Piceatannol (3,3′,4,5′-tetrahydroxy-trans-stilbene, 2), an oxygenated analog of resveratrol (1), was synthesized. It is one of the naturally occurring polyphenolic stilbenoids contained in red wine, and possesses many kinds of beneficial effects such as anticancer activity. The trans-stilbene skeleton of 2 was constructed by Pd-catalyzed Suzuki-Miyaura cross coupling reaction of triflate 8 with (E)-alkenylboronoate 13. The key intermediate 13 was prepared diastereoselectively by acid-catalyzed hydroboration of pinacolborane 12 to alkyne 11.
TakaokaM. (1939) The phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.) I – Resveratrol. Nippon Kagaku Kaishi, 60, 1090–1100.
2.
RoldánA, PalaciosV, CaroI, PérezL. (2003) Resveratrol content of Palomino fino grapes: Influence of vintage and fungal infection. Journal of Agricultural and Food Chemistry, 51, 1464–1468.
3.
PatelKR, ScottE, BrownVA, GescherAJ, StewardWP, BrownK. (2011) Clinical trials of resveratrol. Annals of the New York Academy of Sciences, 1215, 161–169.
4.
MuriasM, HandlerN, ErkerT, PlebanK, EckerG, SaikoP, SzekeresT, JägerW. (2004) Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationship. Bioorganic and Medicinal Chemistry, 12, 5571–5578
BavarescoL, FregoniM, TrevisanM, MattiviF, VrhovsekU, FalchettiR. (2002) The occurrence of the stilbene piceatannol in grapes. Vitis, 41, 133–136.
7.
CunninghamJ, HaslamE, HaworthRD. (1963) The constitution of piceatannol. Journal of the Chemical Society, 2875–2883.
8.
PotterGA, PattersonLH, WanoghoE, PerryPJ, ButlerPC, IjazT, RupareliaK-C, LambJH, FarmerPB, StanleyLA, BurkeMD., (2002) The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. British Journal of Cancer, 86, 774–778.
AshikawaK, MajumdarS, BanerjeeS, BhartiAC, ShishodiaS, AggarwalBB. (2002) Piceatannol inhibits TNF-induced NF-κB activation and NF-κB-mediated gene expression through suppression of IκBα kinase and p65 phosphorylation. The Journal of Immunology, 169, 6490–6497.
11.
FlemingI, FisslthalerB, BusseR. (1995) Calcium signaling in endothelial cells involves activation of tyrosine kinases and leads to activation of mitogen-activated protein kinases. Circulation Research, 76, 522–529.
12.
ReimannE. (1970) Natürliche polyhydroxystilbene. Die synthese von oxyresveratrol, piceatannol und phapontigenin. Tetrahedron Letters, 11, 4051–4053
13.
AlonsoE, RamónDJ, YusM. (1997) Simple synthesis of 5-substituted resorcinols: A revisited family of interesting bioactive molecules. The Journal of Organic Chemistry, 62, 417–421
14.
HanSY, BangHB, LeeHS, HwangJW, ChoiDH, YangDM, JunJG. (2008) A new synthesis of stilbene natural product piceatannol. Bulletin of the Korean Chemical Society, 29, 1800–1802
15.
HanSY, LeeHS, ChoiDH, HwangJW, YangDM, JunJ-G. (2009) Efficient total synthesis of piceatannol via (E)-selective Wittig-Horner reaction. Synthetic Communications, 39, 1425–1432
16.
LeeHS, LeeBW, KimMR, JunJ-G. (2010) Syntheses of resveratrol and its hydroxylated derivatives as radical scavenger and tyrosinase inhibitor. Bulletin of the Korean Chemical Society, 31, 971–975
17.
SunH-Y, XiaoC-F, CaiY-C, ChenY, WeiW, LiuX-K, LvZ-L, ZouY. (2010) Efficient synthesis of natural polyphenolic stilbenes: Resveratrol, piceatannol and oxyresveratrol. Chemical and Pharmaceutical Bulletin, 58, 1492–1496.
18.
HoHE, AsaoN, YamamotoY, JinT. (2014) Carboxylic acid-catalyzed highly efficient and selective hydroboration of alkynes with pinacolborane. Organic Letters, 16, 4670–4673.
19.
We first prepared tetra-O-methylated 2 and attempted to remove the protective methyl groups of it by using AlI3 or BBr3 under the reported conditions [4a,11]. However, the reaction mixture was nasty, and it was difficult to obtain 2 in high yield and purity.
20.
NarayanS, RoushWR. (2004) Studies toward the total synthesis of angelmicin B (hibarimicin B): Synthesis of a model CD-D′ arylnaphthoquinone. Organic Letters, 6, 3789–3792.
21.
NegishiE, KingA-O, KlimaWL, PattersonW, SilveiraA.Jr. (1980) Conversion of methyl ketones into terminal acetylenes and (E)-trisubstituted olefins of terpenoid origin. The Journal of Organic Chemistry, 45, 2526–2528
SinghM, ArgadeNP. (2012) Palladium-catalyzed routes to geranylated or farnesylated phenolic stilbenes: Synthesis of pawhuskin C and schweinfurthin J. Synthesis, 44, 2895–2902.
