Total synthesis of mangiferin, homomangiferin, and neomangiferin

Article abstract of DOI:10.1039/c6ob01622g

Total synthesis of mangiferin, homomangiferin, and neomangiferin, three C-glycosyl xanthone natural products with a wide spectrum of pharmacological effects, has been achieved starting from 2,3,4,6-tetra-O-benzyl-α/β-d-glucopyranose. The key steps involve a stereoselective Lewis acid promoted C-glycosylation of protected phloroglucinol with tetrabenzylglucopyranosyl acetate and a highly regioselective base-induced cyclization for the construction of the core xanthone skeleton.

Full text of DOI:10.1039/c6ob01622g

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DOI: 10.1039/C6OB01622G
Journal Name
ARTICLE
Total Synthesis of Mangiferin, Homomangiferin, and
Neomangiferin
Xiong Wei,a Danlin Liang,a Qing Wang,a Xiangbao Meng*a and Zhongjun Li*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
Total synthesis of mangiferin, homomangiferin, and neomangiferin, three C‐glycosyl xanthone natural products with a wide
spectrum of pharmacological effects, have been achieved starting from 2,3,4,6‐tetra‐O‐benzyl‐α/β‐D‐glucopyranose. The
DOI: 10.1039/x0xx00000x
key steps involve
a stereoselective Lewis acid promoted C‐glycosylation of protected phloroglucinol with
www.rsc.org/
tetrabenzylglucopyranosyl acetate and a highly regioselective base‐induced cyclization for the construction of the core
xanthone skeleton.
yield and poor regioselectivety.11 Recently, our group reported
an efficient semisynthesis of neomangiferin from naturally
isolated mangiferin.12 Nevertheless, the total synthesis of this
molecule 3, which bears both O‐ and C‐glycosides, is still a
challenge.
Introduction
Aryl C‐glycosides represent a unique class of natural products
with C‐C glycosidic bonds in their core skeleton.1 Possessing
remarkable stability toward both enzymatic and chemical
hydrolysis,2 these compounds usually exhibit a range of
interesting biological properties and therefore are considered
favorably as drug candidates.3 Mangiferin (
1, Figure 1), a
representative C‐glycosyl xanthonoid, was originally isolated as
a colorant matter from the mango tree (Mangifera Indica L.) by
Wiechowski and co‐workers in 19084 and now has been found
in many angiosperm plants and ferns.5 Since its discovery,
mangiferin has been shown to possess a wide spectrum of
pharmacological activities, including antioxidant, antitumor,
antiinflammatory, antidiabetic, lipolytic, antimicrobial, and
antiallergic activities, and thus has been considered as a
promising lead compound.6 The structurally related
Figure 1. Structures of mangiferin (1), homomangiferin (2), neomangiferin (3) and the
key biosynthetic intermediate (4).
In this work, we have based our synthetic studies on the
biosynthetic pathway of mangiferin, in which benzophenone
4
acts as the key intermediate and the glucosylation takes place
just prior to the construction of the core xanthone skeleton.13
Herein, we provide our efficient synthetic approach to
xanthonoids homomangiferin (2) and neomangiferin (3
),7,8
typically coisolated with mangiferin but in a lesser amount, also
display good antidiabetic properties.9 In view of their impressive
biological profile, we decide to undertake the total synthesis of
these mangiferin xanthonoids.
mangiferin (
first total synthesis of neomangiferin (
1
) and homomangiferin (
2
3
), and we also report the
).
Mangiferin was first obtained in about 0.1% yield via Result and discussion
treatment of the aglycon 1,3,6,7‐tetrahydroxyxanthone with a
Retrosynthetic analysis of mangiferin xanthonoids
large excess of α‐D‐glucopyranosyl bromide in 1967.10 It was not
until 2010 when Yu and co‐workers accomplished the first total
synthesis of mangiferin, isomangiferin and homomangiferin,
utilizing a highly stereoselective C‐glycosylation between a
xanthone derivative and tetrabenzylglucopyranosyl N‐
phenyltrifluoro acetimidate, but with a relatively low overall
Retrosynthetically, we envisioned that the key C‐C glycosidic
linkage between sugar and aromatic aglycon could be fashioned
by a O‐C rearrangement glycosylation (in which the O‐glycoside
intermediates was formed initially and then followed by Fries‐
type rearrangement to give the ortho C‐glycoside) between
2,3,4,6‐tetrabenzylglucose
Lewis acid promoted Friedel‐Crafts type glycosylation between
and phloroglucinol derivative 7 15
Subsequent addition of aryl‐
5 , or by a
and benzaldehyde 6 14
a. The State Key Laboratory of Natural and Biomimetic Drugs, Department of
Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing
100191, P. R. China.
5
.
metal 10 to the C‐glycoside precursor 9, followed by benzylic
oxidation and selective deprotection would then provide the
corresponding benzophenone 11 16
, and the xanthone skeleton,
b. National Research Center for Carbohydrate Synthesis, Jiangxi Normal University,
Nanchang 330022, P. R. China.
Email: zjli@bjmu.edu.cn or xbmeng@bjmu.edu.cn
which is the basic structure of the desired natural products (1‐
†Electronic Supplementary Information (ESI) available: General procedures and
characterization data (1H and 13C NMR spectra). See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
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Organic & Biomolecular Chemistry
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ARTICLE
), would be eventually constructed via a base‐induced glycosyl acetate 5e 19
Journal Name
which was less reactive thaVinew5Abrtic5lecOn5lidne
3
,
/
/
,
cyclization.17 (Scheme 1)
was a more suitable partner for the C‐glycosylation reaction on
the contrary, and accordingly, by treating donor 5e with
trimethoxybenzene 7a (2 equiv) and TMSOTf (5 equiv) in a
mixture solvent of CH2Cl2/THF at 0 C for 1 h, the desired C‐aryl
precursor 8a was obtained in a high 84% yield, with the
DOI: 10.1039/C6OB01622G
Base-induced Cyclization
OPG OH
R1O
O
O
OH
GPO
O
OMOM
OMOM
HO
HO
HO
BnO
BnO
OR2
BnO
OH
OBn
OH
O
OPG O
11
Nucleophilic Addition
1 R1 = R2 = H, Mangiferin
2 R1 = Me; R2 = H, Homomangiferin
anomeric stereoselectivity remaining unchanged (Table 1, Entry
5).
3 R1 = H, R2
=
-Glc, Neomangiferin,
GPO
O
OPG
GPO
OPG
CHO
MOMO
M
OMOM
OMOM
BnO
BnO
BnO
BnO
Table 1. Optimization of the C‐glycosylation reaction
O
BnO
+
BnO
OBn
OBn
OPG
OPG
10
8
9
Friedel-Crafts
Glycosylation
O-C Rearrangement
Glycosylation
GPO
OPG
GPO
OPG
CHO
BnO
BnO
BnO
O
5
OH
+
+
OBn
OPG
OH
6
5
7
Entry
Donor
5a
5b
5c
5d
Promoter
T (C)
0
rt
‐30
rt
0
Resulta
Scheme 1. Retrosynthetic analysis of mangiferin xanthonoids.
1
2
3
4
5d
BF3∙Et2O (2 eq)
BF3∙Et2O (1 eq)
TMSOTf (1 eq)
TMSOTf (2 eq)
TMSOTf (5 eq)
Complex
60%b
Total synthesis of homomangiferin
c
complex
84%b
Our studies commenced by focusing on obtaining access to C‐
glycoside precursor (Scheme 2). At the outset, a O‐C
rearrangement glycosylation using glycosyl fluoride 5a
(fluorinated from ) as the donor was attempted, expecting to
introduce the sugar moiety directly onto the aromatic ring of
benzaldehyde derivative 6a 14
However, due to the electron
5e
9
aIsolated yields were obtained using 2‐3 equiv of 7a. bSingle β‐anomer.
cInseparable mixture of α/β diastereomers. dReaction was conducted in 2:1
DCM/THF.
5
.
The subsequent introduction of aldehyde moiety onto the
aromatic ring was achieved successfully under the general
Vilsmeier‐formylation condition (DMF, POCl3, rt),20 affording
glycosyl benzaldehyde 9b as a pair of rotamers21 (observed by
1H NMR and 13C NMR) in 87% yield. Nevertheless, attempted
Friedel‐Crafts acylation employing acetyl chloride/AlCl3 or
acetic anhydride/TFA all led to substrate decomposition, likely
due to the sensitive nature of benzyl ether protecting groups to
acidic conditions.19 Therefore, it was not feasible to directly
construct glycosyl benzophenone by Friedel‐Crafts acylation
with benzoyl chloride derivative.
deficiency of acceptor 6a, coupling between 5a and 6a gave only
low yields of the desired C‐glycoside product 9a, regardless of
the promoters, solvents and conditions we used. Thus, to
remove the electron withdrawing effect of aldehyde group, a
Friedel‐Crafts type glycosylation18 our group reported before
was utilized instead. As anticipated, the glycosyl
trifluoroacetate 5b, easily esterified from 5, reacted smoothly
with trimethoxybenzene 7a (2 equiv) in the presence of
BF3∙Et2O (1 equiv) as a Lewis acid promoter, providing C‐aryl
glycoside 8a as a single β‐anomer (H‐1: 4.12 ppm, d, J = 10.4 Hz)
in 60% yield.
Scheme 3. Synthesis of cyclization precursor 11a.
Scheme 2. C‐glycosylation of carbohydrate 5a and 5b.
With C‐glycoside 9b in hand, we set out to investigate the
construction of cyclization precursor 11a (Scheme 3). The
requisite bromobenzene 10a for this procedure was initially
fashioned from 1,2,4‐benzenetriol by methoxymethylation
(MOMCl, DIPEA) and bromination (NBS, DMF, rt). Lithiation of
To further improve the relatively low yield of the coupling
reaction, we performed a minor optimization study by varying
the leaving groups on the glycosyl donor, as well as the
corresponding promoters (Table 1). The results showed that,
2 | J. Name., 2012, 00, 1‐3
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10a with n‐BuLi under low temerature (‐40
ARTICLE

C), followed by demethylation of its 3‐O‐methyl derivative
2
. However, any
View Article Online
trapping the generated anion with 9b in THF gave rise to an attempted removal of the remaining methyl group on 2
DOI: 10.1039/C6OB0o16r2o2Gn
inseparable mixture of diastereomeric aryl alcohols 13a (86%).16 corresponding precursor 16a proved to be problematic, which
Subsequent oxidation of 13a with excess activated MnO2 in was also observed in Yu’s work.11 Therefore, to get rid of this
CH2Cl2 provided 14a smoothly, and deprotection of the MOM dilemma, other protecting groups for the starting material
7
ether with catalytic amount of p‐toluenesulfonic acid in were tested, and accordingly, tribenzylphloroglucinol 7b was
refluxing methanol finally produced benzophenone 11a in 93% prepared following previous literature for later use.24
yield for two steps.
BnO
O
OBn
BnO
OBn
BnO
BnO
BnO
TMSOTf
POCl3, DMF
Unfortunately, attempted cyclization of 11a with cesium
carbonate as a base in MeOH failed to give any desired
products.22 Instead, a large amount of unidentified byproducts
was obtained. The catechol structure in 11a was assumed to be
the culprit. Thus, to tackle this problem, selective reprotection
of 11a was conducted again with chloromethylmethyl ether and
N, N‐diisopropylethylamine, providing monophenol 15a (85%)
with the stabilizing hydrogen bond remaining intact (Scheme
4).23 To our delight, the following intramolecular cyclization
proceeded smoothly on 15a, leading to the major 2‐C‐glycoside
16a and the minor 4‐C‐glycoside 17a in 88% and 10% yield,
respectively. Thus, HMBC correlations between signal of the
5e
+
DCM/THF, 0 C
1h, 89%
rt, 12h, 85%
OBn
8b
OBn
OBn
7b
OBn OMOM
BnO
OBn
CHO
10a
1)
, n-BuLi, THF
BnO
OMOM
BnO
BnO
BnO
BnO
BnO
BnO
-40 C, 2h
O
O
,
2) MnO2, DCM 40 C
72% for two steps
OMOM
OBn
OBn
OBn
OMe O
9c
14b
OBn OH
BnO
O
OR
OR
BnO
BnO
BnO
Cs2CO3
TsOH
MeOH, reflux, 0.5h
91%
MeOH, reflux
12h
OBn
OBn O
11b
, R = H
MOMCl, DIPEA
0 C, 2h, 84%
15b
, R = MOM
anomeric proton H‐1
ppm) were observed for 16a, and the signal of the anomeric
proton H‐1 with those of C‐3 (163.7 ppm), C‐4a (158.1 ppm)
were observed for 17a. Interestingly, due to the steric
hindrance of the sugar subunit to the ortho‐group, cyclization
was more favored to form the 2‐C‐glycoside product, therefore
adjustment of the base or solvent did not even affect the
resulted good regioselectivity.
 with those of C‐1 (160.7 ppm), C‐3 (163.8
R2
BnO
R1
O
OMOM
BnO
O
OH
OH
BnO
BnO
TsOH
O

MeOH, reflux
0.5h, 90%
OMOM
BnO
OBn
OBn O
OH
18b
O
16b
, R1
17b
=
-BnGlu, R2 = H, 92%
-BnGlu, 8%
, R1 = H, R2
=
HO
O
O
O
OH
OH
HO
HO
HO
Pd(OH)2/C, H2
EA/MeOH, rt, 2d
90%
OH
OH
1
,
Mangiferin
Scheme 5. Total synthesis of mangiferin.
The whole synthesis of mangiferin was accomplished in an
analogous manner (Scheme 5). Glycosylation of 7b with glycosyl
acetate 5e, followed by Vilsmeier formylation of 8b led to the
desired β‐C‐glycoside 9c in 76% overall yield. Subsequent
coupling with lithiated 10a and immediate oxidation of 13b
then gave rise to benzophenone 14b in 72% yield for two steps,
which was later converted into 15b by demethoxymethylation
and selective reprotection (76% for two steps). Gratefully, the
cyclization of 15b proceeded successfully to afford the major 2‐
C‐glycoside 16b and the minor 4‐C‐glycoside 17b in 92% and 8%
yield, respectively. For 16b, HMBC correlations between signal
Scheme 4. Completion of the synthesis of homomangiferin
Finally, removal of methoxymethyl ether under acidic
condition, followed by treatment with 1N BBr3 in
dichloromethane11, gave homomangiferin (
2) in 90% yield. Due
of the anomeric proton H‐1
(162.5 ppm) were observed, while for 17b, the signal of the
anomeric proton H‐1 with those of C‐3 (162.6 ppm), C‐4a (157.4
 with those of C‐1 (159.4 ppm), C‐3
to the restricted rotation of the glycosidic bond caused by 3‐O‐
methyl group, a pair of rotamers were observed both in the 1H

NMR and 13C NMR. The corresponding NMR signal (H‐1
:
ppm) were observed instead. Eventually, deprotection of
methoxymethyl and benzyl ether with toluenesulfonic acid and
4.61/4.56 ppm, d, J = 9.6 Hz ) for synthetic
that reported for the isolated natural product (H‐1
d, J = 9.6 Hz ),7 and the 3‐O‐CH3 group was assigned according
to the HMBC correlation between its signal (3.87 and 3.84 ppm)
with that of C‐3 (165.7 and 164.5 ppm).
2
was identical to
: 4.57 ppm,

catalytic hydrogenolysis afforded mangiferin
16b. And the analytical data of our synthetic mangiferin (H‐1
4.59 ppm, d, J = 9.6 Hz ) also matched that reported for the
natural compound (H‐1
: 4.59 ppm, d, J = 9.6 Hz).7,25
1 in 81% yield from

:

Total synthesis of mangiferin
Total synthesis of neomangiferin
Next, our attention focused on the synthesis of mangiferin
Originally, it was envisioned that could be achieved by further
1.
After completion of the total synthesis of mangiferin, we began
to explore the construction of neomangiferin (Scheme 6 and 7).
1
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J. Name., 2013, 00, 1‐3 | 3
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ARTICLE
Journal Name
BnO
O
O
OBn
25
BnO
BnO
BnO
Structurally, neomangiferin, bearing both O‐ and C‐glycosides,
is the 7‐O‐glucosyl derivative of mangiferin, which means, to
build this molecular, we first need to seek out an approach for
, TBAB, NaOH
AcO
View Article Online
OAc
24
DOI: 10.1039/C6OB01622G
OAc
OAc
CHCl3/H2O, 60 C
5h, 71%
O
O
OBn
OBn O
26
regioselective protection of 1, thereby providing an appropriate
1) Pd(OH)2/C, H2
MeOH/EA, rt, 2d
AcO
O
O
OAc
AcO
AcO
AcO
AcO
Na/MeOH
rt, 2h, 93%
aglycon with free 7‐OH for the required glycosylation. In view of
simplicity, we assumed to complete this procedure by
introducing orthogonal protecting groups onto 11b, just before
the intramolecular cyclization.
OAc
OAc
OAc
2) Ac2O, Py, rt, 12h
85% for two steps
O
O
OAc
OAc O
27
HO
HO
O
OH
HO
AcO
AcO
AcO
O
O
OH
OH
OH
HO
HO
O
O
AcO
OH
Br
OH
O
25
3 Neoangiferin
,
Scheme 7. Completion of the synthesis of neomangiferin.
Conclusions
In summary, we have achieved the efficient total synthesis of
the glycosyl xanthonoids mangiferin, homomangiferin and
neomangiferin from tetrabenzylglucose
5, phloroglucinol
derivative 7a/b and bromobenzene derivative 10a. The whole
synthesis proceeded in 10 or 13 steps with 33%, 40% and 18%
overall yield, respectively, featuring a stereoselective Friedel‐
Crafts type of glycosylation and a regioselective base‐induced
cyclization. The high overall yield of the process, which was
based on the biosynthetic pathway, makes the method one of
the most practical alternatives for relevant structural
modification. Further studies toward the structure‐activity
relationship are currently underway.
Scheme 6. Synthesis of glycosyl accepter 24.
The most reactive hydroxyl group on 11b, which located para
to the carbonyl group, was selectively benzylated with 1.2 equiv
of benzyl bromide in the presence of potassium carbonate,
affording 19 in 83% yield. Afterwards, several diverse protecting
groups were used to protect the meta‐hydroxyl group, in order
to leave the ortho‐ hydroxyl group free for the following
cyclization (Scheme 6). As a result, neither MOM nor TBDPS
ether would be suitable in our study; for the former, the
deprotection of MOM would also destroy the 1‐benzyloxy
group, while for the latter, the TBDMS group could not stand
the cyclization condition. We ultimately found, however, that
the utilization of allyl ether (AllylBr, K2CO3, acetone)26 could
successfully lead to the desired orthogonal protection, and
meanwhile, by further addition of cesium carbonate and
methanol, the generated intermediate 22 could be converted
directly into cyclization product 23 in an excellent yield (95% for
two steps), with only trace of 4‐C‐glycoside detected. Gratefully,
the removal of allyl ether went smoothly with Pd(PPh3)4 and
NaBH4,27 and aglycon 24 was obtained in a good yield of 85%.
Experimental section
General Information
Unless otherwise noted, all the reagents were obtained from
commercial suppliers and used without further purification.
Melting points were uncorrected. Nuclear magnetic resonance
spectra (NMR spectra) were recorded using 400 MHz
1
equipments (400 MHz for H; 100 MHz for 13C). All spectra
obtained in CDCl3 were referenced to tetramethylsilane at 0.00
1
ppm for H spectra and 77.16 ppm for 13C spectra. Spectra
obtained in DMSO‐d6 were referenced to DMSO at 2.50 ppm for
1H spectra and 39.52 ppm for 13C spectra. The following
abbreviations are used for the multiplicities: s: singlet, d:
doublet, t: triplet, q: quartet, m: multiplet, br s: broad singlet,
br d: broad doublet. High resolution mass spectra (HRMS) data
were performed with an ionization mode of ESI (electron spray
ionization). Optical rotations were measured using sodium D
line. Analytical thin layer chromatography (TLC) was performed
on Silica gel 60 F254 precoated on aluminiumplates, with
detection by fluorescence and (or) by staining with 5%
concentrated sulfuric acid in ethanol. Flash column
chromatography was performed using Silica gel (230~400 mesh)
with solvents distilled prior to use.
Glycosylation of 24 with α‐D‐glucopyranosyl bromide 25
,
under the general phase‐transfer catalysis (PTC) conditions
(TBAB, 5% NaOH, CH2Cl2, reflux), gave rise to the expected 7‐O‐
β‐D‐glucoside 26 in 71% yield,12 which was then debenzylated
through catalytic hydrogenolysis and acylated with acetic
anhydride to afford xanthone 27 in 85% yield for two steps. At
last, the cleavage of acetate ester was conducted with sodium
methoxide in methanol, and neomangiferin 3 was thus afforded
in 93% yield, with its structure confirmed by 1D and 2D NMR.8
Experimental procedures and characterization of products
4 | J. Name., 2012, 00, 1‐3
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Journal Name
Mangiferin:
ARTICLE
1,3,6,7‐Tetrahydroxy‐2‐
C‐β‐D
‐
4.59 (d, J = 9.6 Hz, 1H), 4.04 (t, J = 9.0 Hz, 1H), 3.81 – 3.05 (m,
View Article Online
13
glucopyranosylxanthone (1). To a solution of 18b (50 mg, 0.057 11H, covered by the signal of H2O) ppmD;OI: C10.N10M39R/C(61O0B001M62H2zG,
mmol) in MeOH (2 mL) and DCM (2 mL) was added 10% DMSO‐d6) δ 179.2, 164.2, 161.7, 156.5, 155.0, 152.8, 143.7,
Pd(OH)2/C (20 mg). After being stirred under 1 atm of H2 for 2 d 112.0, 110.5, 107.9, 103.4, 102.1, 101.5, 93.8, 81.7, 79.0, 77.3,
at room temperature, the suspension was filtrated through 75.9, 73.4, 73.3, 70.7, 70.4, 69.7, 61.6, 60.7 ppm; HRMS (ESI‐FT‐
Celite to remove the solid catalyst. The filtrate was ICR) m/z calcd for C25H29O16 [M + H]+ 585.1450, found 585.1447.
concentrated in vacuo, and the residue was purified by column 2,3,4,6‐Tetra‐
chromatography on Sephadex LH‐20 (CHCl3‐MeOH, 1:1) to a solution of
afford mangiferin (22 mg, 90%) as a yellow solid: mp over mL) was added acetic anhydride (20 mL) at room temperature.
O
‐benzyl‐α/β‐D‐glucopyranosyl acetate (5e). To
5
(15.5 g, 28.7 mmol) in anhydrous pyridine (100
1
250 °C (decomp.); 1H NMR (400 MHz, DMSO‐d6) δ 13.75 (s, 1H), After being stirred overnight, the reaction mixture was
10.53 (br s, 3H), 7.38 (s, 1H), 6.86 (s, 1H), 6.37 (s, 1H), 4.86 (br s, quenched with methanol, and evaporated in vacuo. The residue
2H), 4.59 (d, J = 9.6 Hz, 2H), 4.48 (br s, 1H), 4.04 (t, J = 8.8 Hz, was dissolved in DCM and washed with 1N HCl (aq), saturated
1H), 3.69 (d, J = 11.2 Hz, 1H), 3.40 (dd, J = 11.2, 5.6 Hz, 1H), 3.24 NaHCO3 (aq) and brine, and the combined organic layers were
– 3.03 (m, 3H) ppm; 13C NMR (100 MHz, DMSO‐d6) δ 179.4, dried over Na2SO4, concentrated, and purified by flash column
164.1, 162.1, 156.6, 154.2, 151.1, 143.9, 112.1, 108.4, 107.7, chromatography (PE‐EtOAc, 5:1) to afford 5e (16.5 g, 99%) as a
103.0, 101.7, 93.8, 81.7, 79.3, 73.5, 70.9, 70.7, 61.8 ppm; HRMS colorless syrup: 1H NMR (400 MHz, CDCl3) δ 7.37 – 7.17 (m, 18H),
(ESI‐FT‐ICR) m/z calcd for C19H19O11 [M + H]+ 423.0922, found 7.17 – 7.08 (m, 2H), 6.39 (d, J = 3.6 Hz, 0.8H), 5.64 (d, J = 8.0 Hz,
423.0930.
0.2H), 5.02 – 4.38 (m, 8H), 3.96 (t, J = 9.2 Hz, 0.8H), 3.92 – 3.85
Homomangiferin
：
1,6,7‐Trihydroxy‐2‐
C
‐β‐
D
‐glucopyranosyl‐ (m, 0.8H), 3.80 – 3.51 (m, 4.4H), 2.06 (s, 2.4H), 1.97 (s, 0.6H)
3‐O‐methylxanthone (2). To a solution of 16a (20 mg, 0.02 ppm; 13C NMR (100 MHz, CDCl3) δ 169.1/169.0, 138.5/138.3,
mmol) in MeOH (1 mL) was added catalytic amount of p‐ 138.0/138.0 137.8 /137.7, 137.5, 128.3, 128.2, 128.0, 127.8,
toluenesulfonic acid (0.5 mg). After being stirred for 0.5 h at 127.7, 127.6, 127.6, 127.5, 127.5, 93.9/89.8, 84.6/81.5,
80 °C, the reaction mixture was cooled to rt and evaporated 80.9/78.8, 77.1/76.8, 75.5/75.3, 75.1/74.8, 74.8, 73.3/73.3,
under reduced pressure. The residue was diluted with DCM, and 73.0, 72.7, 68.0, 20.9/20.8 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for
then washed with saturated NaHCO3 (aq) and brine, dried over C36H42NO7 [M + NH4]+ 600.2956, found 600.2972.
Na2SO4, and concentrated in vacuo to give the crude 1,3,5‐Tri‐O‐methyl‐2‐C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
intermediate 18a. The obtained 18a was pre‐treated to dryness glucopyranosyl)benzene (8a). Donor 5e (4.11 g, 7.05 mmol) and
and dissolved in anhydrous DCM (1 mL) under atmosphere of acceptor 7a (2.37 g, 14.09 mmol) were pre‐treated to dryness
nitrogen. After being cooled to ‐40 °C, BBr3 (1N in CH2Cl2, 1 mL) and dissolved in anhydrous DCM/THF (26 mL/13 mL) under
was added dropwise with an injector, and the reaction mixture atmosphere of nitrogen. After being cooled to 0 °C, TMSOTf (6.4
was stirred for 0.5 h before warming to room temperature. mL, 0.44 mmol) was added dropwise with an injector, and the
Another 3 h later, appropriate amount of water was added in to mixture was allowed to stir for 1 h before quenching with Et3N.
quench the reaction, and the whole mixture was evaporated The residue was diluted with DCM and washed with saturated
under reduced pressure. The residue was purified by column NaHCO3 (aq) and brine, and the combined organic layers were
chromatography on Sephadex LH‐20 (CHCl3‐MeOH, 1:1) to dried over Na2SO4, concentrated, and purified by flash column
afford homomangiferin
2 (9 mg, 90%) as a yellow solid, with chromatography (PE‐EtOAc, 5:1) to afford 8a (4.10 g, 84%) as a
rotamers observed by H NMR and 13C NMR: mp over 250 °C colorless syrup: [α]2D5 = +16.0 (c = 1.0, CHCl3); 1H NMR (400 MHz,
1
1
(decomp.); H NMR (400 MHz, DMSO‐d6 + D2O) δ 7.39 (s, 1H), CDCl3) δ 7.39 – 7.11 (m, 18H), 6.96 – 6.89 (m, 2H), 6.12 (dd, J =
6.90 (s, 1H), 6.62 (s, 0.5H), 6.61 (s, 0.5H), 4.58 (dd, J = 16.8, 10.0 24.0, 2.0 Hz, 2H), 5.00 – 4.85 (m, 4H), 4.75 (dd, J = 15.2, 11.6 Hz,
Hz, 1H), 4.17 (t, J = 9.2 Hz, 0.5H), 3.97 (t, J = 9.2 Hz, 0.5H), 3.87 2H), 4.52 (dd, J = 11.2, 4.4 Hz, 2H), 4.39 (t, J = 9.2 Hz, 1H), 4.12
(s, 1.5H), 3.84 (s, 1.5H), 3.67 (d, J = 6.0 Hz, 1H), 3.41 – 3.29 (m, (d, J = 10.4 Hz, 1H), 3.94 – 3.83 (m, 2H), 3.82 – 3.71 (m, 8H), 3.68
1H), 3.23 – 3.02 (m, 3H) ppm; 13C NMR (100 MHz, DMSO‐d6+D2O) (s, 3H), 3.57 (dd, J = 9.6, 2.0 Hz, 1H) ppm; 13C NMR (100 MHz,
δ 179.7/179.4, 165.7/164.5, 161.3/160.6, 157.2/157.1, 154.4, CDCl3) δ 161.4, 160.9, 159.9, 139.0, 138.9, 138.6, 138.5, 128.4,
151.2, 144.1, 112.2, 108.6, 108.3, 102.9, 102.6/102.2, 91.0/90.2, 128.4, 128.2, 128.2, 128.1, 128.0, 128.0, 127.6, 127.4, 127.2,
82.0/81.8, 79.1, 73.1/72.9, 71.0, 70.5/69.9, 61.8, 56.8/56.5 ppm; 107.8, 91.8, 90.8, 87.6, 80.0, 79.7, 78.5, 75.8, 75.1, 74.5, 73.2,
HRMS (ESI‐FT‐ICR) m/z calcd for C20H21O11 [M + H]+ 437.1078, 72.7, 69.1, 56.1, 55.8, 55.3 ppm; HRMS (ESI‐FT‐ICR) m/z calcd
found 437.1080.
Neomangiferin: 1,3,6‐Trihydroxy‐2‐
for C43H50NO8 [M + NH4]+ 708.3531, found 708.3543.
1,3,5‐Tri‐ ‐benzyl‐2‐ ‐(2,3,4,6‐tetra‐ ‐benzyl‐β‐
C
‐β‐D
‐glucopyranosyl‐7‐
O‐
O
C
O
D‐
β‐D‐glucopyranosylxanthane (3). To a solution of 27 (20.0 mg, glucopyranosyl)benzene (8b). Glycoside 8b was prepared from
0.019 mmol) in methanol (2 mL) was added catalytic amount of 5e and 7b following a procedure similar to that for 8a. Donor 5e
sodium at room temperature. After being stirred for 2 h, the (321 mg, 0.55 mmol), acceptor 7b (655 mg, 1.65 mmol), and
reaction mixture was neutralized with DOWEX 50WX8‐400 resin TMSOTf (0.50 mL, 2.75 mmol). The crude product was purified
(H+ form), filtered, and evaporated in vacuo. The residue was by flash column chromatography (PE‐EtOAc, 5:1) to afford 8b
purified by column chromatography on Sephadex LH‐20 (CHCl3‐ (450 mg, 89%) as a colorless syrup: [α]2D5 = +8.0 (c = 1.0, CHCl3);
MeOH, 1:1) to afford neomangiferin
3
(18.5 mg, 93%) as a 1H NMR (400 MHz, CDCl3) δ 7.48 (m, 2H), 7.39 – 7.07 (m, 31H),
yellow solid: mp 226‐227 °C; 1H NMR (400 MHz, DMSO‐d6 + D2O) 6.93 (dd, J = 7.6, 1.6 Hz, 2H), 6.25 (s, 2H), 5.10 – 4.79 (m, 10H),
δ 7.70 (s, 1H), 6.96 (s, 1H), 6.41 (s, 1H), 4.91 (d, J = 7.2 Hz, 1H), 4.60 (dd, J = 11.2, 6.4 Hz, 2H), 4.48 (dd, J = 11.6, 3.2 Hz, 2H), 4.45
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– 4.37 (t, J = 9.2 Hz,, 1H), 4.17 (d, J = 11.2 Hz, 1H), 3.82 – 3.66 added NBS solution (12.7 g in 50 mL DMF, 71.2 mmol) dropwise
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(m, 4H), 3.60 – 3.50 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ at room temperature. After being sDtiOrrI:e1d0.1o03v9e/rCn6iOghB0t,162th2Ge
160.3, 160.1, 159.3, 139.2, 138.9, 138.6, 138.5, 137.3, 136.8, reaction mixture was quenched with water and then diluted
128.7, 128.6, 128.4, 128.4, 128.4, 128.3, 128.1, 128.1, 128.1, with DCM. The organic layer was washed with brine, dried over
128.0, 128.0, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, Na2SO4, concentrated, and purified by flash column
127.3, 127.2, 127.2, 109.5, 94.9, 94.3, 87.8, 79.8, 79.5, 78.4, chromatography (PE‐EtOAc, 6:1) to afford 10a (18.1 g, 80%) as
75.4, 75.1, 74.1, 73.5, 73.4, 71.4, 70.8, 70.2, 69.5 ppm; HRMS a redish‐brown liquid: 1H NMR (400 MHz, CDCl3) δ 7.34 (s, 1H),
(ESI‐FT‐ICR) m/z calcd for C61H59O8 [M + H]+ 919.4205, found 7.04 (s, 1H), 5.20 (s, 2H), 5.17 (s, 2H), 5.15 (s, 2H), 3.53 (s, 3H),
919.4203.
2,4,6‐Tri‐
3.51 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 149.0, 147.3,
O
‐methyl‐3‐
C‐(2,3,4,6‐tetra‐
O
‐benzyl‐β‐
D
‐
142.7, 121.5, 106.7, 104.5, 96.0, 95.8, 95.6, 56.2, 56.1, 56.0 ppm;
glucopyranosyl)benzaldehyde (9b). To a solution of glycoside HRMS (ESI‐FT‐ICR) m/z calcd for C12H18BrO6 [M + H]+ 337.0281,
8a (4.10 g, 5.90 mmol) in anhydrous DMF (30 mL) was added found 337.0291.
POCl3 (3.40 mL, 35.6 mmol) under a nitrogen atmosphere. The 2,4,6‐Trimethoxy‐3‐C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
reaction mixture was stirred overnight at room temperature, glucopyranosyl)‐2',4',5'‐trihydroxybenzophenone (11a). To a
and then an additional POCl3 (1.00 mL) was added for the solution of 14a (1.13 g, 1.16 mmol) in MeOH (20 mL) was added
complete consumption of substrate. After another 4 h, 1N catalytic amount of p‐toluenesulfonic acid (20 mg, 0.12 mmol).
NaOH (aq) was added carefully to quench the reaction, and the After being stirred for 0.5 h at 80 °C, the reaction mixture was
mixture was diluted with DCM, washed with saturated NaHCO3 cooled to rt and evaporated under reduced pressure. The
(aq), 1N HCl (aq) and brine. The combined organic layers were residue was diluted with DCM, and then washed with saturated
dried over Na2SO4, concentrated, and purified by flash column NaHCO3 (aq) and brine, dried over Na2SO4, concentrated, and
chromatography (PE‐EtOAc, 3:2) to afford 9b (3.7 g, 87%) as a purified by flash column chromatography (PE‐acetone, 2:1) to
yellow syrup, with rotamers observed by 1H NMR and 13C NMR: afford 11a (0.91 g, 93%) as a yellow solid, with rotamers
[α]2D5 = +24.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 10.28 observed by 1H NMR and 13C NMR: [α]2D5 = +20.0 (c = 1.0, CHCl3);
(s, 1H), 7.40 – 7.05 (m, 18H), 6.90 (m, 2H), 6.17 (s, 1H), 4.99 – 1H NMR (400 MHz, DMSO‐d6) δ 12.20 (s, 1H), 10.55 (br s, 1H),
4.45 (m, 8H), 4.44 – 4.29 (m, 1H), 4.19 (d, J = 11.2 Hz, 1H), 3.96 8.80 (br s, 1H), 7.44 – 7.12 (m, 18H), 7.12 – 6.84 (m, 2H), 6.74 –
– 3.68 (m, 13H), 3.57 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 6.52 (m, 2H), 6.36 (s, 1H), 4.92 – 4.69 (m, 3.5H), 4.65 – 4.29 (m,
187.8/187.7,
165.3/165.2,
164.3/163.9,
163.9/163.7, 5.5H), 4.27 – 4.03 (m, 1H), 3.86 (s, 3H), 3.80 – 3.47 (m, 11H) ppm;
197.4, 161.4/160.0,
139.0/138.8, 138.7/138.5, 138.5/138.4, 138.2/ 138.2, 128.5, 13C NMR (100 MHz, DMSO‐d6)
δ
128.4, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9, 127.9, 158.1/157.4, 157.3/157.1, 155.4, 138.9/138.8, 138.5 138.4,
127.7, 127.6, 127.6, 127.5, 127.5, 127.4, 127.3, 114.1/113.2, 138.2/138.0, 128.2, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7,
113.1/112.3, 91.9/90.8, 87.9/ 87.4, 80.7/79.9, 79.0/78.8, 127.6, 127.5, 127.4, 127.4, 117.3, 116.0/114.9, 113.1/112.9,
78.4/78.3, 75.9/75.5, 75.1/75.1, 74.8/74.5, 73.3/73.2, 72.3, 112.8/112.2, 102.8, 93.3, 86.8/86.08, 80.3, 78.8, 78.3/78.0,
69.5/69.1, 65.5/64.4, 56.1, 56.0, 55.6 ppm; HRMS (ESI‐FT‐ICR) 74.7/74.5, 74.1/74.1, 73.6/73.5, 72.9, 72.3/71.8, 69.1, 63.5,
m/z calcd for C44H47O9 [M + H]+ 719.3215, found 719.3240.
2,4,6‐Tri‐ ‐benzyl‐3‐ ‐(2,3,4,6‐tetra‐ ‐benzyl‐β‐
56.4, 56.1, 56.0 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for
C50H54NO12 [M + NH4]+ 860.3641, found 860.3631.
O
C
O
D
‐
glucopyranosyl)benzaldehyde (9c). Benzaldehyde 9c was 2,4,6‐Tribenzyloxy‐3‐
C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
prepared from 8b following a procedure similar to that for 9b glucopyranosyl)‐2',4',5'‐trihydroxybenzophenone
.
(11b).
Thus, treatment of 8b (3.09 g, 3.36 mmol) with POCl3 (3 mL) in Benzophenone 11b was prepared from 14b following a
DMF (30 mL), after purification by flash column procedure similar to that for 11a. Thus, treatment of 14b (1.61
chromatography (PE‐EtOAc, 5:1), gave 9c (2.70 g, 85%) as a light g, 1.33 mmol) with catalytic amount of p‐toluenesulfonic acid,
yellow syrup, with rotamers observed by 1H NMR and 13C NMR: after purification by flash column chromatography (PE‐acetone,
[α]2D5 = +8.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 10.47 (s, 2:1), gave 11b (1.31 g, 91%) as a yellow solid, with rotamers
0.7H), 10.35 (s, 0.3H), 7.57 – 7.04 (m, 33H), 6.96 – 6.84 (m, 2H), observed by 1H NMR and 13C NMR: [α]2D5 = +12.0 (c = 1.0, CHCl3);
6.30 (s, 0.3H), 6.27 (s, 0.7H), 5.42 – 4.77 (m, 10H), 4.63 – 4.17 1H NMR (400 MHz, DMSO‐d6) δ 12.17 (s, 1H), 10.50 (br s, 1H),
(m, 6H), 3.83 – 3.30 (m, 5H) ppm; 13C NMR (100 MHz, CDCl3) δ 8.81 (br s, 1H), 7.68 – 6.64 (m, 37H), 6.37 (s, 1H), 5.41 – 4.23 (m,
187.7/187.6,
164.1/163.4,
163.4/162.9,
162.6/162.1, 15H), 4.14 (s, 1H), 3.73 – 3.48 (m, 5H) ppm; 13C NMR (100 MHz,
138.9/138.8, 138.7/138.3, 138.3/ 138.2, 137.9/137.5, 136.8, DMSO‐d6) δ 197.4, 160.3, 158.4, 156.5, 155.6, 138.9, 138.7,
136.0, 135.84, 128.8, 128.8, 128.7, 128.6, 128.6, 128.5, 128.4, 138.3, 138.2, 138.0, 137.9, 136.9, 136.7, 136.6, 128.8, 128.7,
128.4, 128.3, 128.3, 128.3, 128.2, 128.2, 128.1, 128.1, 128.0, 128.6, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.1, 128.0,
128.0, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.4, 127.2, 127.9, 127.7, 127.6, 127.4, 127.3, 127.3, 116.1, 113.1, 102.9,
127.1, 127.0, 126.9, 115.0, 114.1, 113.2, 94.9/94.8, 87.9/87.6, 96.1, 86.8, 78.9, 78.2, 78.0, 74.5, 74.3, 73.7, 73.6, 72.7, 71.0,
80.3/79.4, 79.3/79.2, 78.7/78.5, 78.3/78.2, 75.4/75.3, 70.2, 70.1, 69.2 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for C68H63O12
75.1/75.0, 74.4/74.2, 73.7/73.5, 73.3/72.9, 71.0/70.9, [M + H]+ 1071.4314, found 1071.4306.
70.8/70.4, 69.4/69.2 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for 1,2,4‐Tris(methoxymethoxy)benzene (12). 1,2,4‐Benzenetriol
C62H59O9 [M + H]+ 947.4154, found 947.4165.
1‐Bromo‐2,4,5‐tris(methoxymethoxy)benzene (10a). To
(2.5 g, 20 mmol) and DIPEA (15.8 mL, 90 mmol) were dissolved
in DCM (100 mL) and cooled to 0 °C. Chloromethylmethyl ether
a
solution of benzene 12 (17.5 g, 67.8 mmol) in DMF (50 mL) was (8.6 mL, 90 mmol) was then added dropwise with an injector
6 | J. Name., 2012, 00, 1‐3
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over 0.5 h. After being warmed to room temperature and 13C NMR: [α]2D5 = +16.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3)
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stirred overnight, 2N NaOH (aq) (100 mL) was added, and the δ 7.51 (s, 0.7H), 7.42 – 6.88 (m, 35.3H),D6O.8I:110(.s1,0039.7/CH6)O, B60.716622(sG,
mixture was then extracted with large amount of DCM. The 0.3H), 6.27 (s, 0.3H), 6.25 (s, 0.7H), 5.30 – 5.08 (m, 2H), 5.02 –
combined organic layer was washed with water and brine, dried 4.29 (m, 19H), 4.24 (d, J = 11.2 Hz, 0.7H), 4.20 (d, J = 11.2 Hz,
over Na2SO4, concentrated, and purified by flash column 0.3H), 3.68 – 3.16 (m, 11H), 3.01 (s, 2H), 3.00 (s, 1H) ppm; 13
C
chromatography (PE‐EtOAc, 6:1) to afford 12 (3.3 g, 64%) as a NMR (100 MHz, CDCl3) δ 191.4/191.3, 160.1/159.3, 158.1/157.3,
light yellow liquid: 1H NMR (400 MHz, CDCl3) δ 7.06 – 7.01 (m, 157.2, 153.8/153.6, 152.2/152.2, 141.6/141.5, 139.1,
1H), 6.91 – 6.83 (m, 1H), 6.68 – 6.58 (m, 1H), 5.18 (s, 2H), 5.12 139.0/138.9, 138.4/138.4, 138.1/137.4, 136.8, 136.6/136.4,
(s, 2H), 5.07 (s, 2H), 3.48 (s, 6H), 3.43 (s, 3H) ppm; 13C NMR (100 128.7, 128.5, 128.5, 128.4, 128.4, 128.3, 128.3, 128.3, 128.2,
MHz, CDCl3) δ 152.8, 148.1, 142.0, 118.1, 109.0, 106.2, 96.0, 128.2, 128.1, 128.0, 128.0, 127.9, 127.9, 127.8, 127.7, 127.7,
95.2, 94.8, 55.9, 55.8, 55.6 ppm;HRMS (ESI‐FT‐ICR) m/z calcd for 127.6, 127.5, 127.5, 127.4, 127.3, 127.2, 127.1, 126.9/126.9,
C12H19O6 [M + H]+ 259.1176, found 259.1173.
2,4,6‐Trimethoxy‐3‐ ‐(2,3,4,6‐tetra‐ ‐benzyl‐β‐D‐
123.9/123.7,
121.6/120.9,
120.2/119.8,
115.0/114.1,
C
O
105.0/104.5, 96.2/96.1, 95.9/95.7, 95.4, 95.2/95.1, 87.8/87.4,
glucopyranosyl)‐2',4',5'‐tris(methoxymethoxy)benzophenone 80.3/79.4, 79.1/79.1, 78.4, 78.2/77.8, 75.4/75.2, 75.1/75.0,
(14a). Bromobenzene 10a (1.6 g, 4.75 mmol) was dissolved in 74.2, 74.1/74.0, 73.4/73.4, 73.2, 71.4/70.8, 70.5/70.5,
anhydrous THF (15 mL) and cooled to ‐40 °C under a nitrogen 69.6/69.4, 56.5, 56.3/56.2, 56.0/56.0 ppm; HRMS (ESI‐FT‐ICR)
atmosphere. A 2.5M solution of n‐BuLi (1.9 mL, 4.75 mmol) was m/z calcd for C74H75O15 [M + H]+ 1203.5101, found 1203.5090.
added dropwise and the solution was allowed to stir for 1h at ‐ 2,4,6‐Trimethoxy‐3‐
C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
40 °C. The obtained mixture was then added dropwise into a glucopyranosyl)‐2'‐hydroxy‐4',5'‐
solution of 9b (1.14 g in 15 mL THF, 1.58 mmol), which was pre‐ bis(methoxymethoxy)benzophenone (15a). To a solution of
cooled to ‐40 °C under atmosphere of nitrogen. After being 11a (100 mg, 0.12 mmol) in CH2Cl2 (1 mL) was added DIPEA (88
stirred for another 1 h, appropriate amount of saturated NH4Cl µl, 0.5 mmol) and MOMCl (38 µl, 0.5 mmol) in portions at 0 °C.
(aq) was added to quench the reaction, and the mixture was The mixture was stirred for 3 h at 0 °C, and then diluted with
then diluted with DCM. The organic layer was washed with DCM. The combined organic layer was washed with water and
brine, dried over Na2SO4, concentrated, and purified by flash brine, dried over Na2SO4, concentrated, and purified by flash
column chromatography (PE‐EtOAc, 1:1) to afford 13a (1.44 g, column chromatography (PE‐acetone, 4:1) to afford 15a (93 mg,
86%) as a yellow syrup. To a solution of 13a (1.28 g, 1.3 mmol) 85%) as a yellow solid, with rotamers observed by 1H NMR and
25
1
in anhydrous DCM (25 mL) was added activated MnO2 (2.28 g, 13C NMR: [α] D = +12.0 (c = 1.0, CHCl3); H NMR (400 MHz,
26.2 mmol) at room temperature. After being stirred for 36 h, DMSO‐d6) δ 12.22 (s, 1H), 7.37 – 7.10 (m, 18H), 7.03 – 6.80 (m,
the reaction mixture was filtrated through Celite to remove the 3H), 6.71 (s, 1H), 6.64 (s, 1H), 5.32 (d, J = 8.4 Hz, 2H), 4.90 – 4.32
solid oxidant, and the filtrate was concentrated in vacuo and (m, 11H), 4.26 – 3.98 (m, 1H), 3.86 (s, 3H), 3.80 – 3.48 (m, 11H),
purified directly by flash column chromatography (PE‐EtOAc, 3.39 (s, 3H), 3.19 (s, 3H) ppm; 13C NMR (100 MHz, DMSO‐d6) δ
2:1) to afford 14a (1.28 g, quant) as a yellow syrup, with 197.9/197.8,
161.8/160.4,
159.6/159.5,
158.4/157.6,
rotamers observed by 1H NMR and 13C NMR: [α]2D5 = +28.0 (c = 157.5/157.4, 155.5/155.5, 138.9/138.8, 138.6, 138.5,
1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 7.36 – 7.13 138.4/138.3, 138.2/138.1, 128.2, 128.0, 127.8, 127.7, 127.6,
(m, 18H), 7.06 – 6.95 (m, 2H), 6.89 (s, 1H), 6.29 (s, 1H), 5.29 – 127.6, 127.5, 127.4, 127.3, 122.0/ 121.5, 115.4/114.2,
5.06 (m, 3H), 5.02 – 4.33 (m, 12H), 4.24 (d, J = 10.8 Hz, 1H), 3.90 114.1/114.1, 113.3/112.3, 103.3, 96.0/95.9, 94.4, 93.2,
– 3.62 (m, 13H), 3.58 – 3.48 (m, 4H), 3.48 – 3.35 (s, 3H), 3.21 (s, 92.2/86.7, 86.0/80.4, 78.8/78.6, 78.3/78.0, 74.7/74.4,
3H) ppm; 13C NMR (100 MHz, CDCl3) δ 192.0/191.6, 161.2/160.2, 74.1/74.0, 73.5/73.3, 72.9/72.3, 72.2/71.7, 69.1/69.0, 63.6,
159.6/158.6, 158.2, 153.8/153.4, 152.5/152.2, 141.6/1415, 56.3/56.2, 56.1, 56.0/56.0, 55.5 ppm; HRMS (ESI‐FT‐ICR) m/z
139.1/138.8, 138.8/138.6, 138.4/138.4, 128.5, 128.4, 128.4, calcd for C54H59O14 [M + H]+ 931.3899, found 931.3932.
128.3, 128.2, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.7, 2,4,6‐Tribenzyloxy‐3‐
C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
127.7, 127.6, 127.5, 127.4, 124.2/123.3, 120.6/120.2, glucopyranosyl)‐2'‐hydroxy‐4',5'‐
120.2/120.1, 113.8/113.0, 105.7/104.7, 96.3/96.2, 96.0/95.5, bis(methoxymethoxy)benzophenone (15b). Benzophenone
95.2, 92.8/91.2, 87.9/87.2, 80.9/79.8, 79.4/78.8, 78.6/78.3, 15b was prepared from 11b following a procedure similar to
75.9/75.6, 75.1, 74.5/74.3, 73.8/73.3, 73.2/72.6, 69.6/69.2, that for 15a. Thus, treatment of 11b (1.02 g, 0.95 mmol) with
64.2/63.8, 56.6, 56.3, 56.2, 56.1, 56.1, 56.0, 56.0 ppm; HRMS DIPEA (695 µl, 3.98 mmol) and MOMCl (189 µl, 2.49 mmol) at
(ESI‐FT‐ICR) m/z calcd for C56H63O15 [M + H]+ 975.4162, found 0 °C, after purification by flash column chromatography (PE‐
975.4170.
acetone, 4:1), gave 15b (0.93 g, 84%) as a light yellow solid, with
2,4,6‐Tribenzyloxy‐3‐C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
rotamers observed by 1H NMR and 13C NMR: [α]2D5 = +36.0 (c =
glucopyranosyl)‐2',4',5'‐tris(methoxymethoxy)benzophenone 1.0, CHCl3); 1H NMR (400 MHz, DMSO‐d6) δ 12.12 (s, 1H), 7.61 –
(14b). Benzophenone 14b was prepared from 10a and 9c 7.37 (m, 2H), 7.36 – 7.01 (m, 32H), 6.99 – 6.87 (m, 3H), 6.74 (s,
following a procedure similar to that for 14a. Thus, treatment 0.7H), 6.72 (s, 0.3H), 5.44 – 5.07 (m, 6H), 4.99 (d, J = 9.6 Hz, 0.3H),
of 9c (2.60 g, 2.75 mmol) with organolithium reagent and 4.90 (d, J = 10.4 Hz, 0.7H), 4.84 – 4.23 (m, 12H), 4.17 (d, J = 11.2
activated MnO2, after purification by flash column Hz, 0.7H), 4.09 (d, J = 10.4 Hz, 0.3H), 3.73 – 3.43 (m, 5H), 3.42 (s,
chromatography (PE‐EtOAc, 3:1), gave 14b (2.38 g, 72% for two 2H), 3.39 (s, 1H), 3.13 (s, 2H), 3.00 (s, 1H) ppm; 13C NMR (100
steps) as a yellow solid, with rotamers observed by 1H NMR and MHz, DMSO‐d6) δ 197.50, 160.6/159.6, 159.5/159.4, 156.6,
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156.3, 155.6/155.3, 138.8/138.8, 138.7/ 138.7, 138.2, 138.1, following a procedure similar to that for 16a and 17a. Thus,
View Article Online
DOI: 10.1039/C6OB01622G
137.9/137.9, 137.2/136.7, 136.4, 136.4/136.3, 128.5, 128.4, treatment of 15b (52 mg, 0.045 mmol) with Cs2CO3 (44 mg,
128.3, 128.2, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.8, 0.135 mmol) at 80 °C in MeOH (5 mL), after purification by flash
127.7, 127.6, 127.5, 127.5, 127.4, 127.3, 127.2, 127.0, 121.5, column chromatography (PE‐EtOAc, 4:1), gave 16b (45 mg, 92%)
115.2/114.5, 114.3, 113.2, 103.3, 95.8/95.7, 94.3, 86.7/86.3, as a white solid and 17b (4 mg, 8%) as a yellow solid respectively,
79.9/78.8, 78.4/78.1, 77.8/77.6, 74.3/74.2, 74.1/73.9, 73.4, with rotamers observed by 1H NMR and 13C NMR. Data for 16b
:
73.2, 72.4, 70.8, 70.0, 69.0, 56.16, 55.54 ppm; HRMS (ESI‐FT‐ICR) [α]2D5 = +28.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.90 (s,
m/z calcd for C72H71O14 [M + H]+ 1159.4838, found 1159.4835.
1,3‐Di‐ ‐methyl‐2‐ ‐(2,3,4,6‐tetra‐ ‐benzyl‐β‐
glucopyranosyl)‐6,7‐di‐
1,3‐Di‐ ‐methyl‐4‐ ‐(2,3,4,6‐tetra‐
glucopyranosyl)‐6,7‐di‐ ‐methoxymethylxanthone (17a). To a CDCl3)
0.7H), 7.80 (s, 0.3H), 7.66 – 7.49 (m, 2H), 7.42 – 6.84 (m, 27H),
6.83 – 6.67 (m, 2H), 6.49 (s, 0.3H), 6.47 (s, 0.7H), 5.38 – 4.59 (m,
O
C
O
D‐
O
‐methoxymethylxanthone (16a) and 12H), 4.55 – 4.19 (m, 5H), 4.14 (d, J = 11.6 Hz, 0.7H), 4.08 (d, J =
‐benzyl‐β‐
11.6 Hz, 0.7H), 3.69 – 3.13 (m, 11H) ppm; 13C NMR (100 MHz,
173.7, 162.5/161.8, 160.6/159.4, 159.1/159.0,
O
C
O
D‐
O
δ
solution of 15a (53 mg, 0.06 mmol) in MeOH (5 mL) was added 152.8/152.7, 151.2/151.0, 144.2/144.1, 138.9/ 138.7, 138.6,
Cs2CO3 (20 mg, 0.06 mmol) at room temperature. After being 138.5/138.3, 138.2/138.1, 137.9/137.4, 135.7/135.7, 128.9,
warmed to 80 °C and stirred overnight, the reaction mixture was 128.6, 128.4, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9,
cooled to rt and evaporated under reduced pressure. The 127.9, 127.8, 127.7, 127.6, 127.6, 127.4, 127.4, 127.3, 127.2,
residue was dissolved in DCM and filtrated to remove the 127.1, 127.0, 126.9, 118.6/117.7, 117.0/116.9, 112.2/ 112.0,
undissolved substance, and the filtrate was concentrated and 110.9/110.1, 103.2/103.1, 97.2/96.8, 95.6/95.6, 95.0, 87.8/87.5,
purified directly by flash column chromatography (PE‐acetone, 80.3/79.3, 78.3/78.2, 75.2/75.0, 74.9/74.8, 74.3/74.0,
4:1) to afford 16a (45 mg, 88%) as a white solid and 17a (5 mg, 73.8/73.3, 73.2/73.0, 70.8/70.3, 69.5/69.0, 56.4/56.3,
10%) as a yellow solid respectively, with rotamers observed by 56.3/56.2 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for C65H63O13 [M +
1H NMR and 13C NMR. Data for 16a: [α]2D5 = +48.0 (c = 1.0, CHCl3); H]+ 1051.4263, found 1051.4265. Data for 17b: [α]2D5 = +24.0 (c
1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.38 – 7.00 (m, 19H), = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 0.6H), 7.96 (s,
6.92 – 6.77 (m, 2H), 6.58 (s, 1H), 5.42 – 5.24 (m, 4H), 5.01 – 4.83 0.4H), 7.67 – 7.53 (m, 2H), 7.49 – 6.89 (m, 27H), 6.88 – 6.61 (m,
(m, 4H), 4.75 – 4.32 (m, 5H), 4.17 (d, J = 11.2 Hz, 1H), 3.96 (s, 2H), 6.38 (s, 0.4H), 6.35 (s, 0.6H), 5.42 – 4.86 (m, 11H), 4.83 (d,
3H), 3.90 – 3.67 (m, 7H), 3.64 – 3.47 (m, 7H) ppm; 13C NMR (100 J = 10.8 Hz, 0.6H), 4.73 (d, J = 10.8 Hz, 0.4H), 4.68 – 4.22 (m, 5H),
MHz, CDCl3)
159.5/159.4,
δ
174.0/173.9, 163.8/162.8, 162.4/160.7, 4.16 (dd, J = 11.2, 3.2 Hz, 1H), 3.98 – 3.59 (m, 5H), 3.59 – 3.47
153.0/153.0, 151.5/151.4,
144.3/144.3, (m, 5H), 3.44 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ
162.6/161.6, 161.0/160.8, 158.1/157.4,
139.1/138.9, 138.8/138.6, 138.5/ 138.4, 138.3/138.2, 128.6, 175.0/174.9,
128.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.1, 128.0, 127.8, 152.9/152.9, 151.3/151.2, 144.3/144.3, 139.0/138.8, 138.7/
127.8, 127.7, 127.6, 127.5, 127.5, 127.4, 127.3, 118.3/117.5, 138.6, 138.4, 138.1/138.1, 136.5, 136.3/136.1, 128.9, 128.8,
117.2/117.1, 112.4, 110.7/110.0, 103.4/103.3, 96.3/95.9, 128.7, 128.6, 128.6, 128.5, 128.5, 128.4, 128.3, 128.3, 128.2,
95.3/95.1, 88.0/87.5, 80.9/79.9, 79.0/78.9, 78.49/ 78.4, 128.1, 128.1, 128.0, 127.9, 127.9, 127.8, 127.7, 127.6, 127.5,
76.0/75.6, 75.3/75.2, 75.0/74.4, 73.5/73.4, 73.2/72.5, 127.5, 127.4, 127.3, 127.2, 127.0, 127.0, 117.1/116.9, 112.4/
69.6/69.1, 64.5/63.5, 56.7/ 56.6, 56.5/56.5, 56.3/55.8 ppm; 112.2, 108.0/107.4, 107.4/107.3, 103.8/103.5, 96.0, 95.3/95.3,
HRMS (ESI‐FT‐ICR) m/z calcd for C53H55O13 [M + H]+ 899.3637, 95.0/94.8, 88.0/87.9, 79.8/79.6, 79.5/79.2, 78.6/78.5,
found 899.3623. Data for 17a: [α]2D5 = +24.0 (c = 1.0, CHCl3); 1H 76.0/75.6, 75.3/75.0, 74.5/74.4, 73.6/73.2, 73.0/72.8,
NMR (400 MHz, CDCl3) δ 7.94 (s, 0.5H), 7.93 (s, 0.5H), 7.42 – 6.90 71.3/71.1, 70.8, 69.5/69.1, 56.7/56.6, 56.5/56.5 ppm; HRMS
(m, 19H), 6.86 – 6.70 (m, 2H), 6.34 (s, 0.5H), 6.25 (s, 0.5H), 5.47 (ESI‐FT‐ICR) m/z calcd for C65H63O13 [M + H]+ 1051.4263, found
– 4.90 (m, 8H), 4.79 – 4.46 (m, 4H), 4.42 (t, J = 9.2 Hz, 0.5H), 4.31 1051.4265.
(t, J = 9.2 Hz, 0.5H), 4.21 (d, J = 11.2 Hz, 0.5H), 4.15 (d, J = 11.2 1,6,7‐Trihydroxy‐2‐
Hz, 0.5H), 4.03 (s, 1.5H), 4.00 (s, 1.5H), 3.96 – 3.60 (m, 8H), 3.58 glucopyranosyl)‐3‐
C
‐(2,3,4,6‐tetra‐
O‐benzyl‐β‐D‐
O‐benzylxanthone (18b). Glycosyl xanthone
– 3.40 (m, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 175.2/175.0, 18b was prepared from 16b following a procedure similar to
163.7/162.6, 162.4, 158.1/157.4, 153.0/152.9, 151.3/151.2, that for 11a. Thus, treatment of 16b (626 mg, 0.60 mmol) with
144.2, 138.9/138.8, 138.8/ 138.7, 138.6/138.6, 138.1/137.8, catalytic amount of p‐toluenesulfonic acid, after purification by
128.6, 128.6, 128.5, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, flash column chromatography (PE‐EtOAc, 1:1), gave 18b (466
127.9, 127.9, 127.9, 127.8, 127.5, 127.5, 127.5, 127.4, mg, 90%) as a yellow solid, with rotamers observed by 1H NMR
117.1/116.8,
112.6/112.4,
107.3/106.7,
106.5/106.4, and 13C NMR: [α]2D5 = +32.0 (c = 1.0, CHCl3); 1H NMR (400 MHz,
103.8/103.5, 96.1/95.3, 91.5/90.6, 88.0/87.9, 79.8/79.7, 79.6, CDCl3) δ 13.51 (s, 0.5H), 13.40 (s, 0.5H), 8.03 (br s, 1H), 7.42 –
78.6/78.6, 76.1/75.3, 75.2/74.7, 73.4/73.3, 72.8/72.5, 6.72 (m, 27H), 6.55 (s, 0.5H), 6.37 (s, 0.5H), 6.04 (s, 0.5H), 6.02
69.2/69.1, 56.7/ 56.6, 56.5/56.5, 56.4, 55.9 ppm; HRMS (ESI‐FT‐ (s, 0.5H), 5.08 – 4.63 (m, 6.5H), 4.60 – 4.10 (m, 5.5H), 3.80 – 3.47
ICR) m/z calcd for C53H55O13 [M + H]+ 899.3637, found 899.3625. (m, 4H), 3.32 (t, J = 8.8 Hz, 0.5H), 3.15 (t, J = 9.2 Hz, 0.5H) ppm;
1,3‐Di‐
glucopyranosyl)‐6,7‐di‐
1,3‐Di‐ ‐benzyl‐4‐ ‐(2,3,4,6‐tetra‐
glucopyranosyl)‐6,7‐di‐ ‐methoxymethylxanthone
O
‐benzyl‐2‐
C
‐(2,3,4,6‐tetra‐
O
‐benzyl‐β‐
D
‐
13C NMR (100 MHz, CDCl3) δ 179.3/179.1, 163.8/163.3,
157.7/157.5, 154.1/152.8, 151.7/151.4,
142.2/141.3, 138.7/ 138.6, 138.4/137.9, 137.8/137.8, 136.4,
O‐methoxymethylxanthone (16b) and 161.7/161.4,
O
C
O‐benzyl‐β‐
D
‐
O
(17b). 136.1/136.0, 128.7, 128.6, 128.5, 128.5, 128.5, 128.4, 128.4,
Glycosyl xanthone 16b and 17b were prepared from 15b 128.2, 128.1, 127.9, 127.9, 127.7, 127.3, 127.2, 113.0/112.6,
8 | J. Name., 2012, 00, 1‐3
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111.9/ 109.9, 106.2/106.2, 103.5/102.6, 102.4/102.3, 91.1/90.9, 69.9/69.7, 69.17, 65.08 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for
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87.8/87.3, 78.7/78.5, 78.4, 78.3/78.2, 75.5, 75.2/74.9, C71H65O11 [M + H]+ 1093.4521, found 109D3O.4I:51301.1.039/C6OB01622G
74.3/74.1, 73.7/73.5, 72.9/72.2, 70.9/70.8, 69.8/69.1 ppm. 1,3,6‐Tri‐
O‐benzyl‐2‐C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
HRMS (ESI‐FT‐ICR) m/z calcd for C54H49O11 [M + H]+ 873.3269, glucopyranosyl)‐7‐hydroxyxanthone (24). Glycosyl xanthone
found 873.3250.
2,4,4',6‐Tetrabenzyloxy‐3‐C‐(2,3,4,6‐tetra‐O‐benzyl‐β‐D‐
glucopyranosyl)‐2',5'‐hydroxybenzophenone (19). To
23 (707 mg, 0.65 mmol) was dissolved in anhydrous THF (10 mL)
at room temperature, and Pd(PPh3)4 (15 mg, 0.013 mmol) and
NaBH4 (49 mg, 1.29 mmol) were added successively. The
a
solution of 11b (50 mg, 0.047 mmol) in acetone (2 mL) was reaction mixture was stirred at rt for 1 h, and then diluted with
added K2CO3 (26 mg, 0.187 mmol) and BnBr (7 µL, 0.056 mmol) DCM. The organic layer was washed with 1N HCl (aq) and brine,
at room temperature. After being warmed to 60 °C and stirred dried over Na2SO4, concentrated, and purified by flash column
for 1 h, the reaction mixture was cooled to rt and filtrated to chromatography (PE‐EtOAc, 4:1) to afford 24 (580 mg, 85%) as
remove the solid reagent. The combined filtrate was a light yellow solid, with rotamers observed by 1H NMR and 13
C
concentrated in vacuo, and purified directly by flash column NMR: [α]2D5 = +24.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ
chromatography (PE‐acetone, 4:1) to afford 19 (45 mg, 83%) as 7.84 – 7.63 (m, 3H), 7.56 – 6.99 (m, 31H), 6.95 – 6.75 (m, 3H),
a yellow solid, with rotamers observed by 1H NMR and 13C NMR: 6.58 (s, 1H), 5.96 – 5.59 (m, 1H), 5.48 – 4.68 (m, 10H), 4.63 –
[α]2D5 = +24.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 12.48 4.31 (m, 5H), 4.29 – 4.09 (m, 1H), 3.80 – 3.60 (m, 3H), 3.60 –
(s, 0.7H), 12.35 (s, 0.3H), 7.53 – 6.85 (m, 42H), 6.69 – 6.27 (m, 3.24 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 173.9,
2H), 5.49 – 4.17 (m, 18H), 3.89 – 3.35 (m, 5H) ppm; 13C NMR 162.5/161.4,
(100 MHz, CDCl3) 198.8, 160.8/160.0, 159.2/159.0, 149.9/149.6, 143.3, 139.0/138.8, 138.7/138.5, 138.4/138.2,
160.5/159.4,
159.0/158.9,
152.0/151.6,
δ
157.8/156.7, 153.3/153.2, 139.1/139.0, 139.0, 138.4/138.3, 138.2/138.1, 138.0/137.6, 135.9, 135.4/135.3, 129.3, 128.7,
138.0/137.8, 136.7/136.4, 136.3/135.2, 128.9, 128.8, 128.7, 128.5, 128.5, 128.4, 128.4, 128.3, 128.3, 128.2, 128.1, 128.1,
128.6, 128.6, 128.6, 128.5, 128.4, 128.4, 128.3, 128.1, 128.1, 128.0, 128.0, 127.9, 127.8, 127.7, 127.5, 127.4, 127.4, 127.3,
128.0, 127.9, 127.83, 127.8, 127.7, 127.7, 127.5, 127.4, 127.3, 127.2, 127.0, 118.1/117.4, 116.7/116.3, 110.9/110.3,
127.2, 127.1, 127.0, 126.9, 117.9, 116.9, 116.2, 115.2, 114.7, 110.1/109.9, 99.63, 97.4/96.7, 87.7/87.6, 80.4, 79.2/79.1,
114.6/114.3, 100.6, 96.1, 87.9/87.6, 80.7, 79.6/79.3, 78.7, 78.5/78.3, 77.4/77.3, 75.2/75.0, 74.9, 74.3/74.1, 73.9/73.4,
78.3/78.2, 75.4, 75.1/75.0, 74.4/74.2, 73.6/73.5, 73.2, 71.5, 73.2/73.1, 71.3/71.2, 70.8/70.7, 69.2, 69.1 ppm; HRMS (ESI‐FT‐
71.2/71.0, 70.6, 69.4/69.2 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for ICR) m/z calcd for C68H61O11 [M + H]+ 1053.4208, found
C75H69O12 [M + H]+ 1161.4784, found 1161.4810.
1,3,6‐Tri‐ ‐benzyl‐2‐ ‐(2,3,4,6‐tetra‐ ‐benzyl‐β‐
glucopyranosyl)‐7‐ ‐allylxanthone (23). To a solution of 19 glucopyranosyl)‐7‐
1053.4181.
1,3,6‐Tri‐ ‐benzyl‐2‐
‐(2,3,4,6‐tetra‐
O
C
O
D
‐
O
C
‐(2,3,4,6‐tetra‐
O‐benzyl‐β‐D‐
O
O
O‐acetyl‐β‐D‐
(166 mg, 0.143 mmol) in acetone (5 mL) was added K2CO3 (79 glucopyranosyl)xanthone (26). To a solution of accepter 24
mg, 0.572 mmol) and allyl bromide (20 µl, 0.224 mmol) at room (210 mg, 0.20 mmol), donor 25 (247 mg, 0.60 mmol) and TBAB
temperature. After being warmed to 60 °C and stirred for 2 h, (150 mg, 0.47 mmol) in CHCl3 (3 ml) was added 5% NaOH (aq,
the reaction mixture was cooled to rt and filtrated to remove 2ml). After being stirred for 5 h at 60 °C, the reaction mixture
the solid reagent. The combined filtrate was concentrated in was cooled to rt and then diluted with DCM (25 ml). The organic
vacuo to afford the crude intermediate 22. To a solution of the layers were washed with 1N HCl (aq) and brine, dried over
obtained compound 22 in MeOH (5 mL) was added Cs2CO3 (47 Na2SO4, concentrated, and purified by flash column
mg, 0.14 mmol) at room temperature. After being warmed to chromatography (PE‐EtOAc, 2:1 and DCM‐acetone, 20:1) to
75 °C and stirred overnight, the reaction mixture was cooled to afford 26 (196 mg, 71%) as a light yellow solid, with rotamers
rt and evaporated under reduced pressure. The residue was observed by 1H NMR and 13C NMR: [α]2D5 = ‐32.0 (c = 1.0, CHCl3);
dissolved in DCM and filtrated to remove the undissolved 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 0.7H), 8.00 (s, 0.3H), 7.63 –
substance, and the filtrate was concentrated and purified 7.00 (m, 33H), 6.97 – 6.77 (m, 3H), 6.67 (s, 0.3H), 6.62 (s, 0.7H),
directly by flash column chromatography (PE‐EtOAc, 3:1) to 5.43 – 4.67 (m, 14H), 4.64 – 4.07 (m, 8H), 4.02 – 3.21 (m, 6H),
afford 23 (162 mg, 95%) as a yellow solid, with rotamers 2.09 (s, 2H), 2.06 (s, 2H), 2.04 (s, 1H), 2.02 (s, 2H), 2.01 (s, 1H),
observed by 1H NMR and 13C NMR: [α]2D5 = +20.0 (c = 1.0, CHCl3); 1.93 (s, 1H), 1.82 (s, 2H), 1.80 (s, 1H) ppm; 13C NMR (100 MHz,
1H NMR (400 MHz, CDCl3) δ 7.81 – 6.74 (m, 37H), 6.58 (s, 1H), CDCl3)
6.22 – 5.92 (m, 1H), 5.55 – 4.14 (m, 20H), 3.85 – 3.29 (m, 5H) 169.3/169.3, 162.7/162.1, 160.8/159.5, 159.2, 154.6/154.5,
ppm; 13C NMR (100 MHz, CDCl3) δ 173.9/173.8, 162.5/161.8, 152.4/152.3,
144.3/144.2, 139.0/138.9, 138.8/138.6,
δ 173.7/173.5, 171.3/171.2, 170.3, 169.6/169.6,
160.7/159.5, 159.1/159.1, 154.2/154.1, 150.8/150.6, 146.1/ 138.4/138.3, 138.3/138.1, 137.6, 135.9/135.8, 135.7/135.6,
146.0, 141.1, 139.0/138.9, 138.8/138.6, 138.4/138.3, 128.8, 128.8, 128.6, 128.6, 128.5, 128.5, 128.4, 128.4, 128.3,
138.1/137.6, 136.0, 135.9/135.8, 132.9, 129.3, 129.0, 128.9, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.6,
128.7, 128.7, 128.5, 128.5, 128.4, 128.4, 128.4, 128.3, 128.2, 127.5, 127.4, 127.3, 127.1, 126.9, 119.0/118.1, 116.4/116.3,
128.0, 128.0, 127.9, 127.8, 127.7, 127.7, 127.5, 127.4, 127.3, 113.6, 111.2/110.4, 101.3/101.2, 100.3/100.1, 97.4/97.0,
127.2, 127.2, 127.1, 127.0, 126.9, 118.7/118.0, 117.9/117.9, 87.9/87.6, 80.7, 79.4/79.3, 78.5/ 78.3, 77.4/77.3, 75.5/75.2,
116.2/116.1, 111.1/110.3, 108.2/108.1, 101.1/101.0, 97.3/96.9, 75.1/75.0, 74.5/74.3, 73.9, 73.5/73.4, 73.0/72.8, 72.5/72.4,
87.9/87.6, 80.5/79.4, 78.5/78.4, 78.3/77.4, 75.4/75.1, 75.0/ 71.1/71.0, 70.5, 69.9/69.7, 69.2, 68.5, 62.2, 20.7, 20.7, 20.5,
74.9, 74.4/74.2, 74.0/73.4, 73.3/73.1, 71.1/70.9, 70.5/70.0,
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20.4 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for C82H79O20 [M + H]+
1383.5159, found 1383.5127.
5
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M. Richardson, Biochem. Sys. Ecol., 1984, 12, 1. (c) S. Cafferty,
J. Greenham and C. A. Williams, BiocheDmO.I:S1y0s.t1.0E3c9o/Cl.6, O19B90166,2224G
,
1,3,6‐Tri‐
O
‐acetyl‐2‐
C‐(2,3,4,6‐tetra‐
O
‐acetyl‐β‐
D‐
173. (d) A. J. Núñez Sellés and H. T. Vélez Castro, J. Agric. Food
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glucopyranosyl)‐7‐
O‐(2,3,4,6‐tetra‐
O‐acetyl‐β‐D‐
glucopyranosyl)xanthone (27). To a solution of 26 (50 mg,
0.036 mmol) in MeOH (2 mL) and EtOAc (2 mL) was added 10%
Pd(OH)2/C (20 mg). After being stirred under 1 atm of H2 for 2 d
at room temperature, the suspension was filtrated through
Celite to remove the solid catalyst. The filtrate was
concentrated in vacuo, and then dissolved in Pyridine (2 mL) at
room temperature. Anhydrous acetic anhydride (0.5 mL) was
added in, and the mixture was allowed to stir overnight before
being diluted with DCM. The organic layers were washed with
1N HCl (aq) and brine, concentrated, and purified by flash
column chromatography (PE‐ EtOAc, 1:1) to afford 27 (32 mg,
85%) as a light yellow solid, with rotamers observed by 1H NMR
and 13C NMR: [α]2D5 = +24.0 (c = 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 7.72 (s, 0.3H), 7.70 (s, 0.7H), 7.22 (s, 0.3H), 7.17 (s, 0.7H),
7.12 (s, 0.7H), 7.09 (s, 0.3H), 5.65 (t, J = 9.6 Hz, 0.7H), 5.57 (t, J =
9.6 Hz, 0.3H), 5.31 – 4.98 (m, 6H), 4.78 (t, J = 9.6 Hz, 1H), 4.44 –
4.28 (m, 1H), 4.24 – 4.09 (m, 2H), 4.05 – 3.96 (m, 1H), 3.92 (d, J
= 12.0 Hz, 1H), 3.75 (d, J = 7.6 Hz, 1H), 2.43 (s, 1H), 2.41 (s, 4H),
2.34 (s, 1H), 2.23 (s, 2H), 2.14 (s, 1H), 2.09 – 1.79 (m, 21H), 1.71
(s, 2H), 1.68 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ
173.6/173.3, 171.0/ 170.9, 170.6/170.5, 170.3, 170.0/169.9,
169.7, 169.6, 169.5/169.2, 168.4/168.2, 168.1, 167.7,
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157.4/157.1,
154.2/152.4,
151.3/150.9,
150.8/149.5,
146.1/146.0, 120.5/ 120.4, 118.2/117.9, 113.4/112.7,
112.8/112.1, 111.8/110.6, 110.4/110.0, 98.37, 76.9/76.6,
74.6/74.4, 72.8/72.5, 72.5/72.4, 70.5/70.3, 69.5/68.4,
68.2/68.0, 62.0/62.0, 21.4, 21.3, 20.8, 20.7, 20.7, 20.6, 20.6,
20.4, 20.4 ppm; HRMS (ESI‐FT‐ICR) m/z calcd for C47H50NaO27 [M
+ Na]+ 1069.2431, found 1069.2419.
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Acknowledgements
We are grateful for the financial support of the National Basic
Research Program of China (973 Program, Grant No.
2012CB822100), the National Key Technology R&D Program
“New Drug Innovation” of China (No. 2012ZX09502001‐001),
the National Natural Science Foundation of China (NSFC No.
21232002), the National Research Foundation for the Doctoral
Program of Higher Education of China (No.20130001110058),
and the Open Project Program of National Research Center for
Carbohydrate Synthesis, Jiangxi Normal University.
,
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