the solvent was removed under reduced pressure, the mixture was diluted with EtOAc, washed with brine and water, dried over anhydrous Na₂SO₄, and concentrated in vacuo. The residue was purified by column chromatography over silica gel to afford compound 12. Analytical Data of Compound 12 Yield 98%, colorless oil; [α]_D ²⁵ 0 (c 0.07, MeOH). ¹H NMR (500 MHz, acetone-d ₆): δ = 7.31 (d, J = 8.7 Hz, 2 H), 7.26 (d, J = 8.7 Hz, 2 H), 7.04 (d, J = 16.4 Hz, 1 H), 6.94 (d, J = 8.7 Hz, 2 H), 6.83 (d, J = 8.7 Hz, 2 H), 6.82 (d, J = 2.4 Hz, 1 H), 6.79 (d, J = 16.4 Hz, 1 H), 6.48 (d, J = 2.4 Hz, 2 H), 6.46 (d, J = 2.4 Hz, 1 H), 6.39 (t, J = 2.4 Hz, 1 H), 5.57 (d, J = 5.5 Hz, 1 H), 4.66 (d, J = 5.5 Hz, 1 H), 3.85 (s, 3 H), 3.80 (s, 3 H), 3.77 (s, 3 H), 3.74 (s, 6 H). ¹³C NMR (125 MHz, acetone-d ₆): δ = 162.34 (4 C), 160.61, 160.54, 147.20, 136.26, 134.72, 130.89, 130.23, 128.61 (2 C), 127.87 (2 C), 123.97, 121.03, 114.86 (2 C), 114.79 (2 C), 106.79 (2 C), 102.95, 99.33, 95.77, 93.65, 57.19, 55.84, 55.62 (2 C), 55.57 (2 C). ESI-HRMS: m/z calcd for C₃₃H₃₃O₆Na: 547.2097; found: 547.2103.
• 14 General Procedure for the Synthesis of Compound 1 To a solution of compound 12 (200 mg, 0.38 mmol) in CH₂Cl₂ (20 mL), a solution of BBr₃ (4.6 mmol) in dichloromethane (20 mL) was added at –50 °C. The mixture was warmed up to –20 °C and stirred for 4 h. After stirred overnight at 5 °C, MeOH (5 mL) was added at –50 °C to quench the reaction. The solution was diluted with EtOAc, washed with water, dried over anhydrous Na₂SO₄, and evaporated under reduced pressure to afford a red residue, which was then purified through silica gel column chromatography and Sephadex LH-20 to afford compound 1. Analytical Cata of Compound 1 Yield 39%, reddish solid, mp 218.5–222.1 °C; [α]_D ²⁵ 0 (c 0.1, MeOH). ¹H NMR (500 MHz, CD₃OD): δ = 7.02 (d, J = 8.5 Hz, 2 H), 6.72 (d, J = 8.5 Hz, 2 H), 6.69 (d, J = 8.5 Hz, 2 H), 6.51 (d, J = 8.6 Hz, 2 H), 6.38 (d, J = 2.0 Hz, 1 H), 6.36 (d, J = 2.4 Hz, 1 H), 6.08 (d, J = 2.4 Hz, 1 H), 6.01 (d, J = 2.0 Hz, 1 H), 4.09 (d, J = 1.5 Hz, 1 H), 4.03 (s, 1 H), 3.56 (s, 1 H), 3.23 (s, 1 H). ¹³C NMR (125 MHz, CD₃OD): δ = 158.48 (s), 158.08 (s), 157.12 (s), 156.13, 156.11, 153.16 (s), 147.85 (s), 147.53 (s), 139.07 (s), 136.09 (s), 130.08 (2 C), 129.37 (2 C), 128.72 (s), 115.76 (2 C), 115.59 (2 C), 114.11 (s), 105.78, 104.32, 102.01, 101.92, 59.28, 50.95, 49.85, 47.65. ESI-HRMS: m/z calcd for C₂₈H₂₁O₆: 453.1338; found: 453.1351 [M – H]^–.