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Synlett 2014; 25(08): 1116-1120
DOI: 10.1055/s-0033-1340989
letter
© Georg Thieme Verlag Stuttgart · New York

Towards the Synthesis of Platachromone B, a Bioactive Natural Prenylated (E)-2-Styrychromone

Frederico R. Baptista
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   eMail: artur.silva@ua.pt
,
Diana C. G. A. Pinto
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   eMail: artur.silva@ua.pt
,
Artur M. S. Silva*
Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   eMail: artur.silva@ua.pt
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Publikationsverlauf

Received: 20. Januar 2014

Accepted after revision: 19. Februar 2014

Publikationsdatum:
24. März 2014 (online)

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Abstract

Strategies towards the synthesis of the natural product platachromone B and related compounds have been investigated starting from commercially available phloroacetophenone. Direct C-prenylation of (E)-2-styryl-4H-chromen-4-ones was also studied. Methods for the synthesis of new (E)-5,7-dimethoxy-8-(3-methylbut-2-en-1-yl)-2-styryl-4H-chromen-4-ones and (E)-5-hydroxy-7-methoxy-6-(3-methylbut-2-en-1-yl)-2-styryl-4H-chromen-4-ones have also been established and are described for the first time.

Key words

natural products - drug discovery - prenylation - regioselectivity
 

  • References and Notes

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  • 11 (E)-2-Styrylchromones 11d,e were prepared according to the method described in references 6b and 6c.
  • 12 Selective 5-Demethylation of (E)-2-Styrylchromones 11d,e; General Procedure: AlCl3 (0.3334 g, 2.5 mmol) was added to a solution of the appropriate 2-styrylchromone 11d,e (0.25 mmol) in MeCN (20 mL). The solution was heated at reflux for approximately 24 hours. After this period, ice and water were added and the resulting solid was filtered. The crude product was purified by column chromatography using CH2Cl2 as eluent. After solvent evaporation and recrystallization from EtOH, (E)-5-hydroxy-7-methoxy-2-styryl-4H-chromen-4-ones 12a,b were obtained.
  • 13 Prenylation of (E)-5-Hydroxypolymethoxy-2-styrylchromones 12a,b; General Procedure: Prenyl bromide (0.234 mL, 2.04 mmol) was added to a solution of (E)-5-hydroxypolymethoxy-2-styrylchromones 12a,b (0.564 mmol) and K2CO3 (0.2340 g, 1.69 mmol) in acetone (50 mL). The reaction mixture was heated at reflux, under nitrogen, for 48 h. After this period, the solid K2CO3 was removed by filtration and the acetone was evaporated under reduced pressure. The resulting residue was purified by thick-layer chromatography using dichloromethane as eluent. After solvent evaporation and recrystallization of the residue from EtOH, (E)-5-hydroxy-7-methoxy-6-(3-methylbut-2-en-1-yl)-2-styryl-4H-chromen-4-ones 13a,b were obtained.
  • 14 (E)-5-Hydroxy-7-methoxy-6-(3-methylbut-2-en-1-yl)-2-styryl-4H-chromen-4-one (13b): Yield: 10%; yellow powder; mp 160–161 °C. 1H NMR (300.13 MHz, CDCl3): δ = 1.69 and 1.80 [s, 6 H, 6-CH2CH=C(CH 3)2], 3.36 [d, J = 7.1 Hz, 2 H, 6-CH 2CH=C(CH3)2], 3.94 (s, 3 H, 7-OCH 3), 6.16 (s, 1 H, H-3), 5.22 [t, J = 7.1 Hz, 1 H, 6-CH2CH=C(CH3)2], 6.49 (s, 1 H, H-8), 6.75 (d, J = 16.0 Hz, 1 H, H-α), 7.39–7.43 (m, 3 H, H-3′,4′,5′), 7.56–7.60 (m, 2 H, H-2′,6′), 7.58 (d, J = 16.0 Hz, 1 H, H-β), 12.82 (s, 1 H, 5-OH). 13C NMR (75.47 MHz, CDCl3): δ = 21.4 [6-CH2CH=C(CH3)2], 17.8 and 25.8 [6-CH2CH=C(CH3)2], 55.9 (7-OCH3), 89.6 (C-8), 105.7 (C-4a), 109.1 (C-3), 112.9 (C-6), 119.9 (C-α), 121.9 [6-CH2 CH=C(CH3)2], 127.7 (C-2′,6′), 129.0 (C3′,5′), 129.9 (C-4′), 132.0 [6-CH2CH=C(CH3)2], 134.9 (C-1′), 139.9 (C-β), 156.0 (C-8a), 158.4 (C-5), 161.8 (C-2), 163.3 (C-7), 182.5 (C-4). HRMS (ESI+): m/z calcd for C23H23O4 +: 363.1591; found: 363.1595.
  • 15 Demethylation of Methoxyprenyl-2-styrylchromones 11a–c; General Procedure: A solution of BBr3 in CH2Cl2 (1 M; 2.5 equiv for each methoxy group) was added to a solution of the appropriate 2-styrylchromones 11a–c (0.25 mmol) in freshly distilled CH2Cl2 (20 mL) and the mixture was cooled to –78 °C. The solution was then allowed to warm to r.t. and stirred for 8 to 11 days. After the appropriate period, H2O (40 mL) was added and the resulting solution was stirred at r.t. The mixture was then extracted with EtOAc (3 × 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure. The resulting residue was purified by column chromatography using CH2Cl2 as eluent. After solvent evaporation and recrystallization of the residue (EtOAc–light petroleum), (E)-5-hydroxy-8,8-dimethyl-2-styryl-9,10-dihydropyrano[2,3-f]chromen-4(8H)-ones 14a–c were obtained.
  • 16 (E)-5-Hydroxy-2-(4-hydroxystyryl)-8,8-dimethyl-9,10-dihydropyrano[2,3-f]chromen-4(8H) -one (14b): Yield: 10%; yellow powder; mp 261–262 °C. 1H NMR (300.13 MHz, acetone-d 6): δ = 1.41 [s, 6 H, 8-(CH 3)2], 1.96 (t, J = 6.8 Hz, 2 H, H-10), 2.98 (t, J = 6.8 Hz, 2 H, H-9), 6.13 (s, 1 H, H-3), 6.75 (s, 1 H, H-6), 6.95 (d, J = 8.8 Hz, 2 H, H-3′,5′), 6.99 (d, J = 16.4 Hz, 1 H, H-α), 7.54 (d, J = 16.4 Hz, 1 H, H-β), 7.64 (d, J = 8.8 Hz, 2 H, H-2′,6′), 8.97 (s, 1 H, 4′-OH), 12.75 (s, 1 H, 5-OH). 13C NMR (75.47 MHz, acetone-d 6): δ = 16.7 (C-9), 26.8 [8-(CH3)2], 32.2 (C-10), 76.8 (C-8), 100.2 (C-3), 100.9 (C-10a), 105.9 (C-4a), 108.4 (C-6), 116.8 (C-3′,5′), 117.7 (C-α), 127.7 (C-1′), 130.6 (C-2′,6′), 138.0 (C-β), 155.4 (C-10b), 160.3 (C-5), 160.6 (C-4′), 161.1 (C-2), 163.8 (C-7), 183.2 (C-4). HRMS (ESI+): m/z calcd for C22H21O5 +: 365.1383; found: 365.1381.
  • 17 2′-Hydroxy-4′,6′-dimethoxy-3′-(3-methylbut-2-en-1-yl)acetophenone (7a): Yield: 89%; white powder; mp 115–116 °C. 1H NMR (300.13 MHz, acetone-d 6): δ = 1.63 and 1.75 [s, 6 H, 3′-CH2CH=C(CH 3)2], 2.59 (s, 3 H, H-2), 3.24 [d, J = 5.0 Hz, 2 H, 3′-CH 2CH=C(CH3)2], 3.96 (s, 3 H, 4′-OCH 3), 3.99 (s, 3 H, 6′-OCH 3), 5.17 [t, J = 5.0 Hz, 1 H, 3′-CH2CH=C(CH3)2], 6.28 (s, 1 H, H-5′), 14.07 (s, 1 H, 2′-OH). 13C NMR (75.47 MHz, acetone-d 6): δ = 21.8 [3′-CH2CH=C(CH3)2], 17.7 and 25.8 [3′-CH2CH=C(CH3)2], 33.2 (C-2), 56.1 (4′,6′-OCH3), 87.5 (C-5′), 106.3 (C-1′), 109.6 (C-3′), 123.7 [3′-CH2 CH=C(CH3)2], 131.0 [3′-CH2CH=C(CH3)2], 163.0 (C-6′), 164.1 (C-2′), 164.4 (C-4′), 204.0 (C-1).
  • 18 For example, (E)-5,7-dimethoxy-8-(3-methylbut-2-en-1-yl)-2-styryl-4H-chromen-4-one (11a): Yield: 90%; yellow powder; mp 216–217 °C. 1H NMR (300.13 MHz, CDCl3): δ = 1.71 and 1.87 [s, 6 H, 6-CH2CH=C(CH 3)2], 3.57 [d, J = 6.8 Hz, 2 H, 6-CH 2CH=C(CH3)2], 3.96 (s, 3 H, 7-OCH 3), 3.99 (s, 3 H, 5-OCH 3), 66.18 (s, 1 H, H-3), 5.26 [t, J = 6.8 Hz, 1 H, 6-CH2CH=C(CH3)2], 6.41 (s, 1 H, H-6), 6.23 (d, J = 15.9 Hz, 1 H, H-α), 7.36–7.41 (m, 3 H, H-3′,4′,5′), 7.50 (d, J = 15.9 Hz, 1 H, H-β), 7.55 (d, J = 7.2 Hz, 2 H, H-2′,6′). 13C NMR (75.47 MHz, CDCl3): δ = 22.0 [6-CH2CH=C(CH3)2], 18.1 and 25.8 [6-CH2CH=C(CH3)2], 55.8 (7-OCH3), 56.4 (5-OCH3), 91.5 (C-6), 109.1 (C-4a), 109.9 (C-8), 111.7 (C-3), 120.5 (C-α), 122.4 [8-CH2 CH=C(CH3)2], 127.5 (C-2′,6′), 129.0 (C3′,5′), 129.5 (C-4′), 132.0 [8-CH2CH=C(CH3)2], 135.3 (C-1′), 135.8 (C-β), 156.2 (C-8a), 159.1 (C-2), 159.3 (C-5), 161.2 (C-7), 178.3 (C-4). HRMS (ESI+): m/z calcd for C24H24O4: 377.1747; found: 377.1744.