Concise Synthesis of Licochalcone A through Water-Accelerated [3,3]-Sigmatropic Rearrangement of an Aryl Prenyl Ether

Abstract

Claisen-Schmidt condensation of 4-(tetrahydropyran-2-yloxy)acetophenone with 2-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]benzaldehyde gave a THP-protected chalcone ether. Removal of the THP group under mild acidic conditions gave the corresponding chalcone ether, which underwent a water-accelerated Claisen rearrangement under microwave irradiation or heating in a sealed tube in aqueous ethanol to give a good yield of licochalcone A, which has diverse biological activities; no product of deprenylation or abnormal Claisen rearrangement was formed. The abnormal Claisen rearrangement of γ-substituted allyl aryl ethers is known to be a problem in [3,3]-sigmatropic rearrangement reaction; this, however, was not detected in our water-accelerated system.

Key words

rearrangements - condensation - natural products - licochalcone A

References

• 1a Saitoh T. Shibata S. Tetrahedron Lett.  1975,  4461 
• 1b Kajiyama K. Demizu S. Hiraga Y. Kinoshita K. Koyama K. Takahashi K. Tamura Y. Okada K. Kinoshita T. Phytochemistry  1992,  31:  3229 
• 1c Yoon G. Jung YD. Cheon SH. Chem. Pharm. Bull.  2005,  53:  694 
• 2 Kim J.-K. Shin EK. Park JH. Kim YH. Yoon Park JH. J. Mol. Med. (Heidelberg, Germany)  2010,  88:  829 
• 3 Mi-ich F. Miyadera H. Kobayashi T. Takamiya S. Waki S. Iwata S. Shibata S. Kita K. Ann. N. Y. Acad. Sci.  2005,  1056:  46 
• 4a Chen M. Zhai L. Christensen SB. Theander TG. Kharazmi A. Antimicrob. Agents Chemother.  2001,  45:  2023 
• 4b Chen M. Christensen SB. Blom J. Lemmich E. Nadelmann L. Fick K. Theander TG. Kharazmi A. Antimicrob. Agents Chemother.  1993,  37:  2550 
• 5 Haraguchi H. Ishikawa H. Mizutani K. Tamura Y. Kinoshita T. Bioorg. Med. Chem.  1998,  6:  339 
• 6 Fukai T. Satoh K. Nomura T. Sakagami H. Fitoterapia  2003,  74:  720 
• 7 Kwon H.-S. Park JH. Kim DH. Kim YH. Yoon Park JH. J. Mol. Med. (Heidelberg, Germany)  2008,  86:  1287 
• 8 Shibata S. Inoue H. Iwata S. Ma RD. Yu LJ. Ueyama H. Takayasu J. Hasegawa T. Takayasu J. Hasegawa T. Tokuda H. Nishino A. Nishino H. Iwasima A. Planta Med.  1991,  57:  221 
• 9 Park J.-H. Lim HJ. Lee K.-S. Lee S. Kwak H.-J. Cha J.-H. Park H.-Y. Biol. Pharm Bull.  2008,  31:  1996 
• 10 Kim YH. Kim J. Park H. Kim HP. Biol. Pharm. Bull.  2007,  30:  1450 
• 11 Sashidhara KV. Rosaiah JN. Kumar A. Synth. Commun.  2009,  39:  2288 ; and references cited therein
• 12a Islam A. Hossain MA. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1993,  32:  713 
• 12b Ren-Sheng X. Kung-Ling W. Shu FAJ. Chang-Gen W. Fu-Xiang X. Yu-Yuan X. Yi-Sheng G. Acta Chim. Sin. (Engl. Ed.)  1979,  37:  289 
• 12c Arsalan K, Christensen SB, Ming C, and Theander TG. inventors; US  5985935. 
• 13 Kromann H. Larsen M. Boesen T. Schønnig K. Nielsen SF. Eur. J. Med. Chem.  2004,  39:  993 
• 14a Castro AMM. Chem. Rev.  2004,  104:  2939 
• 14b Chanda A. Fokin VV. Chem. Rev.  2009,  109:  725 
• 14c Wipf P. Rodriguez S. Adv. Synth. Catal.  2002,  344:  434 
• 14d Nicolaou KC. Xu H. Wartmann M. Angew. Chem. Int. Ed.  2005,  44:  756 
• 14e Narayan S. Muldoon J. Fin MG. Fokin VV. Kolb HC. Sharpless KB. Angew. Chem. Int. Ed.  2005,  44:  3275 
• 15 In this [3,3]-sigmatropic rearrangement of aryl prenyl ether systems, the deprenylation product was unavoidably formed at high temperatures, see: Coombers CL. Moody CJ.
  J. Org. Chem.  2008,  73:  6758 
• 16 Polshettiwar V. Varma RS. Acc. Chem. Res.  2008,  41:  629 
• 17a Karanewsky DS. Kishi Y. J. Org. Chem.  1976,  41:  3026 
• 17b Fukuyama T. Li T. Peng G. Tetrahedron Lett.  1994,  35:  2145 
• 18a Mitsunobu O. Synthesis  1981,  1 
• 18b Lepore SD. He Y. J. Org. Chem.  2003,  68:  8261 
• 19 Khan SA. Krishnamurti M. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1983,  22:  276 

20

This compound has been reported to be an oily liquid (see ref. 12a), but we obtained it as a white solid.