Total Synthesis of Myrmekioside A, a Mono-O-alkyl-diglycosylglycerol from Marine Sponge Myrmekioderma sp.

Article abstract of DOI:10.1002/ejoc.201500471

Myrmekioside A, which was isolated from the marine sponge Myrmekioderma sp. as a member of the family of natural mono-O-alkyl-diglycosylglycerols, and which has a strong reversion effect on the tumor cell morphology of ras-transformed cells at 5 μg/mL, wa

Full text of DOI:10.1002/ejoc.201500471

FULL PAPER
DOI: 10.1002/ejoc.201500471
Total Synthesis of Myrmekioside A, a Mono-O-alkyl-diglycosylglycerol from
Marine Sponge Myrmekioderma sp.
[a]
[a]
[a]
[a]
[a]
Jun Zhang, Chunxia Li,* Linlin Sun, Guangli Yu, and Huashi Guan
Keywords: Total synthesis / Natural products / Carbohydrates / Glycosides / Glycosylation / Glycolipids
Myrmekioside A, which was isolated from the marine sponge
Myrmekioderma sp. as a member of the family of natural
mono-O-alkyl-diglycosylglycerols, and which has a strong
reversion effect on the tumor cell morphology of ras-trans-
formed cells at 5 μg/mL, was synthesized for the first time in
bouring-group-participation approach using trichloroacet-
imidates and thioglycosides as glycosyl donors. The 2R abso-
lute configuration at C-2 of the glycerol backbone was de-
rived from (S)-1,2-isopropylideneglycerol (8). This synthetic
approach may be applicable to the preparation of other
myrmekioside analogues featuring different sugars and alkyl
chains for further structure–activity relationship studies.
1
7 steps and 14% overall yield. The β-glycosidic linkages in
myrmekioside A were successfully constructed by the neigh-
Introduction
A new family of glycolipids with a unique mono-O-alkyl-
diglycosylglycerol structure were isolated from the marine
sponges Myrmekioderma sp. and Trikentrion loeve, and
were reported to have potent antitumor activities.[ These
compounds all consisted of a glycerol backbone bearing an
alkyl chain and a xylose at the terminal hydroxyl positions,
and a mono- or diglucosyl unit or a monoglucosamine resi-
due attached to C-2 of the glycerol (Figure 1). Among these
compounds, myrmekiosides A–C, which all contain the
same sugar moieties but have different O-alkyl chains,
1]
showed antitumor effects against melanoma H-ras-trans-
formed NIH3T3 and THP1 cells.[
1b,2]
Myrmekioside E-2, a
peracetylated derivative of myrmekioside E, which contains
xylose and N-acetylglucosamine and a long alkyl chain with
a terminal alcohol group, was reported to inhibit the prolif-
eration of two human non-small-cell lung cancer cell lines
NSCLC-N6 and A549).[
3]
(
As a part of our continuing studies on the synthesis of
[
4]
therapeutically potent glycolipids from marine organisms,
we describe in this paper the first total synthesis of the
mono-O-alkyl-diglycosyl glycerol myrmekioside A, which
was isolated from the marine sponge Myrmekioderma sp.
Figure 1. Mono-O-alkyl-diglycosylglycerols from natural products.
Results and Discussion
[
a] Shandong Provincial Key Laboratory of Glycoscience and
The retrosynthetic analysis of myrmekioside A is shown
Ministry of Education, and School of Medicine and Pharmacy, in Scheme 1. After careful consideration of possible protect-
Glycoengineering, Key Laboratory of Marine Drugs of
Ocean University of China,
ing groups, we envisaged that myrmekioside A could be
5
Yushan Road, Qingdao 266003, Shandong Province, P. R.
China
synthesized by an etherification reaction between diglycos-
ylglycerol 2 and an alkyl unit 1 with an activating group.
Diglycosylglycerol 2 was disconnected into thioglycoside 4
and another diglycosylglycerol 3 at the β(1Ǟ2) linkage of
E-mail: lchunxia@ouc.edu.cn
http://web1.ouc.edu.cn/mp/4a/d0/c3932a19152/page.psp
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500471.
4246
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4246–4253

Total Synthesis of Myrmekioside A
Scheme 1. Retrosynthetic approach to myrmekioside A (P = protecting group; LG = leaving group).
the two glucose residues. To construct 3, we would require
imidate donor 6 with an acetyl protecting group at C-2 –
different from the protection of the other hydroxy groups –
which could be prepared from the peracetylated sugar via
the in situ generation of a glycosyl iodide.[ (S)-1,2-Iso-
propylideneglycerol 8 could be coupled to xylose unit 7 to
form chiral xylosylglycerol 5, consistent with natural abso-
lute 2R configuration at C-2 of the glycerol residue.
5]
Our initial efforts were aimed at the preparation of the
two glucose units 4 and 6 as shown in Scheme 2. Thio-
[
6]
glycoside donor 4 was synthesized from peracetylated
glucose 9 using thiocresol and BF ·OEt in dichlorometh-
3
2
[
7]
[5a]
ane. Imidate 6 was prepared in 70% overall yield, also
from starting material 9. Peracetylated glucose 9 was con-
verted into orthoester 11 via glycosyl iodide 10, which was
Scheme 2. Preparation of the building blocks 4 and 6. Reagents
and conditions: (a) p-thiocresol, BF ·OEt , CH Cl , 83%; (b) I
Et SiH, CH Cl ; (c) 2,6-lutidine, TBAI (tetrabutylammonium iod-
3
2
2
2
2
,
3
2
2
cyclized immediately in the presence of base and ethanol. ide), EtOH; (d) CH ONa, CH OH; (e) BnBr, NaH, DMF, 81%
3
3
2 3
The remaining three acetate groups of 11 were then re- over four steps; (f) pTsOH, dimethoxyethane/H O; (g) CNCCl ,
placed with benzyl groups to give orthoester 12[ in 88%
5b]
2 2
DBU, CH Cl , 87% over two steps.
yield. Acidic hydrolysis of 12 gave the corresponding hemi-
acetal, which was then treated with trichloroacetonitrile benzoylated xylose 13[12] in 88% yield by reaction with
(
CCl CN) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) thiocresol and BF ·OEt . With 7a in hand, we attempted its
3
3
2
[
8]
as a base to give glucosyl trichloroacetimidate 6 in 87% coupling with 8 under the conditions of N-iodosuccinimide
yield.
[
13]
(NIS) and trifluoromethanesulfonic acid (TfOH). Unfor-
To construct chiral xylosylglycerol 5a with a β-glycosidic tunately, the yield was rather disappointing because of the
linkage, perbenzoylated xylosyl donors 7a[ and 7b were low reactivity of the donor, and a glycoside with undesired
prepared to glycosylate with (S)-1,2-O-isopropylidene-sn- C-2 racemization of isopropylidene group was observed as
glycerol 8 using the neighbouring-group participation effect a by-product, even when excess DTBMP (2,6-di-tert-butyl-
9]
[10]
[
11]
(Scheme 3).
Thioglycoside 7a was synthesized from per- 4-methylpyridine) was added to prevent this racemiza-
Eur. J. Org. Chem. 2015, 4246–4253
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4247

J. Zhang, C. Li, L. Sun, G. Yu, H. Guan
FULL PAPER
tion.[14] Therefore, we turned our attention to the trichloro- with d-glucosyl donor 6 to deliver β-d-glucopyranoside 15a
acetimidate glycosylation methodology developed by in 93% yield. At this point, we encountered difficulties in
Schmidt, which would allow reaction with the chiral 1,2-O- selectively cleaving the C-2 acetyl group in the presence of
isopropylidene-sn-glycerol without racemization.[
15]
Re- the benzoyl groups under various hydrolysis conditions. Ini-
[
18]
moval of the p-toluenethio group using N-bromosuc- tial attempts with DBU/CH Cl2
or CSA (camphorsul-
2
[19]
cinimide (NBS) in acetone/water was followed by treatment fonic acid) in a CH OH/CH Cl (1:9) solvent mixture
3
2
2
[
10]
with CNCCl and DBU to give imidate donor 7b. Cou- were unsuccessful, and none of the product (i.e., 3a) was
3
pling of 7b with 8 using a catalytic amount of trimethylsilyl detected. This was probably due to steric hindrance around
trifluoromethanesulfonate (TMSOTf)[ in dichlorometh- the secondary 2-OH position as a result of the bulkiness of
ane gave the desired glycoside (i.e., 14a) as a single β isomer the anomeric substituent and the Bn group at C-3. Treat-
16]
[
20]
in 97% yield. Hydrolysis of 14a with pTsOH·H O in meth- ment of 15a with DBU in CH OH/CH Cl (1:1) or HCl/
2
3
2
2
[
21]
anol, and selective protection of the resulting xylosyl CH OH gave large amounts of undesired debenzoylated
3
glycerol with tert-butyldiphenylsilane (TBDPS)[
building block 5a in 74% yield over two steps.
17]
gave or desilylated (TBDPS) by-products, respectively, which
indicated that the TBDPS group was more stable to a basic
[
22]
With the building blocks in hand, we next attempted to environment than to acid-catalysed hydrolysis. Therefore,
prepare diglycosylglycerol 3a (Scheme 4). Under the we had to change the protecting groups on the xylose moi-
Schmidt glycosylation conditions of TMSOTf in dry ety to avoid the side-reactions during deacetylation of C-2
[
16]
CH Cl ,
xylosylglycerol derivative 5a was glycosylated of the glucose residue. We first attempted the direct glycos-
2
2
Scheme 3. Preparation of building block 5. Reagents and conditions: (a) p-thiocresol, BF
9:1); (c) DBU, CNCCl , CH Cl , 82% over two steps; (d) from 7a: NIS, TfOH, CH Cl
CH Cl , 97%; (e) pTsOH, CH OH; (f) TBDPSCl, DMAP [4-(dimethylamino)pyridine], pyridine, 74% over two steps.
3
·OEt
2 2 2
, CH Cl , 88%; (b) NBS, acetone/water
(
3
2
2
2
2
, 75% (isomeric mixture); from 7b: TMSOTf,
2
2
3
Scheme 4. Synthesis of diglycosylglycerol acceptor 3b.
248
4
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4246–4253

Total Synthesis of Myrmekioside A
[
23]
ylation of perbenzylated xylose imidate and 8, aiming to hydrolysed using CH ONa/CH OH
for at least 8 h to
3
3
prepare perbenzylated glycerol derivative 14b, but the prod- give product 3b with a free hydroxyl group at C-2 for the
uct proved to be an inseparable anomeric mixture (α/β = next glycosylation step.
1:1). Thus 14b was prepared from its benzoyl derivative 14a
With diglycosylglycerol acceptor 3b available, we carried
in 91% yield, and this was followed by a hydrolysis and out glycosylation with building block 4 using NIS/TfOH as
protection process to give xylosyl acceptor 5b in 86% yield. shown in Scheme 5 to obtain diglycosylglycerol 16. Re-
Glycosylation of 5b and 6 under Schmidt conditions pro- moval of the TBDPS protecting group of 16 by treatment
duced diglycosylglycerol 15b, which was quantitatively with tetrabutylammonium fluoride (TBAF) in THF yielded
Scheme 5. Synthesis of myrmekioside A.
Eur. J. Org. Chem. 2015, 4246–4253
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4249

J. Zhang, C. Li, L. Sun, G. Yu, H. Guan
a (98%). Generally, alkyl sulfonates or halides are used in peracetylated glucose 9 (5.0 g, 12.8 mmol). 1H NMR (600 MHz,
FULL PAPER
2
CDCl
H, ArH), 5.20 (t, J = 9.4 Hz, 1 H, 3-H), 5.02 (t, J = 9.8 Hz, 1 H,
-H), 4.92 (t, J = 9.8 Hz, 1 H, 4-H), 4.63 (d, J = 10.0 Hz, 1 H, 1-
H), 4.21 (dd, J = 12.2, 5.0 Hz, 1 H, 6-Ha), 4.16 (dd, J = 12.2,
3
): δ = 7.38 (d, J = 8.1 Hz, 2 H, ArH), 7.12 (d, J = 8.0 Hz, 2
etherification reactions with free hydroxyl groups under ba-
sic conditions. But under such conditions, acetyl groups
could potentially be hydrolysed, and indeed we observed
large amounts of hydrolysis by-products in the reaction of
hexadecyl methanesulfonate (1b) [1-hexadecanol (18;
2
2
2
.5 Hz, 1 H, 6-Hb), 3.69 (ddd, J = 10.1, 5.0, 2.5 Hz, 1 H, 5-H),
.35 (s, 3 H, PhCH ), 2.09, 2.08, 2.01, 1.98 (4 s, 12 H, 4 CH ) ppm.
3
3
1
(
.0 equiv.), MsCl (1.5 equiv.), Et N (0.8 equiv.), DMAP
+
3
MS (ESI): m/z = 477.1 [M + Na] .
0.1 equiv.), CH Cl , 95%] with compound 2a in the pres-
2 2
3
(
,4,6-Tri-O-benzyl-1,2-O-ethoxyethylidene-α-
D
-glucopyranose
12):[ Compound 12 (81% over four steps; exo/endo = 9:1) was
obtained from peracetylated glucose 9 (3.9 g, 10.0 mmol). R = 0.7
3
petroleum ether/EtOAc, 2:1, exo). H NMR (500 MHz, CDCl ,
ence of sodium hydride (NaH). In order to limit this deacet-
ylation, a coupling reaction between hexadecyl trichloro-
acetimidate (1a) [1-hexadecanol (18; 1.0 equiv.), CNCCl3
5b]
f
1
(
(
3.0 equiv.), DBU (0.6 equiv.), CH Cl , 81%] and 2a was
2 2
exo): δ = 7.35–7.17 (m, 15 H, ArH), 5.77 (d, J = 5.2 Hz, 1 H, 1-
H), 4.71 (d, J = 11.8 Hz, 1 H, PhCH), 4.61–4.57 (m, 3 H, 3 PhCH),
[24]
then attempted under acidic conditions (TfOH).
How-
ever, none of the desired product (i.e., 17) was detected.
4.50 (d, J = 12.1 Hz, 1 H, PhCH), 4.42 (dd, J = 5.2, 4.1 Hz, 1 H,
Thus, we had to convert 16 into its benzylated derivative 19 2-H), 4.39 (d, J = 11.5 Hz, 1 H, PhCH), 3.88 (t, J = 4.0 Hz, 1 H,
in 84% yield over two steps. Afterwards, the TBDPS group 3-H), 3.80–3.77 (m, 1 H, 5-H), 3.71 (dd, J = 9.5, 4.4 Hz, 1 H, 4-
was quantitatively removed to give 2b with a free hydroxyl H), 3.66–3.64 (m, 2 H, 2 6-H), 3.60–3.50 (m, 2 H, OCH
2
), 1.67 (s,
3
H, CH
3
), 1.20 (t, J = 7.0 Hz, 3 H, OCH CH ) ppm. MS (ESI):
2
3
group at the glycerol residue. Etherification of 2b with 1b
+
using NaH in dimethyl formamide (DMF)[ at 50 °C over-
25]
m/z = 515.2 [M – C H + Na] .
2 4
night successfully produced 20 in 70% yield. Final catalytic 3,4,6-Tri-O-benzyl-2-O-acetyl-α-
D
-glucopyranosyl Trichloroacetim-
hydrogenation using H /Pd(OH) generated the target com- idate (6):[ Compound 12 (0.52 g, 1.0 mmol) was dissolved in di-
5a]
2
2
pound myrmekioside A. The structure of the synthetic methoxyethane/H
compound was identified by H and C NMR spec-
2
O (10:1; 6.6 mL), and pTsOH (96 mg, 0.5 mmol)
was added at room temperature. After 2 h, the reaction mixture
was extracted with CH Cl (2ϫ 20 mL), and the organic phase was
washed with saturated NaHCO and brine, and dried (Na SO ),
and the solvents were evaporated in vacuo.
1
13
troscopy and HR-ESI-MS, all of which were consistent
2
2
with natural myrmekioside A.[2]
3
2
4
The residue was dissolved in CH Cl (10 mL), and the solution
2
2
Conclusions
3
was cooled to 0 °C. CCl CN (0.6 mL, 6.0 mmol) and DBU (44 μL,
0.3 mmol) were added. The mixture was stirred for 2 h, after which
The total synthesis of myrmekioside A, containing a chi-
ral glycerol backbone linked to xylose, a diglucose moiety,
time TLC indicated that the reaction was complete. The solution
was concentrated, and the residue was purified by column
and an long alkyl chain with a terminal alcohol group, was chromatography (petroleum ether/EtOAc, 6:1) to give 6 (0.55 g,
completed in 17 steps in 14% overall yield. To the best of 87% over two steps) as an oil. R = 0.7 (petroleum ether/EtOAc,
f
1
our knowledge, this is the first synthesis of this natural 3:1). H NMR (600 MHz, CDCl
3
): δ = 8.56 (s, 1 H, NH), 7.33–
7
.16 (m, 15 H, ArH), 6.52 (d, J = 3.5 Hz, 1 H, 1-H), 5.07 (dd, J =
0.0, 3.5 Hz, 1 H, 2-H), 4.85 (d, J = 11.5 Hz, 1 H, PhCH), 4.83 (d,
J = 10.6 Hz, 1 H, PhCH), 4.76 (d, J = 11.5 Hz, 1 H, PhCH), 4.63
d, J = 11.9 Hz, 1 H, PhCH), 4.77 (d, J = 10.6 Hz, 1 H, PhCH),
.50 (d, J = 11.9 Hz, 1 H, PhCH), 4.09 (t, J = 9.5 Hz, 1 H, 3-H),
.02–3.98 (m, 1 H, 5-H), 3.88 (d, J = 9.6 Hz, 1 H, 4-H), 3.81 (dd,
J = 11.1, 3.3 Hz, 1 H, 6-Ha), 3.69 (dd, J = 11.1, 1.6 Hz, 1 H, 6-
mono-O-alkyl-diglycosylglycerol. Strategies for protecting
groups and glycosylation conditions were studied and opti-
mized to ensure high stereo- and regioselectivity. The abso-
lute 2R configuration at C-2 of the glycerol residue in myr-
mekioside A was achieved by using commercially available
1
(
4
4
(S)-1,2-isopropylideneglycerol 8. The synthetic approach
presented here is of a modular character, and should thus
be applicable to other natural mono-O-alkyl-diglycosyl-
glycerols and structural variants.
+
Hb), 1.92 (s, 3 H, CH
3
) ppm. MS (ESI): m/z = 658.2 [M + Na] .
p-Methylphenyl 2,3,4-Tri-O-benzoyl-1-thio-β-
D
-xylopyranoside
9]
(
7a):[ Compound 7a (3.1 g, 88%) was obtained from perbenzoyl-
ated xylose 13 (3.5 g, 6.2 mmol). R
f
= 0.8 (petroleum ether/EtOAc,
1
2:1). H NMR (500 MHz, CDCl
3
): δ = 8.04–7.98 (m, 6 H, ArH),
Experimental Section
7.55–7.33 (m, 11 H, ArH), 7.14 (d, J = 8.3 Hz, 2 H, ArH), 5.76 (t,
J = 6.8 Hz, 1 H, 3-H), 5.43 (t, J = 6.6 Hz, 1 H, 2-H), 5.30–5.26
m, 1 H, 4-H), 5.19 (d, J = 6.6 Hz, 1 H, 1-H), 4.68 (dd, J = 12.2,
General Remarks: Solvents were purified in a conventional manner.
Thin-layer chromatography (TLC) was carried out on pre-coated
HSGF254 plates (Yantai, China). Flash column chromatography
was carried out on silica gel (200–300 mesh, Qingdao, China). Op-
tical rotations were determined with a Perkin–Elmer Model 241
MC polarimeter. 1H and C NMR spectra were recorded with
JEOL JNM-ECP 600 MHz and Agilent 500 MHz DD2 spectrome-
(
4
3
.2 Hz, 1 H, 5-Ha), 3.79 (dd, J = 12.2, 6.7 Hz, 1 H, 5-Hb), 2.35 (s,
H, CH
3
) ppm. MS (ESI): m/z = 591.3 [M + Na]+ 591.1.
2
,3,4-Tri-O-benzoyl-α- -xylopyranosyl Trichloroacetimidate
D
13
[10b]
(
7b):
colourless oil from 7a. R
NMR (500 MHz, CDCl ): δ = 8.04–7.98 (m, 4 H, ArH, NH), 7.58–
.30 (m, 12 H, ArH), 6.36 (d, J = 4.7 Hz, 1 H, 1-H), 5.82 (t, J =
.8 Hz, 1 H, 3-H), 5.62 (dd, J = 5.5, 4.8 Hz, 1 H, 2-H), 5.41–5.37
Compound 7b (82% over two steps) was obtained as a
1
f
= 0.7 (petroleum ether/EtOAc, 3:1). H
4
ters, using tetramethylsilane (Me Si) as an internal standard, and
3
chemical shifts are reported as δ values. Mass spectra were recorded
with Global Q-TOF and IonSpec 4.7 Tesla FTMS (MALDI/DHB)
mass spectrometers.
7
5
(
m, 1 H, 4-H), 4.57 (dd, J = 12.6, 3.5 Hz, 1 H, 5-Ha), 4.01 (dd, J
p-Methylphenyl 2,3,4,6-Tetra-O-acetyl-1-thio-β-
D
-glucopyranoside
= 12.6, 5.5 Hz, 1 H, 5-Hb) ppm. MS (ESI): m/z = 628.1 [M +
Na] .
[
6]
+
(4): Compound 4 (4.8 g, 83%) was obtained as a white solid from
4250
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4246–4253

Total Synthesis of Myrmekioside A
3
-O-(2Ј,3Ј,4Ј-Tri-O-benzoyl-β-
sn-glycerol (14a): (S)-1,2-Isopropylideneglycerol 8 (38 μL,
.31 mmol) and imidate 7b (0.16 g, 0.26 mmol) were dissolved in
dry CH Cl (15 mL). Molecular sieves (4 Å; 0.50 g) were added,
and the mixture was cooled to –15 °C under nitrogen. A solution
of TMSOTf (5 μL, 0.03 mmol) in CH Cl (1.0 mL) was added 165.44, 165.02, 138.17, 138.04, 137.88, 135.44, 135.42, 133.29–
dropwise over a period of 30 min. The mixture was stirred for
0 min at –15 °C, and then it was neutralized with Et N, and fil-
D
-xylopyranosyl)-1,2-isopropylidene- 3.89 (m, 2 H, 3sn-Ha, 2sn-H), 3.84 (dd, J = 10.5, 5.1 Hz, 1 H, 3sn
Hb), 3.74 (dd, J = 10.9, 4.0 Hz, 1 H, 1sn-Ha), 3.71–3.66 (m, 3 H,
4Ј-H, 2 6Ј-H), 3.62–3.54 (m, 3 H, 3Ј-H, 5ЈЈ-Hb, 1sn-Hb), 3.39 (dt,
J = 9.7, 3.0 Hz, 1 H, 5Ј-H), 1.82 (s, 3 H, CH ), 1.57 (s), 0.97 (s, 9
): δ = 169.50, 165.54,
-
0
2
2
3
1
3
3 3
H, 3 CH ) ppm. C NMR (126 MHz, CDCl
2
2
133.03, 129.87–127.67, 100.39, 100.26, 82.87, 78.31, 77.93, 74.99,
74.97, 74.94, 73.47, 73.23, 70.91, 70.79, 69.56, 68.63, 68.08, 63.28,
61.48, 26.78, 20.89, 19.16 ppm. MS (ESI): m/z = 1271.6 [M +
3
3
tered. The filtrate was concentrated. The residue was purified by
column chromatography (petroleum ether/EtOAc, 6:1) to give com-
+
Na] .
pound 14a (0.15 g, 97%) as a colourless solid. R
f
= 0.5 (petroleum
): δ = 8.01–7.96 (m,
H, ArH), 7.56–7.32 (m, 9 H, ArH), 5.75 (t, J = 7.0 Hz, 1 H, 3-
H), 5.37 (dd, J = 7.0, 5.3 Hz, 1 H, 2-H), 5.29 (td, J = 6.7, 4.2 Hz,
1
3-O-(2Ј,3Ј,4Ј-Tri-O-benzyl-β-
sn-glycerol (14b): Compound 14a (0.40 g, 0.69 mmol) was dissolved
in CH OH (8 mL), and a catalytic amount of NaOMe was added
D-xylopyranosyl)-1,2-isopropylidene-
ether/EtOAc, 3:1). H NMR (500 MHz, CDCl
3
6
3
until pH 9.0. The reaction mixture was stirred for 30 min, after
1
1
H, 4-H), 4.88 (d, J = 5.4 Hz, 1 H, 1-H), 4.46 (dd, J = 12.2, 4.2 Hz,
H, 5-Ha), 4.31–4.26 (m, 1 H, 2sn-H), 3.97 (dd, J = 8.6, 6.5 Hz, 1
+
which time it was neutralized with Amberlite IR120 resin (H ).
The mixture was then filtered, and the filtrate was concentrated in
vacuo.
H, 1sn-Ha), 3.94 (dd, J = 10.1, 5.1 Hz, 1 H, 3sn-Ha), 3.75–3.70 (m,
H, 5-Hb, 1sn-Hb), 3.58 (dd, J = 10.0, 5.9 Hz, 1 H, 3sn-Hb), 1.34
s, 3 H, CH ), 1.32 (s, 3 H, CH ) ppm. MS (ESI): m/z = 599.3 [M
2
(
+
3
3
The residue was dissolved in DMF (10 mL), and then NaH (0.11 g,
+
Na] .
2.65 mmol) and BnBr (0.32 mL, 2.65 mmol) were added at 0 °C.
The mixture was stirred for 1.5 h, then it was quenched with
1
-O-tert-Butyldiphenylsilyl-3-O-(2Ј,3Ј,4Ј-tri-O-benzoyl-β-
anosyl)-sn-glycerol (5a): pTsOH (0.13 g, 0.69 mmol) was added to
a solution of 14a (0.80 g, 1.39 mmol) in CH OH (16 mL) at room
D-xylopyr-
CH
3
OH (5 mL) and concentrated. The residue was dissolved in
Cl (30 mL), and the solution was washed with brine, dried
SO , and concentrated. The residue was purified by col-
umn chromatography (petroleum ether/EtOAc, 8:1) to give 14b
CH
2
2
3
with Na
2
4
temperature. The mixture was stirred for 2 h, then it was concen-
trated, and the residue was purified by column chromatography
(
0.34 g, 91% over two steps) as a syrup. R
f
= 0.8 (petroleum ether/
): δ = 7.36–7.27 (m, 15
(petroleum ether/EtOAc, 1:1).
1
EtOAc, 3:1). H NMR (500 MHz, CDCl
3
The product was dissolved in dry pyridine (15 mL) at room tempar-
ature, and DMAP (32 mg, 0.26 mmol) and TBDPSCl (0.37 mL,
1
night. After this time, TLC analysis showed complete consumption
of the starting material, and the mixture was evaporated in vacuo.
H, ArH), 4.88 (d, J = 11.0 Hz, 1 H, PhCH), 4.85 (d, J = 2.2 Hz, 2
H, 2 PhCH), 4.72 (d, J = 11.6 Hz, 1 H, PhCH), 4.70 (d, J =
.40 mmol) were added. The reaction mixture was stirred over-
1
1.0 Hz, 1 H, PhCH), 4.62 (d, J = 11.6 Hz, 1 H, PhCH), 4.36 (d,
J = 7.6 Hz, 1 H, 1-H), 4.32–4.27 (m, 1 H, 2sn-H), 4.05 (dd, J = 8.1,
.4 Hz, 1 H, 1sn-Ha), 3.94 (dd, J = 11.8, 5.1 Hz, 1 H, 5-Ha), 3.91
dd, J = 10.3, 5.1 Hz, 1 H, 3sn-Ha), 3.80 (dd, J = 8.3, 6.1 Hz, 1 H,
6
The residue was dissolved in CH
was washed with aq. HCl (1 m) and brine, dried with Na
concentrated. The residue was purified by column chromatography
petroleum ether/EtOAc, 4:1) to give compound 5a (1.28 g, 74%
over two steps) as an oil. R = 0.5 (petroleum ether/EtOAc, 3:1);
): δ = 8.00–7.93 (m, 6 H, ArH), 7.61–
.25 (m, 19 H, ArH), 5.75 (t, J = 7.2 Hz, 1 H, 3-H), 5.35 (dd, J = 1-O-tert-Butyldiphenylsilyl-3-O-(2Ј,3Ј,4Ј-tri-O-benzyl-β-
.3, 5.4 Hz, 1 H, 2-H), 5.29 (td, J = 6.9, 4.4 Hz, 1 H, 4-H), 4.83
anosyl)-sn-glycerol (5b): pTsOH (80 mg, 0.42 mmol) was added to
a solution of 14b (0.45 g, 0.85 mmol) in CH OH (10 mL) at room
.89–3.85 (m, 2 H, 2 3sn-H), 3.77–3.72 (m, 1 H, 2sn-H), 3.68 (dd, J temperature. The mixture was stirred for 3 h, then it was concen-
2
Cl
2
(30 mL), and the solution
(
2
SO , and
4
1
7
3
sn-Hb), 3.63–3.54 (m, 3 H, 3-H, 4-H, 3sn-Hb), 3.38 (dd, J = 8.8,
.6 Hz, 1 H, 2-H), 3.20 (dd, J = 11.5, 9.8 Hz, 1 H, 5-Hb), 1.41 (s,
(
3 3
H, CH ), 1.36 (s, 3 H, CH ) ppm. MS (ESI): m/z = 557.3 [M +
+
f
Na] .
1
H NMR (500 MHz, CDCl
3
7
7
D-xylopyr-
(d, J = 5.4 Hz, 1 H, 1-H), 4.41 (dd, J = 12.2, 4.4 Hz, 1 H, 5-Ha),
3
3
=
12.2, 7.1 Hz, 1 H, 5-Hb), 3.66 (d, J = 4.9 Hz, 2 H, 2 1sn-H), 2.57 trated, and the residue was purified by column chromatography
(
=
d, J = 4.9 Hz, 1 H, OH), 1.03 (s, 9 H, 3 CH
797.3 [M + Na] .
3
) ppm. MS (ESI): m/z
(petroleum ether/EtOAc, 1:1).
+
The product was dissolved in dry pyridine (12 mL), and DMAP
1-O-tert-Butyldiphenylsilyl-2-O-(2Ј-O-acetyl-3Ј,4Ј,6Ј-tri-O-benzoyl- (20 mg, 0.17 mmol) and TBDPSCl (0.34 mL, 1.26 mmol) were
β-
yl)-sn-glycerol (15a): Compound 5a (0.21 g, 0.27 mmol) and com-
pound 6 (0.20 g, 0.31 mmol) were dissolved in dry CH Cl
and molecular sieves (4 Å; 0.30 g) were added. The mixture was centrated in vacuo. The residue was dissolved in CH
D
-glucopyranosyl)-3-O-(2ЈЈ,3ЈЈ,4ЈЈ-tri-O-benzyl-β-
D
-xylopyranos-
added at room temparature. The reaction mixture was stirred over-
night, after which time TLC analysis revealed that the starting ma-
2
2
(8 mL), terial had been completely consumed. The mixture was then con-
Cl (30 mL),
and the solution was washed with aq. HCl (1 m) and brine, dried
with Na SO , and concentrated. The residue was purified by
2
2
cooled to 0 °C under nitrogen, and TMSOTf (7 μL, 0.03 mmol)
was added. The mixture was stirred for 30 min at 0 °C, and then it
2
4
3
was neutralized with Et N, and filtered. The filtrate was concen- chromatography (petroleum ether/EtOAc, 6:1) to give compound
trated. The residue was purified by column chromatography (petro-
5b (0.55 g, 90% over two steps) as an oil. R
EtOAc, 4:1). H NMR (500 MHz, CDCl
3
f
= 0.7 (petroleum ether/
): δ = 7.65–7.29 (m, 25
H, ArH), 4.85 (s, 2 H, 2 PhCH), 4.78 (d, J = 11.0 Hz, 1 H, PhCH),
): δ = 7.98–7.86 (m, 6 H, ArH), 7.54–7.17 (m, 34 4.72 (d, J = 11.6 Hz, 1 H, PhCH), 4.68 (d, J = 11.0 Hz, 1 H,
H, ArH), 5.75 (t, J = 7.8 Hz, 1 H, 3ЈЈ-H), 5.30 (dd, J = 8.0, 6.2 Hz, PhCH), 4.62 (d, J = 11.6 Hz, 1 H, PhCH), 4.33 (d, J = 7.6 Hz, 1
1
leum ether/EtOAc, 6:1) to give compound 15a (0.32 g, 93%) as
a white solid. R
500 MHz, CDCl
= 0.5 (petroleum ether/EtOAc, 3:1). 1H NMR
f
(
3
1
9
H, 2ЈЈ-H), 5.24 (td, J = 7.6, 4.6 Hz, 1 H, 4ЈЈ-H), 4.97 (dd, J =
.4, 8.2 Hz, 1 H, 2Ј-H), 4.92 (d, J = 6.1 Hz, 1 H, 1ЈЈ-H), 4.79–4.76 H, 2sn-H), 3.85–3.78 (m, 2 H, 2 3sn-H), 3.69 (dd, J = 10.3, 5.4 Hz,
H, 1-H), 3.91 (dd, J = 11.7, 4.8 Hz, 1 H, 5-Ha), 3.92–3.87 (m, 1
(
1
m, 2 H, 2 PhCH), 4.66 (d, J = 11.5 Hz, 1 H, PhCH), 4.61 (d, J =
2.2 Hz, 1 H, PhCH), 4.58 (d, J = 8.1 Hz, 1 H, 1Ј-H), 4.56–4.53
1 H, 1sn-Ha), 3.65 (dd, J = 10.3, 5.6 Hz, 1 H, 1sn-Hb), 3.61 (td, J
= 9.2, 4.9 Hz, 1 H, 4-H), 3.56 (t, J = 8.7 Hz, 1 H, 3-H), 3.56 (t, J
(m, 2 H, 2 PhCH), 4.28 (dd, J = 11.9, 4.5 Hz, 1 H, 5ЈЈ-Ha), 3.96– = 8.7 Hz, 1 H, 3-H), 3.35 (t, J = 8.2 Hz, 1 H, 2-H), 3.20 (dd, J =
Eur. J. Org. Chem. 2015, 4246–4253
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4251

J. Zhang, C. Li, L. Sun, G. Yu, H. Guan
FULL PAPER
1
=
1.6, 9.8 Hz, 1 H, 5-Hb), 1.05 (s, 9 H, 3 CH
755.5 [M + Na] .
3
) ppm. MS (ESI): m/z
1-O-tert-Butyldiphenylsilyl-2-O-[2Ј,3Ј,4Ј,6Ј-tetra-O-benzyl-β-
glucopyranosyl-(1ЈǞ2ЈЈ)-3ЈЈ,4ЈЈ,6ЈЈ-tri-O-benzyl-β- -glucopyranos-
yl]-3-O-(2ЈЈЈ,3ЈЈЈ,4ЈЈЈ-tri-O-benzyl-β- -xylopyranosyl)-sn-glycerol
(19): Compound 16 (0.20 g, 0.13 mmol) was dissolved in CH OH
D-
+
D
D
1
-O-tert-Butyldiphenylsilyl-2-O-(2Ј-O-acetyl-3Ј,4Ј,6Ј-tri-O-benzyl-β-
-glucopyranosyl)-3-O-(2ЈЈ,3ЈЈ,4ЈЈ-tri-O-benzyl-β- -xylopyranosyl)- (5 mL), and a catalytic amount of NaOMe was added until pH 9.0.
sn-glycerol (15b): Compound 5b (0.51 g, 0.70 mmol) and com-
The reaction mixture was stirred for 1 h, and then it was neutral-
pound 6 (0.48 g, 0.77 mmol) were dissolved in dry CH Cl (20 mL). ized with Amberlite IR120 resin (H ). The mixture was filtered,
3
D
D
+
2
2
Molecular sieves (4 Å; 0.50 g) were added, and the mixture was
cooled to 0 °C under nitrogen. TMSOTf (19 μL, 0.11 mmol) was
added. The mixture was stirred for 30 min at 0 °C, and then it was
neutralized with Et N, and filtered. The filtrate was concentrated.
3
The residue was purified by column chromatography (petroleum
and the filtrate was concentrated in vacuo.
The residue was dissolved in DMF (5 mL), and then NaH (32 mg,
0
.80 mmol) and BnBr (96 μL, 0.80 mmol) were added at 0 °C. The
mixture was stirred for 2 h at room temperature, then it was
quenched with CH OH (5 mL), and concentrated. The residue was
dissolved in CH Cl (20 mL), and the solution was washed with
brine (2ϫ 20mL), dried with Na SO , and concentrated. The resi-
due was purified by chromatography (petroleum ether/EtOAc, 8:1)
to give 19 (0.19 g, 84% over two steps) as a syrup. R = 0.7 (petro-
): δ = 7.69–
.64 (m, 4 H, ArH), 7.35–7.12 (m, 56 H, ArH), 4.84–4.72 (m, 9 H,
PhCH), 4.81 (d, J = 7.6 Hz, 1 H, 1Ј-H), 4.68–4.65 (m, 2 H, 2
3
ether/EtOAc, 6:1) to give compound 15b as a colourless oil (0.78 g,
= 0.75 (petroleum ether/EtOAc, 3:1). 1H NMR
2
2
9
3 %). R
f
2
4
(
500 MHz, CDCl
3
): δ = 7.62–7.18 (m, 40 H, ArH), 4.98 (dd, J =
.3, 8.1 Hz, 1 H, 2Ј-H), 4.83–4.76 (m, 4 H, 4 PhCH), 4.69–4.63 (m,
9
4
7
f
H, 3 PhCH, 1Ј-H), 4.59–4.48 (m, 5 H, 5 PhCH), 4.34 (d, J =
.6 Hz, 1 H, 1ЈЈ-H), 4.01–3.98 (m, 2 H, 2sn-H, 3sn-Ha), 3.87 (dd, J
1
leum ether/EtOAc, 3:1). H NMR (500 MHz, CDCl
3
7
9
=
10.7, 3.5 Hz, 1 H, 1sn-Ha), 3.81 (dd, J = 11.4, 4.6 Hz, 1 H, 5ЈЈ-
Ha), 3.75–3.64 (m, 5 H, 4Ј-H, 2 6Ј-H, 1sn-Hb, 3sn-Hb), 3.61 (t, J =
PhCH), 4.58 (d, J = 7.4 Hz, 1 H, 1ЈЈ-H), 4.56 (d, J = 11.7 Hz, 1
H, PhCH), 4.56–4.46 (m, 7 H, PhCH), 4.42 (d, J = 12.0 Hz, 1 H,
9
6
.2 Hz, 1 H, 3Ј-H), 3.53–3.48 (m, 2 H, 3ЈЈ-H, 4ЈЈ-H), 3.40 (dt, J =
.2, 2.7 Hz, 1 H, 5Ј-H), 3.24 (t, J = 8.1 Hz, 1 H, 2ЈЈ-H), 3.20 (dd,
PhCH), 4.29 (d, J = 7.6 Hz, 1 H, 1ЈЈЈ-H), 4.08–4.03 (m, 1 H, 2sn
H), 4.01 (dd, J = 10.2, 5.2 Hz, 1 H, 3sn-Ha), 3.86 (dd, J = 10.5,
.3 Hz, 1 H, 1sn-Ha), 3.85–3.80 (m, 2 H, 2ЈЈ-H, 1sn-Hb), 3.80 (dd,
J = 11.5, 4.9 Hz, 1 H, 5ЈЈЈ-Ha), 3.68 (dd, J = 10.2, 5.2 Hz, 1 H,
sn-Hb), 3.67–3.63 (m, 2 H, 2 6Ј-H), 3.61–3.56 (m, 4 H, 3Ј-H, 4Ј-
-
J = 11.3, 9.5 Hz, 1 H, 5ЈЈ-Hb), 1.77 (s, 3 H, CH
3
), 1.03 (s, 9 H, 3
) ppm. 1 C NMR (126 MHz, CDCl
3 3
CH ): δ = 169.49, 138.72,
3
5
1
1
7
6
1
38.53, 138.23, 138.18, 137.91, 135.54, 135.49, 133.33, 133.13,
29.71, 129.69, 128.42–127.35, 104.17, 100.76, 83.60, 82.98, 81.68,
8.38, 77.96, 77.87, 75.55, 75.08–74.51, 73.51, 73.22, 73.14, 68.76,
8.70, 64.06, 63.71, 26.80, 20.85, 19.18 ppm. MS (ESI): m/z =
3
H, 2 6ЈЈ-H), 3.54–3.45 (m, 4 H, 3ЈЈ-H, 4ЈЈ-H, 3ЈЈЈ-H, 4ЈЈЈ-H), 3.38
(ddd, J = 9.0, 5.3, 3.0 Hz, 1 H, 5Ј-H), 3.29–3.26 (m, 2 H, 2Ј-H,
+
229.7 [M + Na] .
2
9
ЈЈЈ-H), 3.23 (dt, J = 9.5, 2.6 Hz, 1 H, 5ЈЈ-H), 3.08 (dd, J = 11.6,
.7 Hz, 1 H, 5ЈЈЈ-Hb), 1.04 (s, 9 H, 3 CH ) ppm. MS (MALDI):
1
-O-tert-Butyldiphenylsilyl-2-O-[2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-β-D-
3
+
m/z = 1709.8 [M + Na] .
glucopyranosyl-(1ЈǞ2ЈЈ)-3ЈЈ,4ЈЈ,6ЈЈ-tri-O-benzyl-β-
yl]-3-O-(2ЈЈЈ,3ЈЈЈ,4ЈЈЈ-tri-O-acetyl-β- -xylopyranosyl)-sn-glycerol
16): NaOMe was added to a solution of 15b (0.50 g, 0.41 mmol)
in CH Cl /CH OH (1:5; 6 mL) until pH 9.0. The reaction mixture
D-glucopyranos-
D
1
-O-Hexadecyl-2-O-[2Ј,3Ј,4Ј,6Ј-tetra-O-benzyl-β-D-glucopyranosyl-
(
(
(
1ЈǞ2ЈЈ)-3ЈЈ,4ЈЈ,6ЈЈ-tri-O-benzyl-β- -glucopyranosyl]-3-O-
D
2
2
3
2ЈЈЈ,3ЈЈЈ,4ЈЈЈ-tri-O-benzyl-β- -xylopyranosyl)-sn-glycerol (20):
D
was stirred for 8 h, after which time it was neutralized with Am-
TBAF (1 m in THF; 120 μL, 0.12 mmol) was added to a solution
of 19 (0.14 g, 0.08 mmol) in THF (6 mL) at room temperature. The
mixture was stirred overnight, then it was concentrated. The resi-
due was purified by column chromatography (petroleum ether/
EtOAc, 4:1) to give compound 2b (0.12 g, 100%) as a syrup.
+
berlite IR120 resin (H ). The mixture was then filtered, and the
filtrate was concentrated in vacuo.
The residue (i.e., 3b) and compound 4 (0.27 g, 0.62 mmol) were
dissolved in dry CH
.30 g). The mixture was cooled to 0 °C under nitrogen, then NIS
0.14 g, 0.62 mmol) and TfOH (10 μL, 0.10 mmol) were added. The
mixture was stirred for 1 h, and then it was neutralized with Et N,
2 2
Cl (30 mL) with molecular sieves (4 Å;
0
(
The product (0.10 g, 0.07 mmol) was dissolved in dry DMF (3 mL),
and NaH (14 mg, 0.35 mmol) and 1b (112 mg, 0.35 mmol) were
added at at room temperature. The mixture was stirred at 40 °C
3
and filtered. The filtrate was concentrated. The residue was purified
by column chromatography (petroleum ether/EtOAc, 8:1) to give
overnight, then it was quenched with CH
The residue was purified by column chromatography (petroleum
f
ether/EtOAc, 10:1) to give 20 (80 mg, 70%) as a white solid. R =
3
OH, and concentrated.
compound 16 (0.56 g, 90% over two steps) as a white solid. R
f
=
1
1
0
.4 (petroleum ether/EtOAc, 3:1). H NMR (500 MHz, CDCl
7.69–7.66 (m, 4 H, ArH), 7.41–7.22 (m, 34 H, ArH), 7.10–7.08 = 7.35–7.14 (m, 50 H, ArH), 4.98 (d, J = 11.2 Hz, 1 H, PhCH),
m, 2 H, ArH), 5.02 (d, J = 9.7 Hz, 1 H, 3Ј-H), 4.97 (t, J = 9.7 Hz, 4.93 (d, J = 8.0 Hz, 1 H, 1Ј-H), 4.92 (d, J = 11.2 Hz, 1 H, PhCH),
3
): δ
3
0.8 (petroleum ether/EtOAc, 3:1). H NMR (500 MHz, CDCl ): δ
=
(
1
1
1
H, 4Ј-H), 4.92–4.85 (m, 2 H, 2Ј-H, PhCH), 4.84 (d, J = 11.0 Hz,
H, PhCH), 4.82 (d, J = 7.1 Hz, 1 H, 1Ј-H), 4.81 (d, J = 11.0 Hz, 4.69 (d, J = 7.5 Hz, 1 H, 1ЈЈ-H), 4.68–4.50 (m, 11 H, 11 PhCH),
H, PhCH), 4.76 (d, J = 11.2 Hz, 1 H, PhCH), 4.75–4.69 (m, 3
4.89 (d, J = 11.0 Hz, 1 H, PhCH), 4.86–4.71 (m, 6 H, 6 PhCH),
4.29 (d, J = 7.6 Hz, 1 H, 1ЈЈЈ-H), 4.08–4.03 (m, 1 H, 2sn-H), 4.00
(dd, J = 10.0, 4.6 Hz, 1 H, 3sn-Ha), 3.85 (dd, J = 8.5, 7.5 Hz, 1 H,
2ЈЈ-H), 3.82 (dd, J = 11.5, 4.9 Hz, 1 H, 5ЈЈЈ-Ha), 3.70–3.65 (m, 5
H, 3Ј-H, 3ЈЈ-H, 6ЈЈ-Ha, 1sn-Ha, 3sn-Hb), 3.65–3.58 (m, 4 H, 5Ј-H,
H, 3 PhCH), 4.62–4.59 (m, 2 H, 2 PhCH), 4.55 (d, J = 7.4 Hz, 1
H, 1ЈЈ-H), 4.53 (d, J = 12.4 Hz, 1 H, PhCH), 4.51 (d, J = 11.7 Hz,
1
1
H, PhCH), 4.47 (d, J = 12.3 Hz, 1 H, PhCH), 4.40 (d, J = 7.6 Hz,
H, 1ЈЈЈ-H), 4.09 (dd, J = 10.4, 4.7 Hz, 1 H, 3sn-Ha), 4.04–4.00 6Ј-Ha, 6ЈЈ-Hb, 1sn-Hb), 3.57–3.49 (m, 4 H, 4Ј-H, 4ЈЈ-H, 3ЈЈЈ-H, 4ЈЈЈ-
H), 3.46 (dt, J = 9.7, 3.2 Hz, 1 H, 5ЈЈ-H), 3.38 (dd, J = 8.8, 8.0 Hz,
1 H, 2Ј-H), 3.37–3.29 (m, 4 H, 6Ј-Hb, 2ЈЈЈ-H, OCH ), 3.10 (dd, J
ЈЈ-H, 4ЈЈ-H, 6ЈЈ-Ha, 4ЈЈЈ-H), 3.55–3.51 (m, 3 H, 3ЈЈ-H, 6ЈЈ-Hb, = 11.4, 9.7 Hz, 1 H, 5ЈЈЈ-Hb), 1.51–1.46 (m, 2 H, OCH CH ), 1.29–
ЈЈЈ-H), 3.38–3.34 (m, 1 H, 5Ј-H), 3.34 (t, J = 7.8 Hz, 1 H, 2ЈЈЈ-H), 1.22 [m, 26 H, (CH 13], 0.89 (t, J = 7.0 Hz, 3 H, CH
) ppm. 1
.31–3.29 (m, 1 H, 5ЈЈ-H), 3.15 (dd, J = 11.4, 9.8 Hz, 1 H, 5ЈЈЈ- NMR (126 MHz, CDCl ): δ = 138.89–138.19, 128.55–128.66,
(m, 2 H, 2sn-H, 6Ј-Ha), 3.90–3.78 (m, 4 H, 5ЈЈЈ-Ha, 2 1sn-H, 3sn
-
Hb), 3.76 (dd, J = 12.5, 1.8 Hz, 1 H, 6Ј-Hb), 3.62–3.56 (m, 4 H,
2
2
3
3
2
2
3
2
)
3
C
3
Hb), 1.98, 1.95, 1.88, 1.77 (4 s, 12 H, 4 CH
ppm. MS (ESI): m/z = 1517.6 [M + Na] .
3
), 1.05 (s, 9 H, 3 CH
3
)
104.48, 101.99, 101.52, 85.98, 84.97, 83.85, 83.26, 81.95, 78.33,
78.22, 78.06, 77.85, 75.77, 75.68, 75.35, 75.13, 75.04, 74.79, 73.81,
+
4252
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4246–4253

Total Synthesis of Myrmekioside A
7
3
3.59, 73.40, 71.95, 71.17, 69.54, 69.06, 68.93, 63.86, 32.08, 30.12,
J. Org. Chem. 2012, 49, 406–410; b) G. Dey, R. Bharti, R. Sen,
M. Mandal, Drug Discovery Today 2015, 20, 135–165.
[4] a) C. Li, Y. Sun, J. Zhang, Z. Zhao, G. Yu, H. Guan, Car-
bohydr. Res. 2013, 376, 15–23; b) Y. Sun, J. Zhang, C. Li, H.
Guan, G. Yu, Carbohydr. Res. 2012, 355, 6–12; c) J. Zhang, Y.
Sun, W. Wang, X. Zhang, C. Li, H. Guan, Carbohydr. Res.
2013, 381, 74–82.
0.12–29.82, 29.52, 26.42, 22.84, 14.28 ppm. HRMS (MALDI):
+
calcd. for C106
H
128
O
17Na 1695.9044 [M + Na] ; found 1695.8974.
1
-O-Hexadecyl-2-O-[β-
D
-glucopyranosyl-(1ЈǞ2ЈЈ)-β-
-xylopyranosyl-sn-glycerol (Myrmekioside A):[2]
OH (9:1; 3 mL) was
D-glucopyran-
osyl]-3-O-β-
solution of 20 (50 mg, 0.03 mmol) in THF/CH
treated with palladium hydroxide (10%; 50 mg), and the mixture
was stirred at room temperature under a hydrogen atmosphere for
D
A
3
[5] a) S. Loscher, R. Schobert, Chem. Eur. J. 2013, 19, 10619–
1
0624; b) M. Adinolfi, A. Iadonisi, A. Ravidà, M. Schiattar-
ella, Tetrahedron Lett. 2003, 44, 7863–7866.
1
h. The mixture was then filtered, and the solvent was evaporated
in vacuo to give myrmekioside A (22 mg, 96%) as a white solid. R
0.3 (CH Cl /CH N): δ =
OH, 5:1). 1H NMR (500 MHz, C
[
[
[
6] C. Denekamp, Y. Sandlers, J. Mass Spectrom. 2005, 40, 1055–
f
1063.
=
2
2
3
5 5
D
7] N. Khiar, M. Martin-Lomas, J. Org. Chem. 1995, 60, 7017–
021.
8] X. Liu, B. L. Stocker, P. H. Seeberger, J. Am. Chem. Soc. 2006,
28, 3638–3648.
5
4
6
.27 (d, J = 7.8 Hz, 1 H, 1Ј-H), 5.22 (d, J = 7.8 Hz, 1 H, 1ЈЈ-H),
.82 (d, J = 7.3 Hz, 1 H, 1ЈЈЈ-H), 4.57 (dd, J = 11.0, 2.5 Hz, 1 H,
7
Ј-Ha), 4.54–4.51 (m, 1 H, 2sn-H), 4.49–4.45 (m, 2 H, 6ЈЈ-Ha, 3sn
-
1
Ha), 4.38 (dd, J = 11.0, 5.2 Hz, 1 H, 6Ј-Hb), 4.33–4.28 (m, 3 H,
ЈЈЈ-Ha, 6ЈЈ-Hb, 3ЈЈ-H), 4.23–4.17 (m, 4 H, 3Ј-H, 4ЈЈ-H, 4ЈЈЈ-H, 3sn
Hb), 4.15–4.10 (m, 6 H, 4Ј-H, 2Ј-H, 2ЈЈ-H, 3ЈЈЈ-H, 2 1sn-H), 4.04–
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5
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.00 (m, 2 H, 2ЈЈЈ-H, 5Ј-H), 3.87 (ddd, J = 7.4, 4.7, 1.7 Hz, 1 H,
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H, OCH
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D N): δ = 106.47 (C-1Ј), 105.49 (C-1ЈЈЈ), 102.84 (C-1ЈЈ), 84.14
2
), 1.62–1.58 (m, 2 H, OCH
2 2
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[
[
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4
C
(C-2Ј), 79.17 (C-5ЈЈ), 78.74 (C-5Ј), 78.49 (C-3ЈЈ), 78.32 (C-3Ј, C-
1
3
7
3
3
2
ЈЈЈ), 78.11 (C-2sn), 76.79 (C-2ЈЈ), 75.16 (C-2ЈЈЈ), 72.21 (O-CH ),
2.17 (C-4ЈЈ), 71.64 (C-4Ј), 71.45 (C-4ЈЈЈ), 71.25 (C-1sn), 70.27 (C-
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HRMS (ESI): calcd. for C36
95.4355.
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[
Received: April 14, 2015
Published Online: May 28, 2015
Eur. J. Org. Chem. 2015, 4246–4253
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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