Highly regioselective dehexanoylation in fully hexanoylated flavonoids

Article abstract of DOI:10.1016/j.tetlet.2018.11.015

Highly selective removal of the 7-O-hexanoyl group in fully hexanoylated flavones, isoflavones, flavanone, and flavonol was achieved under mild conditions using K₂CO₃ in a 1:1 mixture of CH₃OH–CH₂Cl₂. The resulting 7-OH flavonoids are valuable intermediates for the synthesis of flavonoid 7-O-glycosides via phase-transfer-catalyzed (PTC) glycosylation.

Full text of DOI:10.1016/j.tetlet.2018.11.015

Accepted Manuscript
Highly Regioselective Dehexanoylation in Fully Hexanoylated Flavonoids
Zhiwei Zheng, Ziyi Han, Li Cai, Dandan Zhou, Bryson R. Chavis, Changsheng
Li, Qiang Sui, Kaiyuan Jiang, Qi Gao
PII:
S0040-4039(18)31331-5
https://doi.org/10.1016/j.tetlet.2018.11.015
TETL 50400
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
28 September 2018
31 October 2018
5 November 2018
Please cite this article as: Zheng, Z., Han, Z., Cai, L., Zhou, D., Chavis, B.R., Li, C., Sui, Q., Jiang, K., Gao, Q.,
Highly Regioselective Dehexanoylation in Fully Hexanoylated Flavonoids, Tetrahedron Letters (2018), doi: https://
doi.org/10.1016/j.tetlet.2018.11.015
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Highly Regioselective Dehexanoylation in Fully Hexanoylated Flavonoids
Zhiwei Zheng a,†, Ziyi Han a,†, Li Cai b,*, Dandan Zhou c, Bryson R. Chavis b,
Changsheng Li a, Qiang Sui a, Kaiyuan Jiang a and Qi Gao a,*
a China State Institute of Pharmaceutical Industry, 285 Gebaini Rd, Shanghai 201203, China
b
Department of Chemistry, University of South Carolina Lancaster, 476 Hubbard Dr,
Lancaster, South Carolina 29720, USA
c GenChim Testing (Shanghai) Co., Ltd, 526 3rd East Fute Rd, Waigaoqiao Pilot Free Trade
Zone, Shanghai 200131, China
† Z. Z. and Z. H. contributed equally to this work.
* Corresponding author:
Tel: +1 803-3137026 (L. Cai); +86 21-20572000 ext. 6045 (Q. Gao)
Email address: CAILI@mailbox.sc.edu (L. Cai); gao.qi@sipi.com.cn (Q. Gao)

Abstract: Highly selective removal of the 7-O-hexanoyl group in fully hexanoylated
flavones, isoflavones, flavanone, and flavonol was achieved under mild conditions using
K2CO3 in a 1:1 mixture of CH3OH–CH2Cl2. The resulting 7-OH flavonoids are valuable
intermediates for the synthesis of flavonoid 7-O-glycosides via phase-transfer-catalyzed
(PTC) glycosylation.
HexO
O
O
HO
O
O
(OHex)n
(OHex)n
selective
deacylation
Flavonoid 7-O-Glycosides
HexO
HexO
Keywords: Flavonoids; Dehexanoylation; Regioselectivity; Flavonoid glycosides; Phase
transfer.

Introduction
Flavonoids are widely distributed in plants [1], fulfilling many important
physiological functions. These compounds have also been shown to possess a broad spectrum
of biological activities, such as antioxidant [2-3], anti-proliferative, anti-tumor [4-6], anti-
microbial [7-8], estrogenic [9], acetylcholinesterase inhibitory [10], and anti-inflammatory
[11] activities, and therefore been widely used in cancer, cardiovascular disease,
neurodegenerative disorders, etc [12-14]. Unfortunately, issues remain unaddressed for
flavonoids in terms of their druggability because an understanding has existed for some time
that flavonoids tend to have low aqueous solubility and poor bioavailability. Many drugs
derived from natural products are glycosides having a sugar moiety linked to the aglycone
through an O-, or less commonly C-, glycosidic bond [15-16]. Therefore, glycosylation has
been used more and more frequently as a practical approach to improve the solubility and,
more importantly, the cellular uptake of flavonoids [17-21]. However, major challenges still
remain for the synthesis of flavonoid glycosides that could replace those from plant sources:
1) effective protecting strategies are required to discriminate the polyphenols present in the
flavonoid scaffold; 2) most flavonoids are not readily soluble in common organic solvents,
which in turn causes low nucleophilicity of the phenolic hydroxyl groups [22-24].
The most widely employed protecting groups for flavonoids are benzyl and acyl
groups. The introduction of benzyl-protecting groups in flavonoid derivatives usually
requires a reductive removal which not only is not fully compatible with the C2-C3 double
bond of many flavonoid structures but has the risk of the final products being strongly
absorbed to the charcoal when using Pd-C as the catalyst and a slow reaction [25-26]. While
a simple acetyl group that is commonly seen in carbohydrate chemistry seems ideal, it suffers
from limited lipophilicity and stability as well as poor regioselectivity during deprotection
[27]. Inspired by the work from Yu [28] and Botting [29] groups that use a hexanoyl ester-
based protection strategy, we successfully achieved a facile synthesis of 7-O-β-D-
glucopyranosyl-4’-O-α-L-rhamnopyranosyl apigenin starting from trihexanoyl apigenin (1a)
and through protective manipulation of the hydroxyls and subsequent glycosylation [30]. In
fact, the observed reactivity order of the hydroxyl groups of polyhydroxyflavones (Figure 1)
toward nucleophilic substitution, 7-OH > 4’-OH > 5-OH, has been well documented before

[31-32]. In our current work, we further investigate the preferential reactivity of the 7-OH in
the selective deacylation process and explore the substrate scope for its application on various
peracylated flavonoids, aiming to provide an advantage over previous methods that use the
foul-smelling thiophenol and achieve a facile route for various flavonoid 7-O-glycosides.
3'
OH
2'
4'
B
8
HO
O
C
5'
1'
7
6
2
3
6'
A
4
5
OH
O
apigenin
Figure 1. Structural formula of the model flavonoid skeleton, apigenin, showing rings A, B
and C and the numbering.
Table 1. Reaction condition screening for the regioselective deprotection of the 7-O-
hexanoyl group of apigenin (Hex = hexanoyl).
OHex
OHex
HexO
O
HO
O
base/solvent
temp. time (h)
HexO
O
HexO
O
1a
1b
Entry Base (0.5 eq.) Reaction time (h)
Solvent
Temperature (℃) Yield (%)
1
2
3
4
5
6
7
8
NaOH
NaOH
NaOH
KOH
24
18
8
CH3CN
MeOH
25
0
NR
28
48
51
NR
45
68
92
CH3OH-CH2Cl2 (1:1)
Acetone
25
40
25
25
25
25
8
Et3N
24
12
8
DMF
K2CO3
K2CO3
K2CO3
Acetone
CH3OH-CH2Cl2 (3:1)
CH3OH-CH2Cl2 (1:1)
4
Results and Discussion

In the polyphenolic structure of flavonoids, the 7-hydroxyl group is known to be the
most acidic because of the electron-withdrawing inductive effect of the pyrone carbonyl
group at its para position. It therefore generates the most stable corresponding 7-phenolate
which lays the foundation for the regioselective removal of the most electrophilic 7-O-acyl
moiety [33-34]. Selective release of the 7-OH on the peracylated flavonoids had been
achieved more than a decade ago using PhSH and a base catalyst in N-methyl pyrolidinone
[28]. However, we decided to abandon this system because of the strict reaction conditions
and aromatic thiols of repulsive and penetrating odor. Since PhS– is the key reactive species
in the transesterification/deprotection process, we envisioned the RO– generated from a polar
protic solvent (i.e. an alcohol) by a base with suitable basicity a promising alternative.
Expectedly, in our model reaction with perhexanoylated apigenin (1a) (Table 1), both the
solvent system and base played crucial roles. For bases used, NaOH and KOH proved to be
too strong resulting in over-deprotection. A protic solvent component seems necessary as
acetonitrile or DMF did not yield any dehexanoylation in the presence of NaOH or
triethylamine. However, using a protic solvent (i.e. CH3OH) alone or as a major component
(i.e. CH3OH-CH2Cl2 (3:1)) caused the loss of or decreased selectivity. The optimal reaction
conditions, moderately basic K2CO3 (pKa of its conjugate acid = 10.25) in a 1:1 mixture of
CH3OH-CH2Cl2, could remove the 7-O-hexanoyl group with excellent selectivity (92%) – no
deprotection on the next reactive/electrophilic 4’-O position was observed. The reaction was
performed at room temperature and reaction time determined by TLC monitoring.
To demonstrate the advantages of using the hexanoyl ester protection, we also
employed tri-O-acetyl apigenin and used HPLC to monitor the progress of both deacetylation
and dehexanoylation under the optimized condition for comparison (Figure 2). As shown,
removal of the 7-O-hexanoyl was evidently much faster and cleaner with less byproduct(s):
1) at 30 min, >50% of the starting material tri-O-hexanoyl apigenin was converted to the
desired 7-OH product and the conversion rate reached over 80% at 2 h; 2) upon completion at
4 h, regioselective release of 7-OH was accomplished to ~95% in dehexanoylation with
minimum byproduct observed; in contrast, poor selectivity (<40%) was obtained from the
deacetylation with >50% of over-deprotected dihydroxyl and trihydroxyl byproducts. These
results indicated that the more lipophilic hexanoyl group is more amenable to selective

deprotection and could better facilitate the reactivity discrimination at the 7-O position.
Next, the substrate scope for the selective dehexanoylation was explored using
various types of flavonoids (Table 2, entry 2-7), including luteolin (2) and acacetin (4)
(flavones), naringenin (3, a flavanone), daidzein (5) and genistein (6) (isoflavones), and
quercetin (7, a flavonol). These commercially available flavonoids were first treated with
hexanoyl chloride in DMF to afford the perhexanoylated substrates (1a-7a) in good yields
(81-95%) after recrystallization from methanol. As shown in Table 2, highly selective
dehexanoylation on the 7-O position was observed in all substrates (79-95%), including
luteolin (2a) and quercetin (7a) that contain 5,7,3’4’-O-tetrahexanoyl and 3,5,7,3’4’-O-
pentahexanoyl groups respectively. Therefore the preferential reactivity of the 7-OH was
evidenced in all flavonoid structures used, yielding a broad substrate-scope strategy for fast
and efficient protection-selective deprotection of flavonoids.

Figure 2. HPLC monitoring the deacylation progress, deacetylation vs. dehexanoylation.

Table 2. Selective dehexanoylation of the perhexanoylated flavonoids.
Yiel
d
Entry
Substrate
Product
1
92%
2
83%
3
4
79%
95%
5
6
88%
93%
7
85%
The obtained 7-hydroxyl flavonoids (1b-7b) are key intermediates in the preparation
of flavonoid O-glycosides as they often bear the sugar moiety at the 7-hydroxy position. It
has been reported that among the over 500 flavone O-glycosides and over 100 isoflavone O-

glycosides recorded, the majority are 7-O-glycosides and among the over l000 flavonol
glycosides recorded, roughly 40% contain a 7-O-glycosidic linkage [28,35]. In order to
demonstrate the use of our newly synthesized 7-hydroxyl flavonoids for flavonoid O-
glycosides, we chose 7-hydroxyl apigenin (1b) and 7-hydroxyl acacetin (4b) and carried out
phase-transfer-catalyzed (PTC) glycosylation [32,36] under basic conditions with
benzoylated glucosyl bromide (8) respectively (Scheme 1). Subsequent full deacylation of the
coupling products (9a, 10a) with sodium methoxide in CH2Cl2/CH3OH afforded apigenin 7-
O-glucoside (9b, Ref. [37]) and acacetin 7-O-glucoside (10b, Ref. [38]) (Scheme 1, see
Supporting Information for the detailed procedure of synthesizing the glycosides). Apigenin
7-O-glucoside (apigetrin or cosmosiin, CAS: 578-74-5) can be found in dandelion coffee and
in Teucrium gnaphalodes and also in a number of food items. Notably, recent studies show
its antifungal activity and cytotoxic activity on colon cancer cells were more prominent
compared to apigenin aglycone [39]. Acacetin 7-O-glucoside (tilianin, CAS: 4291-60-5) is a
vasorelaxant agent with antihypertensive effect [40] and a potential anti-inflammatory agent
which inhibit inducible nitric oxide synthase (iNOS) expression and production of NO [41].
Recently, potent cardioprotective effects of tilianin in rats have also been reported [42].
OHex
OHex
OH
BzO
BzO
BzO
HO
HO
HO
O
O
O
O
O
HO
O
O
O
BzO
HO
BzO
BzO
BzO
O
HexO
HexO
O
HO
9b
O
BzO
1b
9a, 79%
Br
, 77%
(ii)
8
(i)
OMe
OMe
OMe
BzO
HO
O
O
BzO
HO
HO
O
O
O
O
O
BzO
HO
BzO
HO
HexO
O
HexO
10a
O
HO
10b
O
4b
, 72%
, 84%
Scheme 1. Synthesis of apigenin 7-O-glucoside and acacetin 7-O-glucoside. Reagents and
o
conditions: (i) Bu4N+Br‒, CHCl3/aq. K2CO3 (0.24 M) (v:v, 1:1), 40 C; (ii) CH3ONa,
CH2Cl2/CH3OH, rt.
Conclusion
In summary, we described here an efficient hexanoyl-based protection strategy for

flavonoids which represents a broad substrate-scope method for the preparation of 7-hydroxyl
flavonoids. Hexanoate derivatives are more amenable to selective deprotection than other
esters and the method involves mild conditions using potassium carbonate in methanol-
dichloromethane. The resulting partially protected flavonoids were suitable substrates for
glycosylation with glycosyl bromides and similar products have been shown to possess useful
pharmacological properties. Further applications for the synthesis of these bioactive
molecules are underway.
Experimental Section
1. General procedure for the synthesis of perhexanoylated flavonoid (1a-7a)
Flavonoid (1 (5.40 g, 0.02 mol), 2 (5.72 g, 0.02 mmol), 3 (5.45 g, 0.02 mmol), 4 (5.69
g, 0.02 mmol), 5 (5.08 g, 0.02 mmol), 6 (5.40 g, 0.02 mmol), or 7 (6.04 g, 0.02 mmol)) was
dissolved in DMF (50 mL); Et3N (for 4,5, 6.9 mL, 0.05 mol; for 1,3,6, 9.7 mL, 0.07 mol; for
2, 12.4 mL, 0.09 mol; for 7, 15.3 mL, 0.11 mol) and DMAP (240 mg, 2 mmol) were added.
The mixture was then cooled in an ice-bath, and hexanoyl chloride (for 4,5, 6.9 mL, 0.05
mol; for 1,3,6, 9.7 mL, 0.07 mol; for 2, 12.4 mL, 0.09 mol; for 7, 15.3 mL, 0.109 mol) was
added and the reaction was allowed to slowly rise to room temperature in 30 minutes and
stirred for an additional 4 h. After complete consumption of the flavonoid starting material as
shown by TLC, the reaction mixture was diluted with CH2Cl2 (100 mL) and washed with 1 M
HCl aqueous solution (100 mL), saturated aqueous NaHCO3 (100 mL × 2), brine (100 mL),
dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford the crude
product (oil/solid), which was further purified by crystallization (methanol). Compound 1a-
3a (1a, 9.8 g, 87%, Ref. [30]; 2a, 11.5 g, 85%; 3a, 10.4 g, 92%) were obtained as a light
yellow solid and 4a-7a (4a, 8.4 g, 87%; 5a, 8.6 g, 95%, Ref. [28]; 6a, 9.1 g, 81%, Ref. [43];
7a, 13.1 g, 83%) as a white solid. Analytical data and NMR spectra see Supporting
Information.
2. General procedure for the regioselective removal of the 7-O-hexanoyl (1b-7b)
Perhexanoylated flavonoid (1a (2.82 g, 5 mmol), 2a (3.39 g, 5 mmol), 3a (2.83 g, 5
mmol), 4a (2.40 g, 5 mmol), 5a (2.25 g, 5 mmol), 6a (2.82 g, 5 mmol), or 7a (3.96 g, 5
mmol)) was dissolved in CH3OH–CH2Cl2 (1:1, 40 mL) and K2CO3 (345 mg, 2.5 mmol) was
added slowly. The reaction was stirred at room temperature and monitored by TLC. After

complete consumption of the starting material, the reaction was cooled in an ice-bath and
quenched with freshly prepared 1 M HCl/MeOH solution to a pH value of 8. The mixture
was then concentrated under reduced pressure to give the crude product (yellow oil/solid).
Further purification by silica gel column chromatography afforded 1b, 2b, 4b
(toluene/EtOAc = 5:1) as a white solid (1b, 2.14 g, 92%, Ref. [30]; 2b, 2.41 g, 83%; 4b, 1.81
g, 95%); 3b, 5b-7b (CH2Cl2/acetone = 15:1 to 25:1) as a white solid (3b, 1.85 g, 79%; 5b,
1.55 g, 88%, Ref. [28]; 6b, 2.17 g, Ref. [43], 93%; 7b, 2.95 g, 85%). Analytical data and
NMR spectra see Supporting Information.
Acknowledgements: QG’s work was supported by the National Natural Science Foundation
of China (21602134), the Shanghai Science and Technology Committee (STCSM) Pujiang
Talent Program (16PJ1432700), and the Shanghai Science and Technology Innovation –
International Collaboration Fund (18430721800). LC would like to acknowledge the partial
financial support through an RISE grant from the Office of the Vice President for Research at
the University of South Carolina and an RPS grant from the Dean’s Office at the University
of South Carolina Lancaster.
Supplementary data: Supplementary data (full experimental details for the glycosides 9a,
1
9b, 10a, 10b, and characterization of compounds – analytical data and H and 13C NMR
spectra) associated with this article can be found, in the online version, at
https://doi.org/10.1016/j.tetlet.
References
[1] M.M. Cowan, Clin. Microbiol. Rev. 12 (1999) 564-582.
[2] T. Yokozawa, E. Dong, Z.W. Liu, M. Shimizu, Phytother. Res. 11 (1997) 446-449.
[3] C.A. Rice-Evans, Curr. Med. Chem. 8 (2001) 797-807.
[4] Y.-L. Hsu, P.-L. Kuo, C.-C. Lin, Biochem. Pharmacol. 67 (2004) 823-829.
[5] R.P. Singh, P. Agrawal, D. Yim, C. Agarwal, R. Agarwal, Carcinogenesis 26 (2005) 845-854.
[6] Y.-L. Hsu, P.-L. Kuo, C.-F. Liu, C.-C. Lin, Cancer Lett. 212 (2004) 53-60.
[7] E. Middleton, C. Kandaswami, T.C. Theoharides, Pharmacol. Rev. 52 (2000) 673-751.
[8] R.I. Brinkworth, M.J. Stoermer, D.P. Fairlie, Biochem. Biophys. Res. Commun. 188 (1992) 631-637.
[9] A.P.S. de Oliveira, J.F. de Sousa, M.A. da Silva, F. Hilário, F.A. Resende, M.S. de Camargo, W. Vilegas,
L.C.d. Santos, E.A. Varanda, Steroids 78 (2013) 1053-1063.

[10] J.-S. Choi, Y.-J. Choi, S.-H. Park, J.-S. Kang, Y.-H. Kang, J. Nutr. 134 (2004) 1013-1019.
[11] M. Serafini, I. Peluso, A. Raguzzini, Proc. Nutr. Soc. 69 (2010) 273-278.
[12] M. Singh, M. Kaur, O. Silakari, Eur. J. Med. Chem. 84 (2014) 206-239.
[13] R.W. Li, A.G. Theriault, K. Au, T.D. Douglas, A. Casaschi, E.M. Kurowska, R. Mukherjee, Life Sci. 79
(2006) 365-373.
[14] L. Guo, W.-R. Hu, J.-H. Lian, W. Ji, T. Deng, M. Qian, B.-Q. Gong, Eur. J. Pharmacol. 551 (2006) 80-86.
[15] H. Pellissier, Tetrahedron 60 (2004) 5123-5162.
[16] J.T. Zacharia, M. Hayashi, Carbohydr. Res. 348 (2012) 91-94.
[17] P.C. Hollman, J.H. de Vries, S.D. van Leeuwen, M.J. Mengelers, M.B. Katan, Am. J. Clin. Nutr. 62 (1995)
1276-1282.
[18] J.M. Gee, M.S. DuPont, M.J.C. Rhodes, I.T. Johnson, Free Radical Biol. Med. 25 (1998) 19-25.
[19] R.A. Walgren, J.-T. Lin, R.K.-H. Kinne, T. Walle, J. Pharmacol. Exp. Ther. 294 (2000) 837-843.
[20] S. Wolffram, M. Blöck, P. Ader, J. Nutr. 132 (2002) 630-635.
[21] N.C. Veitch, R.J. Grayer, Nat. Prod. Rep. 25 (2008) 555-611.
[22] M. Nógŕdi, Á. Szöllosy, Liebigs Ann. 1996 (1996) 1651-1652.
[23] N.-G. Li, Z.-H. Shi, Y.-P. Tang, J.-P. Yang, J.-A. Duan, Beilstein J. Org. Chem. 5 (2009) No. 60.
[24] C. Demetzos, A.-L.a. Skaltsounis, F.o. Tillequin, M. Koch, Carbohydr. Res. 207 (1990) 131-137.
[25] K. Ohmori, H. Ohrui, K. Suzuki, Tetrahedron Lett. 41 (2000) 5537-5541.
[26] M. Selepe, F. Van Heerden, Molecules 18 (2013) 4739.
[27] B. Ren, L. Cai, L.R. Zhang, Z.J. Yang, L.H. Zhang, Tetrahedron Lett. 46 (2005) 8083-8086.
[28] M. Li, X. Han, B. Yu, J. Org. Chem. 68 (2003) 6842-6845.
[29] N. Al-Maharik, N.P. Botting, Tetrahedron Lett. 47 (2006) 8703-8706.
[30] Q. Gao, G. Lian, F. Lin, Carbohydr. Res. 344 (2009) 511-515.
[31] W. Peng, Y. Li, C. Zhu, X. Han, B. Yu, Carbohydr. Res. 340 (2005) 1682-1688.
[32] M. Li, X. Han, B. Yu, Tetrahedron Lett. 43 (2002) 9467-9470.
[33] P.W. Needs, G. Williamson, Carbohydr. Res. 330 (2001) 511-515.
[34] J.-S. Shin, K.-S. Kim, M.-B. Kim, J.-H. Jeong, B.-K. Kim, Bioorg. Med. Chem. Lett. 9 (1999) 869-874.
[35] J.B. Harborne, H. Baxter, The Handbook of Natural Flavonoids, John Wiley & Son, Chichester, UK, 1999;
Vol. 1 and 2.
[36] M. Hongu, K. Saito, K. Tsujihara, Synth. Commun. 29 (1999) 2775-2781.
[37] K.-i. Oyama, T. Kondo, Tetrahedron 60 (2004) 2025-2034.
[38] P. Cao, P. Xie, X. Wang, J. Wang, J. Wei, W.-y. Kang, BMC Complementary Altern. Med. 17 (2017) 93.
[39] M. Smiljkovic, D. Stanisavljevic, D. Stojkovic, I. Petrovic, J. Marjanovic Vicentic, J. Popovic, S. Golic
Grdadolnik, D. Markovic, S. Sankovic-Babice, J. Glamoclija, M. Stevanovic, M. Sokovic, EXCLI J. 16 (2017)
795-807.
[40] O. Hernández-Abreu, P. Castillo-España, I. León-Rivera, M. Ibarra-Barajas, R. Villalobos-Molina, J.
González-Christen, J. Vergara-Galicia, S. Estrada-Soto, Biochem. Pharmacol. 78 (2009) 54-61.
[41] K.-H. Nam, J.-H. Choi, Y.-J. Seo, Y.-M. Lee, Y.-S. Won, M.-R. Lee, M.-N. Lee, J.-G. Park, Y.-M. Kim,
H.-C. Kim, C.-H. Lee, H.-K. Lee, S.-R. Oh, G.T. Oh, Exp. Mol. Med. 38 (2006) 445–452.
[42] X. Guo, W. Cao, J. Yao, Y. Yuan, Y. Hong, X. Wang, J. Xing, Mol. Med. Rep. 11 (2015) 2227-2233.
[43] Z. Wu, G. Lian, B. Yu, Z. Wang, Y. Zhao, W. Xiao, Chin. J. Chem. 28 (2010) 1725-1730.

Highlights
 A hexanoyl-based protection strategy for flavonoids with broad substrate scope.
 Highly regioselective deprotection afforded various 7-hydroxyl flavonoids.
 A comparison between dehexanoylation and deacetylation.
 Phase-transfer-catalyzed glycosylation resulted in flavonoid 7-O-glycosides.