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

Qiwen Gao; Lianyan L. Xu; Vincent P. Parise; Yash R. Mehta; Leslie N. Aldrich

doi:10.1055/s-0037-161114

Synthesis, Table of Contents

Synthesis 2018; 50(24): 4796-4808
DOI: 10.1055/s-0037-161114

feature

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

Qiwen Gao

,

Lianyan L. Xu

,

Vincent P. Parise

,

Yash R. Mehta

,

Leslie N. Aldrich *

Department of Chemistry, University of Illinois at Chicago, 845 W Taylor St., Chicago, IL 60607, USA Email: aldrich@uic.edu

› Author Affiliations

Abstract

All articles of this category

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.

Key words

natural products - stereoselective synthesis - medicinal chemistry - nucleophilic aromatic substitution - nitrogen - heterocycles

Full Text

References

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

Supplementary Material

Supporting Information