Synthesis 2018; 50(24): 4796-4808
DOI: 10.1055/s-0037-161114
feature
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Synthesis of 4-Amino-3-hydroxybenzopyran Flavanol Derivatives from Chalcones

Qiwen Gao
,
Lianyan L. Xu
,
Vincent P. Parise
,
Yash R. Mehta
,
Department of Chemistry, University of Illinois at Chicago, 845 W Taylor St., Chicago, IL 60607, USA   Email: aldrich@uic.edu
› Author Affiliations
Funding was provided by the UIC Department of Chemistry.
Further Information

Publication History

Received: 05 October 2018

Accepted after revision: 12 October 2018

Publication Date:
21 November 2018 (online)


Abstract

A concise method that is easily amenable for analogue synthesis has been developed to enantioselectively access 4-amino-3-hydroxybenzopyrans from chalcones. Epoxy alcohols were formed from chalcones through a Corey–Bakshi–Shibata reduction of the enone and subsequent Sharpless asymmetric epoxidation of the allylic alcohol. The epoxy alcohols were protected, regioselectively opened with various amines using catalytic europium(III) triflate, and the resulting free alcohols were orthogonally protected. Concomitant deprotection and intramolecular nucleophilic aromatic substitution provided the benzopyran core, which is poised to undergo additional reactions to provide a diverse chemical library with ideal properties for biological evaluation.

Supporting Information

 
  • References

  • 1 Aron PM, Kennedy JA. Mol. Nutr. Food Res. 2008; 52: 79
  • 2 Kinjo J, Nagao T, Tanaka T, Nonaka G.-I, Okawa M, Nohara T, Okab H. Biol. Pharm. Bull. 2002; 25: 1238
  • 3 Magcwebeba TU, Swart P, Swanevelder S, Joubert E, Gelderblom WC. A. Molecules 2016; 21: 1622
  • 4 Yoon H.-S, Kim JR, Park GY, Kim J.-E, Lee DH, Lee KW, Chung JH. J. Nutr. 2016; 146: 46
  • 5 Cheng T, Wang W, Li Q, Han X, Xing J, Qi C, Xi L, Wan J, Potts A, Guan F, Wang J. Free Radic. Biol. Med. 2016; 92: 15
  • 6 Rowley TJ, Bitner BF, Ray JD, Lathen DR, Smithson AT, Dallon BW, Plowman CJ, Bikman BT, Hansen JM, Dorenkott MR, Goodrich KM, Ye L, O’Keefe SF, Neilson AP, Tessem JS. J. Nutr. Biochem. 2017; 49: 30
  • 7 Cremonini E, Oteiza PI. Arch. Biochem. Biophys. 2018; 646: 55
  • 8 Cheng H, Xu N, Zhao W, Su J, Liang M, Xie Z, Wu X, Li Q. Mol. Nutr. Food Res. 2017; 61: 1700303
  • 9 Williamson G, Manach C. Am. J. Clin. Nutr. 2005; 81: 243S
  • 10 Hemmersbach S, Brauer SS, Hüwel S, Galla H.-J, Humpf H.-U. J. Agric. Food Chem. 2013; 61: 7932
  • 11 Ohno S, Nagasaka M, Kato K. US Patent US4334067A, 1982
  • 12 Nicolaou KC, Pfefferkorn JA, Roecker AJ, Cao GQ, Barluenga S, Mitchell HJ. J. Am. Chem. Soc. 2000; 122: 9939
  • 13 Helgren TR, Xu LL, Sotelo D, Mehta YR, Korkmaz MA, Pavlinov I, Aldrich LN. Chem. Eur. J. 2018; 24: 4509
  • 14 Corey EJ, Helal CJ. Angew. Chem. Int. Ed. 1998; 37: 1986
  • 15 Katsuki T, Sharpless KB. J. Am. Chem. Soc. 1980; 102: 5974
  • 16 Gao Y, Klunder JM, Hanson RM, Masamune H, Ko SY, Sharpless KB. J. Am. Chem. Soc. 1987; 109: 5765
  • 17 Keck GE, Andrus MB, Castellino S. J. Am. Chem. Soc. 1989; 111: 8136
  • 18 Overman LE, McCreedy RJ. Tetrahedron Lett. 1982; 23: 2355
  • 19 Shambayati S, Blake JF, Wierschke SG, Jorgensen WL, Schreiber SL. J. Am. Chem. Soc. 1990; 112: 697
  • 20 Chen X, Hortelano ER, Eliel EL, Frye SV. J. Am. Chem. Soc. 1992; 14: 1778
  • 21 Marcaurelle LA, Comer E, Dandapani S, Duvall JR, Gerard B, Kesavan S, Lee MD, Liu H, Lowe JT, Marie J.-C, Mulrooney CA, Pandya BA, Rowley A, Ryba TD, Suh B.-C, Wei J, Young DW, Akella LB, Ross NT, Zhang X.-L, Fass DM, Reis SA, Zhao W.-N, Haggarty SJ, Palmer M, Foley MA. J. Am. Chem. Soc. 2010; 132: 16962
  • 22 Pajouhesh H, Lenz GR. NeuroRx 2005; 2: 541