Synthesis of 1,3- and 2,3-diglycosylated indoles as potential trisaccharide mimetics

Article abstract of DOI:10.1055/s-0031-1290761

Diglycosylated heteroaromatics may serve as metabolically stable mimetics of trisaccharides. Herein, the preparation of several 1,3- and 2,3-diglycosylindoles by direct C-glycosylation of monoglycosylated precursors is described. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0031-1290761

PAPER
▌1385
paper
Synthesis of 1,3- and 2,3-Diglycosylated Indoles as Potential Trisaccharide
Mimetics
Diglycosylated Indoles
Christine Wiebe,a,b Silvia Fusté de la Sotilla,a Till Opatz*a
a
Institute for Organic Chemistry, University of Mainz, Duesbergweg 10–14, 55129 Mainz, Germany
b
Department of Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Fax +49(6131)3922338; E-Mail: opatz@uni-mainz.de
Received: 19.01.2012; Accepted after revision: 20.02.2012
Dedicated to Professor Hans Paulsen on the occasion of his 90th birthday
OAc
O
Abstract: Diglycosylated heteroaromatics may serve as metaboli-
BnO
cally stable mimetics of trisaccharides. Herein, the preparation of
several 1,3- and 2,3-diglycosylindoles by direct C-glycosylation of
monoglycosylated precursors is described.
O
HN
O
N
O
AcO
OAc
Key words: carbohydrates, indoles, glycosides, glycosylation,
electrophilic aromatic substitution
1,3-diglycosylindoles
2,3-diglycosylindoles
Figure 1 1,3- and 2,3-Diglycosylindoles
Structurally defined carbohydrates are known to play a vi-
tal role in many biological processes.1–4 As part of glyco-
proteins, glycolipids, and other conjugates, they are key
elements in a variety of processes such as signalling, cell–
cell communication, and molecular and cellular target-
ing.5,6 Their involvement in intercellular communication
has promoted considerable interest in the preparation of
carbohydrate mimetics as potential therapeutic agents.7 In
recent years, numerous efforts have been directed towards
the synthesis of C-glycosides in which a carbon atom re-
places the glycosidic oxygen.8–15 C-Glycosides attract at-
tention because they are stable towards chemical and
enzymatic hydrolysis whilst often retaining the capacity
to interact with the receptors for their natural counterparts.
C-Glycosides with an aromatic or heteroaromatic agly-
cone have been isolated from natural sources and some of
these compounds have been found to exhibit potent anti-
bacterial and antiproliferative activity.16
Synthesis of N-Glycosylindoles
N-Glycosylindoles 9–13 can be prepared according to
Melnik et al.22 by the indoline-indole method consisting in
the reaction of hexoses 1–4 with indoline followed by de-
hydrogenation with DDQ.23 Subsequent protection of the
hydroxy groups of the resulting N-glycosylindoles was
performed by peracetylation with acetic anhydride in pyr-
idine (method A, Scheme 1). Compounds 9–13 can also
be prepared by peracetylation of the glycosylindolines 7
and 8 followed by reaction with DDQ (method B).24
O
indoline, EtOH, 40 °C
O
HO
N
HO
OH
Among the various methods used for the construction of
C-glycosylated aromatics and heteroaromatics, the most
common approach is the reaction of an electron-rich nu-
cleophile with an electrophilic glycosyl donor.11 In this
context, electron-rich phenols,17–19 pyrroles,20 and
indoles21 represent effective C-nucleophiles, and are suit-
able templates for direct C-glycosylation. Herein, we re-
port on the reaction of O-glycosyl trichloroacetimidates
with 1- and 2-glycosylindoles in the presence of boron tri-
fluoride etherate to form, 1,3- and 2,3-diglycosylindoles,
respectively (Figure 1). These compounds may be viewed
as trisaccharide mimetics.
Gal 1, Fuc 2,
Glc 3, Man 4
Gal 5, Fuc 6,
Glc 7, Man 8
method A: a) DDQ, 1,4-dioxane, 25 °C
b) Ac2O, pyridine, 25 °C
O
method B: a) Ac2O, pyridine, 25 °C
b) DDQ, 1,4-dioxane, 25 °C
N
AcO
9–13
method A: Gal: 73% (β, 9), Fuc: 55% (β, 10)
method B: Glc: 89% (β, 11), Man: 20% (α, 12), 43% (β, 13)
Scheme 1 Preparation of N-glycosylindoles 9–13
The anomeric configuration of the galactosylindoline
could additionally be confirmed by X-ray crystallography
(Figure 2). A remarkable feature of this structure is the al-
most perfect antiperiplanar arrangement of the lone pair at
the pyramidal nitrogen atom of the indoline moiety and
the C1–O5 bond reflecting the n → σ* delocalisation, that
is, the exo-anomeric effect.
SYNTHESIS 2012, 44, 1385–1397
Advanced online publication: 10.04.2012
DOI: 10.1055/s-0031-1290761; Art ID: SS-2012-T0068-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1386
C. Wiebe et al.
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4 Å MS
BF3⋅OEt2
O
OAc
N
AcO
OAc
O
AcO
AcO
Gal 9, Fuc 10,
Glc 11, α-Man 12,
β-Man 13
AcO
14
Cl3C(HN)CO
AcO
OAc
O
O
N
OAc
OAc
Gal 16, Fuc 17,
Glc 18, α-Man 19,
β-Man 20a,b
Cl3C(HN)CO
O
OAc
OAc
AcO
Figure 2 Crystal structure of 1-(β-D-galactopyranosyl)indoline
5MeOH
OAc
OAc
15
O
O
4 Å MS
BF3⋅OEt2
N
AcO
AcO
1,3-Diglycosylindoles
Gal 21, Fuc 22,
Glc 23, Man 24
The trichloroacetimidates introduced by Schmidt25–27 ex-
hibit a favourable reactivity and permit C-glycosylations
under relatively mild conditions.17 Boron trifluoride–di-
ethyl etherate promoted the reaction of N-glycosylindoles
9–13 with mannose or fucose trichloroacetimidate donors
14/15 and furnished 1,3-diglycosylindoles in moderate
yield (Scheme 2, Table 1).
Scheme 2 C-Glycosylation of N-glycosylindoles 9–13 with manno-
syl and fucosyl trichloroacetimidates 14 and 15
Nu
Nu
OAc
O
O
O
AcO
AcO
O
O
O
OAc
OAc
In the case of mannose, a high α-selectivity was observed.
The preference for the formation of the α-anomer is con-
sistent with the literature and was observed with various
carbon nucleophiles, protecting groups, and solvents.13,28–30
The high selectivity is mainly due to neighbouring group
participation31,32 of the 2-O-acetyl group and the anomeric
effect (Figure 3).
Nu
Nu
mannose
fucose
Figure 3 Neighbouring group participation of the 2-O-acetyl group
as major side product. This is due to the attack of indole at
C-2 of the acyloxonium intermediate.
An exception seems to be compound 20, where a prefer-
ential formation of the β-mannoside was observed as
judged by NOESY data. Unfortunately, acetyl-protected
donors lead to extensive transfer of acetyl groups from O-
233 to the nucleophile34,35 to form the 3-acetylated indole
Remarkably, the reaction of N-glycosylindoles with the
analogous galactose or glucose trichloroacetimidate do-
nors under identical conditions did not yield the desired
diglycosylindoles (data not shown).
Table 1 Preparation of 1,3-Diglycosylindoles
Entry
Glycosylindole
Donor
Temp (°C)
Product
Configuration
Yield (%)
of the 3-residue
1
2
3
4
5
6
7
8
9
β-Gal (9)
α-Man (14)
α-Man (14)
α-Man (14)
α-Man (14)
α-Man (14)
α-Fuc (15)
α-Fuc (15)
α-Fuc (15)
α-Fuc (15)
–60 → 0
–15 → 3
–15 → 8
–15 → 7
–25 → 10
–60 → 0
–15 → 3
–15 → 8
–20 → 10
16
17
18
19
20
21
22
23
24
only α
55
β-Fuc (10)
β-Glc (11)
α-Man (12)
β-Man (13)
β-Gal (9)
only α
32
only α
48
only α
16
1:2.6 (α:β)
only β
25 (combined)
33
β-Fuc (10)
β-Glc (11)
α-Man (12)
1:2 (α:β)
1:2 (α:β)
only β
24 (combined)
45 (combined)
36
Synthesis 2012, 44, 1385–1397
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PAPER
Diglycosylated Indoles
1387
Synthesis of 2-Glycosylindoles
AcO
Cl3C(HN)CO
O
OAc
O
O
BnO
OAc
BnO
2-Glycosylindoles could be obtained by the method estab-
lished by Nishikawa et al.36,37 C-Glycosylation of glyco-
syl acetates 27–29 with tributyl[2-(trimethyl-
silyl)ethynyl]stannane in the presence of TMSOTf as pro-
moter gave exclusively the corresponding α-configured
TMS-glycosylacetylenes 30–32, which were desilylated
with TBAF. Sonogashira-coupling with N-tosyl-2-iodo-
aniline (33) followed by Cu(I)-catalysed cyclisation38
yielded N-tosylindoles 34–36, which were deprotected by
alkaline detosylation to give 2-glycosylindoles 37–39
(Scheme 3).
O
OAc
14
AcO
HN
OAc
HN
Gal 37,
Glc 39
4 Å MS
BF3⋅OEt2
Gal 41,
Glc 44
OAc
OAc
O
O
AcO
BnO
AcO
OAc
Cl3C(HN)CO
15
O
OAc
HN
4 Å MS
BF3⋅OEt2
Gal 40,
Glc 43
OAc
OAc
Cl3C(HN)CO
O
a)
Bu3Sn
TMSOTf, THF, 25 °C
TMS
OAc
OAc
O
OAc
b) TBAF, THF–H2O, 25 °C
I
O
BnO
Gal 30,
Fuc 31,
Glc 32
OAc
14
O
AcO
BnO
HN
HN
O
OAc
AcO
OBn
Gal 27, Fuc 28,
Glc 29
4 Å MS
BF3⋅OEt2
O
OBn
TsHN
OBn
O
OBn
BnO
BnO
BnO
38
33
Pd(OAc)2
CuI, Ph3P, Et3N, DMF, 60 °C
42
TsN
Scheme 4 Preparation of 2,3-diglycosylindoles
Gal 34,
Fuc 35,
Glc 36
O
BnO
was deduced from NOESY contacts between the three ax-
ial protons in positions H-1, H-3, and H-5. Again, acety-
lation of the 3-position of the indole is observed as a side
reaction.
HN
TBAF, 65 °C, 5 d
Gal 37,
Fuc 38,
Glc 39
In summary, C-glycosylation of various 1- and 2-glyco-
sylindoles with 2,3,4,6-tetra-O-acetyl-α-D-mannopyrano-
syl trichloroacetimidate 14 and 2,3,4-tri-O-acetyl-α-L-
fucopyranosyl trichloroacetimidate 15 using boron tri-
fluoride–diethyl etherate as promoter furnished various
diglycosylindoles. These compounds may serve as build-
ing blocks for the synthesis of functional glycomimetics
with improved metabolic stability.
Scheme 3 Preparation of 2-glycosylindoles
2,3-Diglycosylindoles
2,3-Diglycosylindoles can be readily prepared from 2-
glycosylindoles 37–39 by boron trifluoride–diethyl ether-
ate promoted reaction with mannose- or fucose-derived
trichloroacetimidate donors 14 and 15.39 This exclusively
leads to the β-C-glycosides, the stereochemistry of which
could be readily established by NMR spectroscopy
(Scheme 4, Table 2). This is presumably due to strong 1,3-
diaxial interactions in the thermodynamically unfavour-
able α-anomer.
1,3-Diglycosylindoles themselves may be viewed as mi-
metics of trisaccharides possessing a ‘linear’ shape
whereas the sterically more demanding 2,3-diglycosylin-
doles represent mimetics of carbohydrates with a vicinal
substitution pattern.
Moisture-sensitive reactions were carried out under argon atmo-
sphere in dried glassware sealed by rubber septa. Unless otherwise
specified, chemicals were obtained from commercial suppliers and
were used without further purification. CH2Cl2 was dried over CaH2
Since the determination of the configuration at the ano-
meric centre in C-mannosides cannot be based on the vic-
inal coupling constant of H-1, the relative configuration
Table 2 Preparation of 2,3-Diglycosylindoles
Entry
Glycosylindole
Donor
Temp
(°C)
Product
Configuration
of the 3-residue
Yield
(%)
1
2
3
4
5
α-Gal (37)
α-Gal (37)
α-Fuc (38)
α-Glc (39)
α-Glc (39)
α-Man (14)
α-Fuc (15)
α-Fuc (15)
α-Man (14)
α-Fuc (15)
–60 → 0
40
41
42
43
44
only β
only β
only β
only β
only β
23
46
50
34
54
–47 → –2
–20 → –2
–20 → –2
–20 → –2
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397

1388
C. Wiebe et al.
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and distilled under argon atmosphere prior to use. Molecular sieves
were activated by heating in vacuo. Flash chromatography was per-
formed on silica gel 60 (0.035–0.070 mm, Acros). Chromatography
solvents (cyclohexane, EtOAc) were distilled prior to use. For ana-
lytical TLC, Merck silica gel aluminum sheets (60 F254) were used.
Visualisation was accomplished by UV light (254 nm) and sugar
reagent40 (1 M ethanolic H2SO4–0.2% ethanolic 3-methoxyphenol
solution 1:1). Analytical HPLC was performed on a Knauer Nu-
cleosil 100-5 column (250 × 4.6 mm). Preparative HPLC was ac-
complished using a Knauer Nucleosil 100-10 column (250 × 40
mm) at a flow rate of 50 mL/min.
1H and 13C NMR spectra were recorded on a Bruker AC 300, AV
400 or DRX 500 in CDCl3 or CD3OD using the residual solvent
peak as internal reference (CDCl3, δH = 7.26, δC = 77.16, CD3OD,
δH = 3.31, δC = 49.0). Optical rotations were measured at r.t. on a
Krüss P8000 polarimeter at 589 nm or on a Perkin-Elmer 241 polar-
imeter at 546 and 578 nm. In the latter case, the optical rotation at
589 nm was extrapolated using the Drude equation. IR spectra were
recorded on a ThermoNicolet Avatar 370 FT-IR spectrometer or a
Bruker Tensor 27 FT-IR spectrometer using a diamond ATR unit.
FAB mass spectrometry was carried out on with a VG70S (Xe-FAB
ionisation) with m-nitrobenzyl alcohol as the matrix. For exact mass
determination (FAB-HRMS), PEG 300, or PEG 600 was used as in-
ternal standard. ESI mass spectrometry was carried out on an Agi-
lent 1200 LC/MSD Trap XCT. The samples were dissolved in
MeCN (c 0.1 g/L) and injected via an Agilent 1200 HPLC with an
Ascentis Express C8 (30 × 2 mm, 2.7 μm particle size) column
(MeCN–H2O, 80:20, flow rate: 0.5 mL/min). Exact mass determi-
nation (ESI-HRMS) was carried out on a Q-ToF-Ultima 3-Instru-
ment with a Lock Spray interface. NaI/CsI clusters were used as an
external reference.
0.08 × 0.36 × 0.6 mm3 colourless plate. T = –80 °C, D = 1.347
g·cm–3. Turbo-CAD4, Cu-Kα, 2° ≤ θ < 70°, 0 ≤ h ≤ 8, 0 ≤ k ≤ 10, 0
≤ l ≤ 33. Reflections collected: 3386, independent reflections, 2832
(Rint = 0.0511), R1 = 0.0485, wR2 = 0.1311.
1-(β-L-Fucopyranosyl)indoline (6)
The title compound was prepared according to the general proce-
dure from indoline (4.76 g, 42.5 mmol) and L-fucose (3.17 g, 19.3
mmol) in EtOH (300 mL) and H2O (7.2 mL). The reaction mixture
was heated to reflux for 20 h. The crude product was purified by
flash chromatography (eluent: EtOAc–EtOH, 30:1) to give 6 (5.14
g, quant.); beige solid; mp 66–67 °C; Rf = 0.52 (CHCl3–MeOH–
AcOH, 5:1:0.1); [α]D22 –10.7 (c = 1.00, MeOH).
IR (ATR): 3427, 2981, 2939, 2886, 1605, 1489, 1415, 1379, 1265,
1167, 1103, 1071, 1024, 997, 904, 859 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.06–7.10 (m, 2 H, H-4ind, H-6ind),
6.75 (t, 3J5,4/6 = 7.4 Hz, 1 H, H-5ind), 6.62 (d, 3J7,6 = 7.8 Hz, 1 H, H-
7ind), 4.64 (d, 3J1,2 = 9.0 Hz, 1 H, H-1fuc), 3.91 (t, 3J2,3/4 = 9.0 Hz, 1
H, H-2fuc), 3.55–3.73 (m, 5 H, H-3fuc, H-4fuc, H-5fuc, H2-2ind), 2.97–
3.02 (m, 2 H, H2-3ind), 2.65 (br s, 1 H, OH), 1.23 (d, 3J6,5 = 6.5 Hz,
3 H, H-6fuc).
MS (ESI): m/z (%) = 266.1 ([M + H]+, 100), 288.1 ([M + Na]+, 10).
ESI-HRMS: m/z calcd for [C14H19NO9 + H]+: 266.1392; found:
266.1390.
1-(β-D-Glucopyranosyl)indoline (7)
The title compound was prepared according to the general proce-
dure from indoline (5.32 mL, 47.4 mmol) and D-glucose (3.98 g,
22.1 mmol) in a mixture of EtOH (345 mL) and H2O (8.5 mL). The
reaction mixture was heated to reflux for 26 h. The crude product
was purified by flash chromatography (eluent: EtOAc–MeOH,
15:1) to give 7 (6.41 g, quant.); rose-coloured foam; Rf = 0.41
(CHCl3–MeOH–AcOH, 5:1:0.1); [α]D22 –11.8 (c = 1.00, MeOH).
N-Glycosylindolines; General Procedure
To a solution of indoline in a mixture of EtOH and H2O was added
the respective hexose. The reaction mixture was heated to reflux
overnight and concentrated under reduced pressure.
IR (ATR): 3391, 2931, 2907, 2882, 1605, 1491, 1464, 1417, 1372,
1333, 1265, 1082, 1021, 756 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 6.94–7.02 (m, 2 H, H-4ind, H-
6ind), 6.54–6.60 (m, 2 H, H-5ind, H-7ind), 5.02 (br s, 2 H, OH), 4.93
(br s, 2 H, OH), 4.64 (d, 3J1,2 = 8.4 Hz, 1 H, H-1glc), 3.07–3.67 (m,
8 H, H-2glc, H-3glc, H-4glc, H-5glc, H-6a,bglc, H2-2ind), 2.87–2.94 (m,
2 H, H2-3ind).
MS (ESI): m/z (%) = 282.2 ([M + H]+, 100), 304.2 ([M + Na]+, 20).
ESI-HRMS: m/z calcd for [C14H19NO5 + Na]+: 304.1161; found:
1-(β-D-Galactopyranosyl)indoline (5)
The title compound was prepared according to the general proce-
dure from indoline (2.00 g, 16.8 mmol) and D-galactose (1.41 g,
7.82 mmol) in EtOH (120 mL) and H2O (4 mL). The reaction mix-
ture was heated to reflux for 17.5 h. The crude product was purified
by flash chromatography (eluent EtOAc–MeOH, 40:1) to afford 5
(1.80 g, 82%); colourless solid; mp 137.4–137.7 °C; Rf = 0.30
(CHCl3–MeOH–AcOH, 5:1:0.1); [α]D22 +3.3 (c = 1.00, MeOH).
304.1158.
IR (ATR): 3425, 2910, 1608, 1486, 1409, 1257, 1080, 1034 cm–1.
1H NMR, COSY (500 MHz, CD3OD): δ = 7.00 (d, 3J3,4 = 7.2 Hz, 1
H, H-3ind), 6.95 (t, 3J6,5/7 = 7.6 Hz, 1 H, H-6ind), 6.54–6.58 (m, 2 H,
H-5ind, H-7ind), 4.86 (d, 3J = 5.1 Hz, 1 H, OH), 4.80 (d, 3J = 5.5 Hz,
1 H, OH), (d, 3J1,2 = 8.9 Hz, 1 H, H-1gal), 4.36 (d, 3J = 4.5 Hz, 1 H,
OH), 3.59–3.71 (m, 3 H, H-2gal, H-3gal, H-2ind), 3.33–3.51 (m, 5 H,
H-4gal, H-5gal, H-6a,bgal, H-2ind), 2.83–2.97 (m, 2 H, H2-3ind).
13C NMR, HSQC (101 MHz, DMSO-d6): δ = 150.7 (C-7aind), 129.6
(C-3aind), 126.9 (C-6ind), 124.3 (C-4ind), 117.5 (C-5ind), 107.5 (C-
7ind), 85.7 (C-1gal), 76.4, 74.4 (C-4gal, C-5gal), 68.4, 67.7 (C-2gal, C-
3gal), 60.4 (C-6gal), 45.4 (C-2ind), 27.6 (C-3ind).
1-(α/β-D-Mannopyranosyl)indoline (8)
The title compound was prepared according to the general proce-
dure from indoline (6.67 mL, 59.6 mmol) and D-glucose (5.00 g,
27.8 mmol) in a mixture of EtOH (355 mL) and H2O (14 mL). The
reaction mixture was heated to reflux for 26 h. The crude product
was purified by flash chromatography (eluent: EtOAc–MeOH,
15:1) to give product 8 (5.73 g, 69%) as a mixture of anomers
(α/β = 1:2.3, determined by NMR spectroscopy); yellow oil;
Rf = 0.37 (CHCl3–MeOH–AcOH, 5:1:0.1).
1H NMR (300 MHz, DMSO-d6): δ = 7.07 (d, 3J3,4 = 7.1 Hz, 1 H, H-
3ind), 7.69 (t, 3J6,5/7 = 7.7 Hz, 1 H, H-6ind), 6.57–6.63 (m, 2 H, H-5ind
,
MS (FAB): m/z (%) = 281.1 ([M]+, 100), 282.1 ([M + H]+, 90).
H-7ind), 4.78 (mc, 1 H), 4.73 (s, 1 H), 4.60 (d, J = 5.5 Hz, 0.4 H),
4.36 (t, J = 5.5 Hz, 0.4 H), 4.83 (mc, 1 H), 3.61–3.77 (m, 3 H),
3.34–3.45 (m, 5 H), 3.16–3.22 (m, 1H), 2.82–2.88 (m 2 H).
FAB-HRMS: m/z calcd for [C14H19NO5]+: 281.1263; found:
281.1259; m/z calcd for [C14H19NO5 + H]+: 282.1341; found:
282.1336.
13C NMR (101 MHz, DMSO-d6): δ = 151.4 (C-7aind), 129.2 (C-
3aind), 126.9 (C-6ind), 124.1 (C-4ind), 117.9 (C-5ind), 108.2 (C-7ind),
84.24, 84.21 (C-1manα/β), 79.2 (C-5manα/β), 74.54, 74.46 (C-3manα/β),
71.44, 71.34 (C-2manα/β), 67.12, 67.02 (C-4manα/β), 61.32, 61.21 (C-
6manα/β), 48.2 (C-2ind), 28.2 (C-3ind).
Anal. Calcd for C14H19NO5: C, 59.78; H, 6.81; N, 4.98. Found: C,
59.77; H, 6.88; N, 5.03.
X-ray Structure Determination of 5·MeOH41
Crystal Data: C15H23NO6: M = 313.34 gmol–1, orthorhombic,
a = 6.620(2) Å, b = 8.511(1) Å, c = 27.425(4) Å, V = 1545.1(5) Å3,
z = 4, space group P212121, μ = 0.87 mm–1, F(000) = 672,
MS (ESI): m/z (%) = 282.2 ([M + H]+, 100), 304.2 ([M + Na]+, 67).
Synthesis 2012, 44, 1385–1397
© Georg Thieme Verlag Stuttgart · New York

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Diglycosylated Indoles
1389
ESI-HRMS: m/z calcd for [C14H19NO5 + Na]+: 304.1161; found:
304.1158.
ESI-HRMS: m/z calcd for [C20H23NO7 + Na]+: 412.1372; found:
412.1382.
Acetylation of N-Glycosylindolines and N-Glycosylindoles;
General Procedure
A solution of the reactant in pyridine and Ac2O was stirred at r.t. for
16 h and then concentrated in vacuo.
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)indoline
The title compound was prepared according to the general proce-
dure from 7 (1.67 g, 5.96 mmol), Ac2O (9.01 mL, 95.3 mmol), and
pyridine (25 mL). The crude product was purified by flash chroma-
tography (eluent: cyclohexane–EtOAc, 1:1) to give the title com-
pound (6.12 g, 95%); colourless solid; mp 120–121 °C; Rf = 0.58
(cyclohexane–EtOAc, 1:1); [α]D22 +7.4 (c = 1.00, CHCl3).
1-(2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl)indole (9)
The title compound was prepared according to the general proce-
dure from 1-(β-D-galactopyranosyl)indole (411 mg, 1.47 mmol),
Ac2O (2.2 mL, 2.3 mmol), and pyridine (6 mL). The crude product
was purified by flash chromatography (eluent: cyclohexane–EtO-
Ac, 2:1) to give 9 (603 g, 92%); colourless solid; mp 114.5–116 °C;
IR (ATR): 3483, 2957, 1752, 1607, 1490, 1427, 1368, 1229, 1097,
1035, 910, 752 cm–1.
1H NMR, COSY, HSQC (400 MHz, CDCl3): δ = 7.06–7.10 (m, 2
22
3
4
H, H-4ind, H-6ind), 6.74 (d-pseudo-t, Japp,5,6/4 = 7.4 Hz, J5,7 = 0.9
Hz, 1 H, H-5ind), 6.55 (d, 3J7,6 = 7.8 Hz, 1 H, H-7ind), 5.34 (pseudo-
t, 3Japp,3,2/4 = 9.3 Hz, 1 H, H-3glc), 5.30 (pseudo-t, 3Japp,2,1/3 = 9.3 Hz,
1 H, H-2glc), 5.09 (pseudo-t, 3Japp,4,3/5 = 9.6 Hz, 1 H, H-4glc), 5.01 (d,
Rf = 0.49 (cyclohexane–EtOAc, 1:2); [α]D +10.2 (c = 1.00,
CHCl3).
IR (ATR): 2917, 1750, 1461, 1370, 1223, 1087, 1057, 921, 745
cm–1.
3
3
3J1,2 = 8.7 Hz, 1 H, H-1glc), 4.25 (dd, J6a/6b = 12.3 Hz, J6a/5 = 4.7
Hz, 1 H, H-6aglc), 4.03 (dd, 3J6b/6a = 12.3 Hz, 3J6b/5 = 2.4 Hz, 1 H, H-
6bglc), 3.76 (ddd, 3J5/4 = 10.0 Hz, 3J5/6a = 4.7 Hz, 3J5/6b = 2.4 Hz, 1 H,
H-5glc), 3.54–3.65 (m, 2 H, H2-2ind), 2.90–3.03 (m, 2 H, H2-3ind),
2.04, 2.03, 2.00, 1.99 (4 s, each 3 H, COCH3).
1H NMR, COSY, NOESY, HSQC (500 MHz, CDCl3): δ = 7.58 (d,
3J4,5 = 7.8 Hz, 1 H, H-4ind), 7.45 (d, 3J7,6 = 8.2 Hz, 1 H, H-7ind), 7.25
(d, 3J2,3 = 3.4 Hz, 1 H, H-2ind), 7.22 (ddd, 3J6,7 = 8.2 Hz, 3J6,5 = 7.1
Hz, 4J6,4 = 1.0 Hz, 1 H, H-6ind), 7.12 (ddd, 3J5,4 = 7.8 Hz, 3J5,6 = 7.1
Hz, J5,7 = 1.0 Hz, 1 H, H-5ind), 6.55 (d, 3J3,2 = 3.4 Hz, 1 H, H-3ind),
13C NMR (101 MHz, CDCl3): δ = 170.8, 170.4, 169.8, 169.7
(4 × C=O), 149.5 (C-7aind), 130.7 (C-3aind), 127.2 (C-6ind), 125.1
(C-4ind), 119.6 (C-5ind), 107.8 (C-7ind), 84.4 (C-1glc), 74.1 (C-3glc),
73.4 (C-5glc), 68.9 (C-2glc), 68.6 (C-4glc), 62.1 (C-6glc), 45.9 (C-2ind),
28.3 (C-3ind), 20.9, 20.81, 20.77 (2 C), (4 × COCH3).
MS (ESI): m/z (%) = 450.1 ([M + H]+, 100), 472.0 [M + Na]+, 22).
ESI-HRMS: m/z calcd for [C22H27NO9 + Na]+: 472.1584; found:
3
3
5.72 (dd, J2,3 = 10.2 Hz, J2,1 = 9.1 Hz, 1 H, H-2gal), 5.55 (d,
3J1,2 = 9.1 Hz, 1 H, H-1gal), 5.54 (dd, 3J4,3 = 3.4 Hz, 3J4,5 = 0.7 Hz,
1 H, H-4gal), 5.26 (dd, 3J3,2 = 10.2 Hz, J3,4 = 3.4 Hz, 1 H, H-3gal),
3
4.09–4.21 (m, 3 H, H-5gal, H-6a,bgal), 2.23, 2.01, 1.99, 1.65 (4 s,
each 3 H, COCH3).
13C NMR, DEPT, HSQC (126 MHz, CDCl3): δ = 170.6, 170.3,
170.2, 168.9 (4 × C=O), 136.2 (C-7aind), 129.3 (C-3aind), 125.0 (C-
2ind), 122.5 (C-6ind), 121.5 (C-4ind), 120.8 (C-5ind), 110.0 (C-7ind),
104.2 (C-3ind), 84.1 (C-1gal), 73.5 (C-5gal), 71.7 (C-3gal), 68.2 (C-
2gal), 67.4 (C-4gal), 61.6 (C-6gal), 20.9, 20.8, 20.7, 20.3
(4 × COCH3).
MS (FAB): m/z (%) = 331.2 ([M – indole]+, 100), 447.2 ([M]+, 75).
FAB-HRMS: m/z calcd for [C22H25NO9 + H]+: 448.1608; found:
472.1600.
1-(2,3,4,6-Tetra-O-acetyl-α/β-D-mannopyranosyl)indoline
The title compound was prepared according to the general proce-
dure from 8 (5.73 g, 19.3 mmol), Ac2O (26 mL, 0.275 mol) and pyr-
idine (52 mL). The crude product was purified by flash
chromatography (eluent: cyclohexane–EtOAc, 3:1) to give the title
compound as a mixture of anomers (α/β = 1:1.7, 6.6 g, 95%); co-
lourless oil; Rf = 0.13(α)/0.16(β) (cyclohexane–EtOAc, 3:1).
448.1590.
Anal. Calcd for C22H25NO9: C, 59.06; H, 5.63; N, 3.13. Found: C,
59.10; H, 5.77; N, 3.13.
MS (ESI): m/z (%) = 450.1 ([M + H]+, 100), 472.1 ([M + Na]+, 27).
HRMS-ESI: m/z calcd for [M + Na]+: 472.1584; found: 472.1562.
1-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)indole (10)
The title compound was prepared according to the general proce-
dure from 1-(β-L-fucopyranosyl)indole (2.69 g, 10.2 mmol), Ac2O
(11.6 mL, 10.2 mmol), and pyridine (32 mL). The crude product
was purified by flash chromatography (eluent: cyclohexane–EtO-
Ac, 4:1) to give 10 (3.72 g, 93%); yellow foam; Rf = 0.69 (cyclo-
hexane–EtOAc, 1:1); [α]D22 +3.0 (c = 1.00, CH2Cl2).
Oxidation of N-Glycosylindolines; General Procedure
A solution of the glycopyranosylindoline and DDQ in 1,4-dioxane
was stirred at r.t. until TLC indicated full conversion. After addition
of sat. aq NaHCO3 (100 mL) and extraction with EtOAc (3–7 × 30
mL), the combined organic layers were dried (Na2SO4) and concen-
trated in vacuo.
IR (ATR): 2988, 2939, 1750, 1464, 1368, 1311, 1237, 1089, 1064,
923 cm–1.
1-(β-D-Galactopyranosyl)indole
The title compound was prepared according to the general proce-
dure from 5 (1.52 g, 5.42 mmol) and DDQ (1.48 g, 6.51 mmol) in
1,4-dioxane (250 mL). Reaction time: 16 h. The residue was puri-
fied by flash chromatography (eluent: cyclohexane–EtOAc, 40:1)
to afford the title compound (1.46 g, 97%); colourless foam;
1H NMR, COSY (400 MHz, CDCl3): δ = 7.60 (d-pseudo-t,
3
3J4,5 = 7.9 Hz, 4Japp,4,3/6 = 1.0 Hz, 1 H, H-4ind), 7.47 (dd, J7,6 = 8.3
Hz, 3J7,5 = 0.8 Hz, 1 H, H-7ind), 7.28 (d, 3J2,3 = 3.4 Hz, 1 H, H-2ind),
7.23 (ddd, 3J6,7 = 8.3 Hz, 3J6,5 = 7.1 Hz, 4J6,4 = 1.3 Hz, 1 H, H-6ind),
7.13 (ddd, 3J5,4 = 7.9 Hz, 3J5,6 = 7.1 Hz, 4J5,7 = 1.1 Hz, 1 H, H-5ind),
22
Rf = 0.31 (CHCl3–MeOH–AcOH, 5:1:0.1); [α]D +1.8 (c = 1.00,
MeOH).
IR (ATR): 3420, 2912, 1610, 1483, 1407, 1251, 1078, 1025 cm–1.
3
4
6.56 (dd, J3,2 = 3.4 Hz, J3,4 = 0.6 Hz, 1 H, H-3ind), 5.71 (dd,
3J2,3 = 10.1 Hz, 3J2,1 = 9.1 Hz, 1 H, H-2fuc), 5.54 (d, 3J1,2 = 9.1 Hz, 1
H, H-1fuc), 5.40 (dd, 3J4,3 = 3.4 Hz, 3J4,5 = 1.0 Hz, 1 H, H-4fuc), 5.27
(dd, 3J3,2 = 10.1 Hz, 3J3,4 = 3.4 Hz, 1 H, H-3fuc), 4.09 (qd, 3J5,6 = 6.4
1H NMR (500 MHz, DMSO-d6): δ = 7.64 (dd, J7,6 = 8.2 Hz,
3
3
Hz, J5,4 = 1.0 Hz, 1 H, H-5fuc), 2.28, 2.01, 1.66 (3 s, each 3 H,
4J7,5 = 1.0 Hz, 1 H, H-7ind), 7.55 (ddd, 3J4,5 = 7.8 Hz, 4J4,6 = 1.1 Hz,
COCH3), 1.26 (d, 3J6,5 = 6.4 Hz, 3 H, H-6fuc).
3
1 H, H-4ind), 7.44 (d, J2,3 = 3.3 Hz, 1 H, H-2ind), 7.13 (ddd,
4J6,7 = 8.2 Hz, 3J6,5 = 7.1 Hz, 4J6,4 = 1.1 Hz, 1 H, H-6ind), 7.04 (ddd,
13C NMR, HSQC (400 MHz, CDCl3): δ = 170.7, 170.3, 169.0
(3 × C=O), 136.2 (C-7aind), 129.3 (C-3aind), 125.1 (C-2ind), 122.3
(C-6ind), 121.4 (C-4ind), 120.6 (C-5ind), 110.0 (C-7ind), 104.0 (C-3ind),
84.0 (C-1fuc), 72.1 (C-5fuc), 72.0 (C-3fuc), 70.5 (C-4fuc), 68.3 (C-2fuc),
20.9, 20.8, 20.4 (3 × COCH3), 16.4 (C-6fuc).
3
4
3J5,4 = 7.8 Hz, J5,6 = 7.1 Hz, J5,7 = 1.0 Hz, 1 H, H-5ind), 6.45 (dd,
2J3,2 = 3.3 Hz, 4J3,4 = 0.6 Hz, 1 H, H-3ind), 5.34 (d, 3J1,2 = 9.0 Hz, 1
H, H-1gal), 4.39 (br s, 4 H, OH), 4.11 (pseudo-t, Japp = 9.1 Hz, 1 H,
3
3
H-2gal), 3.82 (dd, J4,3 = 2.6 Hz, J4,5 = 1.0 Hz, 1 H, H-4gal), 3.70
(ddd, 3J5,6b = 6.6 Hz, 3J5,6a = 5.7 Hz, 3J5,4 = 1.0 Hz, 1 H, H-5gal), 3.5–
MS (ESI): m/z (%) = 412.13 ([M + Na]+, 26), 428.12 ([M + K]+, 14).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397

1390
C. Wiebe et al.
PAPER
3.60 (m, 2 H, H-3gal, H-6agal), 3.49 (dd, 3J6b,6a = 11.0 Hz, 3J6b,5 = 6.6
ESI-HRMS: m/z calcd for [C22H25NO9 + Na]+: 470.1427; found:
470.1422.
Hz, 1 H, H-6bgal).
13C NMR (101 MHz, DMSO-d6): δ = 135.8 (C-7aind), 128.6 (C-
3aind), 126.9 (C-2ind), 121.0 (C-6ind), 120.3 (C-4ind), 119.5 (C-5ind),
111.4 (C-7ind), 101.2 (C-3ind), 86.1 (C-1gal), 77.7 (C-5gal), 74.3 (C-
3ind), 68.9 (C-2ind), 68.6 (C-4ind), 60.6 (C-6ind).
1-(2,3,4,6-Tetra-O-acetyl-α-D-mannopyranosyl)indole (12) and
1-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)indole (13)
The title compounds were prepared according to the general proce-
dure from 1-(2,3,4,6-tetra-O-acetyl-α/β-D-mannopyranosyl)in-
doline (2.05 g, 4.57 mmol) and DDQ (1.25 g, 5.48 mmol) in 1,4-
dioxane (170 mL). Reaction time: 16 h. The residue was purified by
flash chromatography (eluent: cyclohexane–EtOAc, 5:1 → 4:1) to
afford 12 and 13.
MS (FAB): m/z (%) = 279.1 ([M]+, 100), 280.1 ([M + H]+, 75).
FAB-HRMS: m/z calcd for [C14H17NO5]+: 279.1107; found:
279.1115; m/z calcd for [C14H17NO5 + H]+: 280.1185; found:
280.1188.
12
1-(β-L-Fucopyranosyl)indole
Yield: 0.64 g (31%); colourless oil; Rf = 0.68 (cyclohexane–EtOAc,
The title compound was prepared according to the general proce-
dure from 6 (5.02 g, 18.9 mmol) and DDQ (5.15 g, 22.7 mmol) in
1,4-dioxane (350 mL). Reaction time: 16 h. The residue was puri-
fied by flash chromatography (eluent: cyclohexane–EtOAc, 1:1 →
1:2) to afford the title compound (2.93 g, 59%); reddish foam;
1:1); [α]D22 +90.4 (c = 1.00, CH2Cl2).
IR (ATR): 2960, 1746, 1469, 1368, 1311, 1220, 1117, 1050, 979,
915, 745 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.63 (mc, 2 H, H-4ind, H-7ind), 7.48
22
(d, J2,3 = 3.4 Hz, 1 H, H-2ind), 7.15–7.26 (m, 2 H, H-5ind, H-6ind),
3
Rf = 0.58 (CHCl3–MeOH–AcOH, 5:1:0.1); [α]D –10.7 (c = 1.00,
CH2Cl2).
6.64 (d, J = 3.4 Hz, 1 H, H-3ind), 6.07 (pseudo-t, 3Japp,2,1/3 = 2.9 Hz,
1 H, H-2man), 5.97 (d, J1,2 = 2.6 Hz, 1 H, H-1man), 5.49 (dd,
3
IR (ATR): 3374, 2888, 1682, 1608, 1517, 1457, 1368, 1307, 1223,
1163, 1082, 1000, 908 cm–1.
3J3,4 = 9.1 Hz, 3J3,2 = 3.2 Hz, 1 H, H-3man), 5.40 (t, 3Japp,4,3/5 = 8.9 Hz,
1 H, H-4man), 4.39 (dd, J6a,6b = 12.3 Hz, J6a,5 = 6.2 Hz, 1 H, H-
2
3
1H NMR (400 MHz, CDCl3): δ = 7.59 (d, 3J = 7.7 Hz, 1 H), 7.45 (d,
3J = 8.2 Hz, 1 H) (H-4ind, H-7ind), 7.18–7.22 (m, 2 H, H-2ind, H-
5/6ind), 7.13 (t, 3J = 7.4 Hz, 1 H, H-5/6ind), 6.47 (d, 3J = 3.2 Hz, 1 H,
6aman), 4.05 (dd, J6b,6a = 12.3 Hz, J6a,5 = 2.6 Hz, 1 H, H-6bman),
2
3
3
3
3
3.67 (ddd, J5,4 = 8.6 Hz, J5,6b = 6.2 Hz, J5,6a = 2.6 Hz, 1 H, H-
5man), 2.18, 2.11, 2.05, 2.04 (4 s, each 3 H, COCH3).
3
H-3ind), 4.89 (d, J1,2 = 8.9 Hz, 1 H, H-1fuc), 4.00 (pseudo-t,
13C NMR (75 MHz, CDCl3): δ = 170.7, 170.6, 170.0, 169.7
(4 × C=O), 136.7 (C-7aind), 129.3 (C-3aind), 125.1 (C-2ind), 122.8
(C-6ind), 121.21, 121.19 (C-4ind, C-5ind), 111.9 (C-7ind), 104.7 (C-
3ind), 82.2 (C-1man), 70.8 (C-5man), 70.3 (C-3man), 67.8 (C-2man), 66.0
(C-4man), 61.7 (C-6man), 20.91, 20.86, 20.84, 20.79 (4 × COCH3).
3Japp,2,1/3 = 9.2 Hz, 1 H, H-2fuc), 3.42 (q, 3J5,6 = 6.4 Hz, 1 H, H-5fuc),
3
3
3.35 (d, J4,3 = 2.9 Hz, 1 H, H-4fuc), 3.15 (dd, J3,2 = 9.4 Hz,
3J3,4 = 2.9 Hz, 1 H, H-3fuc), 1.16 (d, 3J6,5 = 6.4 Hz, 3 H, H-6fuc).
13C NMR (75 MHz, CDCl3): δ = 136.1 (C-7aind), 129.3 (C-3aind),
125.9 (C-2ind), 122.3 (C-6ind), 121.2 (C-4ind), 120.7 (C-5ind), 111.0
MS (ESI): m/z (%) = 331.0 ([M − indole]+, 12), 448.2 ([M + H]+,
(C-7ind), 103.0 (C-3ind), 86.0 (C-1fuc), 74.6, 73.0, 71.6, 69.8 (C-2fuc
C-3fuc, C-4fuc, C-5fuc), 16.4 (C-6fuc).
,
35), 470.1 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C22H25NO9 + Na]+: 470.1427; found:
470.1431.
MS (ESI): m/z (%) = 264.0 ([M + H]+, 81), 286.0 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C14H17NO4 + H]+: 264.1236; found:
264.1244.
13
Yield: 1.08 g (53%); colourless oil; Rf = 0.62 (cyclohexane–EtOAc,
1:1); [α]D22 +5.7 (c = 1.00, CH2Cl2).
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)indole (11)
The title compound was prepared according to the general proce-
dure from 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indoline
(2.36 g, 5.24 mmol) and DDQ (1.43 g, 6.29 mmol) in 1,4-dioxane
(160 mL). Reaction time: 16 h. The residue was purified by flash
chromatography (eluent: cyclohexane–EtOAc, 8:1) to afford 11
(2.21 g, 94%); colourless solid; mp 133–138 °C; Rf = 0.60 (cyclo-
hexane–EtOAc, 1:1); [α]D22 +0.5 (c = 1.00, CH2Cl2).
IR (ATR): 2956, 1743, 1521, 1460, 1364, 1315, 1209, 1105, 1052,
968, 915, 734 cm–1.
3
1H NMR (300 MHz, CDCl3): δ = 7.59 (d, J4,5 = 7.8 Hz, 1 H, H-
3
4ind), 7.40 (d, J7,6 = 8.2 Hz, 1 H, H-7ind), 7.20–7.26 [m, 2 H, this
multiplet contains: 7.25 (d, 3J2,1 = 3.4 Hz, 1 H, H-2ind), H-6ind], 7.13
3
(mc, 1 H, H-5ind), 6.52 (d, J3,2 = 3.4 Hz, 1 H, H-3ind), 5.85 (d,
3J1,2 = 1.0 Hz, 1 H, H-1man), 5.58 (dd, 3J2,3 = 3.0 Hz, 3J2,1 = 1.1 Hz,
1 H, H-2man), 5.42 (pseudo-t, 3Japp,4,3/5 = 10.0 Hz, 1 H, H-4man), 5.32
IR (ATR): 2939, 1743, 1523, 1457, 1379, 1315, 1230, 1220, 1089,
1035, 919, 902, 820, 753, 728 cm–1.
3
3
(dd, J3,4 = 10.0 Hz, J3,2 = 3.0 Hz, 1 H, H-3man), 4.34 (dd,
1H NMR, COSY, HSQC (400 MHz, CDCl3): δ = 7.60 (d-pseudo-t,
3J6b,5 = 5.9 Hz, J6a,6b = 12.3 Hz, 1 H, H-6aman), 4.23 (dd,
2
4
3
3J4,5 = 7.9 Hz, Japp,4,3/6 = 0.9 Hz, 1 H, H-4ind), 7.41 (dd, J7,6 = 8.4
Hz, 4J7,5 = 0.9 Hz, 1 H, H-7ind), 7.25 (ddd, 3J6,7 = 8.4 Hz, 3J6,5 = 7.1
Hz, 4J6,4 = 1.3 Hz, 1 H, H-6ind), 7.23 (d, 3J2,3 = 3.4 Hz, 1 H, H-2ind),
7.15 (ddd, 3J5,4 = 7.9 Hz, 3J5,6 = 7.1 Hz, 4J5,7 = 0.9 Hz, 1 H, H-5ind),
6.57 (d, 3J3,2 = 3.4 Hz, 1 H, H-3ind), 5.64 (d, 3J1,2 = 9.2 Hz, 1 H, H-
1glc), 5.55 (pseudo-t, 3Japp,2,1/3 = 9.2 Hz, 1 H, H-2glc), 5.45 (pseudo-t,
3Japp,3,2/4 = 9.3 Hz, 1 H, H-3glc), 5.29 (dd, 3J4,5 = 10.0 Hz, 3J4,3 = 9.4
Hz, 1 H, H-4glc), 4.30 (dd, 3J6a,6b = 12.4 Hz, 3J6a,5 = 4.9 Hz, 1 H, H-
6aglc), 4.15 (dd, 3J6b,6a = 12.4 Hz, 3J6b,5 = 2.3 Hz, 1 H, H-6bglc), 4.00
2J6b,6a = 12.3 Hz, 3J6a3,5 = 2.4 Hz, 1 H, H-6bman), 3.97 (ddd, 3J5,4 = 9.4
Hz, J5,6a = 5.9 Hz, J5,6b = 2.4 Hz, 1 H, H-5man), 2.11, 2.10, 2.03,
3
2.00 (4 s, each 3 H, COCH3).
13C NMR (75 MHz, CDCl3): δ = 170.8, 170.2, 169.8, 169.6 (4 ×
C=O), 135.3 (C-7aind), 128.8 (C-3aind), 125.2 (C-2ind), 122.3 (C-
6ind), 121.3 (C-4ind), 120.7 (C-5ind), 110.0 (C-7ind), 103.5 (C-3ind),
82.4 (C-1man), 75.5 (C-5man), 71.5 (C-3man), 69.6 (C-2man), 65.7 (C-
4man), 62.7 (C-6man), 20.90, 20.87, 20.7 (4 × COCH3).
MS (ESI): m/z (%) = 448.2 ([M + H]+, 59), 470.1 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C22H25NO9 + Na]+: 470.1427; found:
3
3
3
(ddd, J5,4 = 10.0 Hz, J5,6a = 4.9 Hz, J5,6b = 2.3 Hz, 1 H, H-5glc),
2.08, 2.07, 2.03, 1.67 (4 s, each 3 H, COCH3).
13C NMR, HSQC (101 MHz, CDCl3): δ = 170.8, 170.3, 169.6,
168.9 (4 × C=O), 136.3 (C-7aind), 129.2 (C-3aind), 124.5 (C-2ind),
122.5 (C-6ind), 121.5 (C-4ind), 120.9 (C-5ind), 109.7 (C-7ind), 104.5
(C-3ind), 83.3 (C-1glc), 74.7 (C-5glc), 73.5 (C-3glc), 70.5 (C-2glc), 68.3
(C-4glc), 62.0 (C-6glc), 20.9, 20.8 (2 C), 20.3 (4 × COCH3).
470.1429.
Diglycosylindoles; General Procedure
A cooled solution of the monoglycosylated indole and the glycosyl
trichloroacetimidate donor in anhyd CH2Cl2 was stirred for 2 h with
activated 4 Å molecular sieves. After the addition of BF3OEt2, stir-
ring was continued for the indicated time and the mixture was al-
ESI-MS: m/z (%) = 331.0 ([M − indole]+, 100), 448.2 ([M + H]+,
63), 470.1 ([M + Na]+, 44).
Synthesis 2012, 44, 1385–1397
© Georg Thieme Verlag Stuttgart · New York

PAPER
Diglycosylated Indoles
1391
lowed to warm until TLC indicated full conversion or formation of
side products. The mixture was filtered, diluted with CH2Cl2 (20
mL), the organic layer washed with sat aq NaHCO3 (2 × 10 mL) and
dried (Na2SO4). Evaporation of the solvent in vacuo gave a crude
product, which was purified by silica gel flash chromatography. If
the residue still contained impurities, it was further purified by
HPLC. For a similar procedure, see: reference 20.
6ind), 7.14 (pseudo-t, 3Japp = 7.5 Hz, 1 H, H-5ind), 6.03 (dd,3J1,2 = 3.1
4
3
Hz, J1,2(ind) = 1.4 Hz, 1 H, H-1man), 5.70 (dd, J2,3 = 10.1 Hz,
3J2,1 = 9.1 Hz, 1 H, H-2fuc), 5.57 (dd, 3J2,3 = 10.1 Hz, 3J2,1 = 3.1 Hz,
1 H, H-2man), 5.48 (d, 3J1,2 = 9.0 Hz, 1 H, H-1fuc), 5.39–5.44 (m, 3 H,
H-3man, H-4man, H-4fuc), 5.25 (dd, 3J3,2 = 10.4 Hz, 3J3,4 = 3.1 Hz, 1 H,
2
3
H-3fuc), 4.20 (dd, J6a,6b = 12.2 Hz, J6a,5 = 5.8 Hz, 1 H, H-6aman),
4.11 (dq, J5,6 = 6.4 Hz, J5,4 = 1.0 Hz, 1 H, H-5fuc), 4.05 (dd,
3
3
2J6b,6a = 12.2 Hz, 3J6b2,5 = 2.1 Hz, 1 H, H-6bman), 3.57 (ddd, 2J5,4 = 9.8
Hz, J5,6a = 5.7 Hz, J5,6b = 2.1 Hz, 1 H, H-5man), 2.36, 2.24, 2.05,
2
1-(2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl)-3-(2,3,4,6-tet-
ra-O-acetyl-α-D-mannopyranosyl)indole (16)
3
2.04, 2.00, 2.00, 1.53 (7 s, each 3 H, COCH3), 1.32 (d, J6,5 = 6.4
The title compound was prepared according to the general proce-
dure from 1-(3,4,5,6-tetra-O-acetyl-β-D-galactopyranosyl)indole
(9; 50 mg, 0.112 mmol), 2,3,4,6-tetra-O-acetyl-α-D-mannopyrano-
syl trichloroacetimidate (14; 83 mg, 0.168 mmol), molecular sieves
(2.0 g, 4 Å), and BF3OEt2 (10 μL, 80 μmol) in CH2Cl2 (6 mL). The
reaction mixture was cooled to –60 °C and allowed to warm to 0 °C
within 4.5 h. The residue was purified by flash chromatography (el-
uent: cyclohexane–EtOAc, 5:1 → 1:1) to afford 16 (48 mg, 55%);
Hz, 3 H, H-6fuc).
13C NMR, HSQC, HMBC (101 MHz, CDCl3): δ = 171.0, 170.9,
170.8, 170.7, 170.4, 170.1, 168.6 (7 × C=O), 136.4 (C-7aind), 127.2
(C-3aind), 124.6 (C-2ind), 123.3 (C-6ind), 121.1 (C-4ind), 121.0 (C-
5ind), 111.4 (C-3ind), 110.1 (C-7ind), 84.1 (C-1fuc), 73.6 (C-4fuc), 72.3
(C-5fuc), 71.7 (C-4man), 70.9 (C-2man), 70.7 (C-5man), 70.4 (C-3fuc),
69.9 (C-1man), 68.7 (C-2fuc), 66.4 (C-3man), 62.9 (C-6man), 21.3, 20.97
(2C), 20.95, 20.84, 20.79, 20.0 (7 × COCH3), 16.5 (C-6fuc).
20
colourless oil; Rf = 0.30 (cyclohexane–EtOAc, 1:1); [α]D +36.8
MS (ESI): m/z (%) = 742.2 ([M + Na]+, 100), 758.2 ([M + K]+, 15).
(c = 1.00, CHCl3).
ESI-HRMS: m/z calcd for [C34H41NO16 + Na]+: 742.2323; found:
742.2322.
IR (ATR): 3062, 2982, 2939, 2853, 1746, 1467, 1370, 1211, 1039,
911, 741 cm–1.
1H NMR, COSY, HSQC, HMBC (400 MHz, CDCl3): δ = 7.80 (dd,
1-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-3-(2,3,4,6-tetra-
O-acetyl-α-D-mannopyranosyl)indole (18)
4
3
3J4,5 = 8.0 Hz, J4,6 = 1.0 Hz, 1 H, H-4ind), 7.53 (dd, J7,6 = 8.2 Hz,
4J7,5 = 1.0 Hz, 1 H, H-7ind), 7.44 (d, J = 1.0 Hz, 1 H, H-2ind), 7.26
(ddd, 3J6,7 = 8.2 Hz, 3J6,5 = 7.0 Hz, 4J6,4 = 1.0 Hz, 1 H, H-6ind), 7.14
(ddd, 3J5,4 = 8.0 Hz, 3J5,6 = 7.0 Hz, 4J5,7 = 1.0 Hz, 1 H, H-5ind), 5.94
(dd, 3J2,3 = 2.8 Hz, 3J2,1 = 1.9 Hz, 1 H, H-2man), 5.70 (dd, 3J2,3 = 10.2
The title compound was prepared according to the general proce-
dure from 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole (11;
268 mg, 0.599 mmol), 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl
trichloroacetimidate (14; 443 mg, 0.898 mmol), molecular sieves
(3.3 g, 4 Å), and BF3OEt2 (50 μL, 400 μmol) in CH2Cl2 (10 mL).
The reaction mixture was cooled to –15 °C and allowed to warm to
8 °C within 4.5 h. The residue was purified by flash chromatogra-
phy (eluent: cyclohexane–EtOAc, 3:1 → 2:1 → 1.5:1) and subse-
quently preparative HPLC [tR = 40–53 min, gradient: n-hexane–i-
PrOH (97:3, in 20 min 80:20), flow 50 mL/min] to afford 18 (138
mg, 48%). The product contains about 10 mol% of 1-(2,3,4,6-tetra-
O-acetyl-β-D-glucopyranosyl)-3-acetylindole as a side product (de-
Hz, J2,1 = 8.9 Hz, 1 H, H-2gal), 5.56 (dd, J4,3 = 3.3 Hz, J4,5 = 0.9
Hz, 1 H, H-4gal), 5.51 (d, J1,2 = 8.9 Hz, 1 H, H-1gal), 5.34–5.40 (m, 3
H, H-1man, H-4man, H-3man), 5.25 (dd, 3J3,2 = 10.2 Hz, 3J3,4 = 3.3 Hz,
1 H, H-3gal), 3.99–4.21 (m, 5 H, H-5gal, H-6a,bgal, H-6a,bman), 3.55–
3.60 (m, 1 H, H-5man), 2.31, 2.20, 2.04, 2.03, 2.02, 1.99, 1.95, 1.70
(8 s, each 3 H, COCH3).
3
3
13C NMR, DEPT, HSQC, HMBC (126 MHz, CDCl3): δ = 171.0,
170.75, 170.73, 170.71, 170.5, 170.3, 169.8, 168.7 (8 × C=O),
136.3 (C-7aind), 127.6 (C-3aind), 124.5 (C-2ind), 123.5 (C-6ind), 121.3
(C-5ind), 121.2 (C-4ind), 111.6 (C-3ind), 111.3 (C-7ind), 85.4 (C-1gal),
73.5 (2C, C-1man, C-5gal), 71.5 (C-3gal), 70.9, 70.8 (C-3man, C-5man),
69.6 (C-2man), 68.4 (C-2gal), 67.2 (C-4gal), 66.4 (C-4man), 62.8, 61.7
(C-6man, C-6gal), 21.3, 21.03, 21.00, 20.97, 20.95, 20.91, 20.8, 20.3
(8 × COCH3).
1
termined by H NMR spectroscopy); colourless oil; Rf = 0.25 (cy-
clohexane–EtOAc, 1:1); [α]D20 +45.9 (c = 1.00, CHCl3).
IR (ATR): 3297, 2985, 2940, 2359, 1743, 1603, 1522, 1430, 1379,
1245, 1230, 1170, 1090, 919, 833, 813 cm–1.
3
1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J4,5 = 7.9 Hz, 1 H, H-
3
4
4ind), 7.47 (dt, J7,6 = 8.4 Hz, J7,5 = 0.9 Hz, 1 H, H-7ind), 7.42 (d,
MS (ESI): m/z (%) = 778.3 ([M + H]+, 100), 800.2 ([M + Na]+, 90),
3J = 1.4 Hz, 1 H, H-3ind), 7.29 (d-pseudo-t, J6,5/7 = 7.4 Hz,
3
816.2 ([M + K]+, 45).
4J6,4 = 0.8 Hz, 1 H, H-6ind), 7.16 (ddd, 3J5,4 = 7.9 Hz, 3J5,6 = 7.1 Hz,
ESI-HRMS: m/z calcd for [C36H43NO18 + H]+: 778.2553; found:
778.2551; m/z calcd for [C36H43NO18 + Na]+: 800.2372; found:
800.2377; m/z calcd for [C36H43NO18 + K]+: 816.2117; found:
816.2131.
4J5,7 = 0.8 Hz, 1 H, H-5ind), 5.94 (dd, J2,3 = 2.9 Hz, J2,1 = 1.9 Hz,
3
3
1 H, H-2man), 5.60 (d, J1,2 = 8.8 Hz, 1 H, H-1glc), 5.55 (pseudo-t,
3
3J2,1/3 = 9.1 Hz, 1 H, H-2glc), 5.44 (pseudo-t, 3J3,/4 = 9.2 Hz, 1 H, H-
3glc), 5.42–5.31 (m, 4 H, H-1man, H-3man, H-4man, H-4glc), 4.29 (dd,
2J6a,6b = 12.5 Hz, J6a,5 = 4.3 Hz, 1 H, H-6aglc), 4.22–4.27 (m, 2 H,
3
H-6aman, H-6bman), 4.07 (dd, J6b,6a = 12.4 Hz, J6a,5 = 2.4 Hz, 1 H,
2
3
1-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-3-(2,3,4,6-tetra-O-
acetyl-α-D-mannopyranosyl)indole (17)
H-6bglc), 3.98–4.04 (m, 1 H, H-5gal), 3.60 (ddd, J5,4 = 8.9 Hz,
3
The title compound was prepared according to the general proce-
dure from 1-(2,3,4-tri-O-acetyl-β-L-fucopyranosyl)indole (10; 100
mg, 0.257 mmol), 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl tri-
chloroacetimidate (14; 190 mg, 0.386 mmol), molecular sieves (1.6
g, 4 Å), and BF3OEt2 (20 μL, 160 μmol) in CH2Cl2 (13 mL). The
reaction mixture was cooled to –15 °C and allowed to warm to
10 °C within 4.5 h. The residue was purified by flash chromatogra-
phy (eluent: cyclohexane–EtOAc, 4:1 → 2:1) to afford the title
compound (59.3 mg, 32%); colourless foam; Rf = 0.37 (cyclohex-
ane–EtOAc, 1:1); [α]D22 +41.8 (c = 1.00, CH2Cl2).
3J5,6a = 5.7 Hz, 3J5,6b = 2.4 Hz, 1 H, H-5man), 2.22, 2.12, 2.08, 2.06,
2.05, 2.02, 1.96, 1.68 (8 s, each 3 H, COCH3).
13C NMR (101 MHz, CDCl3): δ = 170.90, 170.86, 170.67, 170.56,
170.3, 169.7, 169.5, 168.6 (8 × C=O), 136.3 (C-7aind), 127.5 (C-
3aind), 123.8 (C-2ind), 123.5 (C-6ind), 121.3 (C-5ind), 121.2 (C-4ind),
111.6 (C-3ind), 110.7 (C-7ind), 84.3 (C-1glc), 74.9 (C-5glc), 73.4 (C-
3glc), 73.2 (C-1man), 70.87, 70.82, 70.80 (C-2glc, C-3man, C-5man), 69.5
(C-2man), 68.1 (C-4glc), 66.5 (C-4man), 62.8 (C-6glc), 62.0 (C-6man),
21.2, 20.9, 20.84 (2 C), 20.80, 20.74, 20.71, 20.1 (8 × COCH3).
MS (ESI): m/z (%) = 490.3 [1-(β-D-glc(OAc)4-3-acetylindole],
IR (ATR): 2988, 2942, 1743, 1460, 1364, 1223, 1085, 1052, 919,
742 cm–1.
1H NMR, COSY, HSQC, HMBC (400 MHz, CDCl3): δ = 7.81 (d,
3J4,5 = 8.0 Hz, 1 H, H-4ind), 7.57 (d, J = 1.4 Hz, 1 H, H-2ind), 7.48 (d,
3J7,6 = 8.3 Hz, 1 H, H-7ind), 7.27 (pseudo-t, 3Japp = 7.5 Hz, 1 H, H-
795.2 ([M + NH4]+, 100), 800.3 ([M + Na]+, 55).
ESI-HRMS: m/z calcd for [C36H43NO18 + Na]+: 800.2378; found:
800.2390.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397

1392
C. Wiebe et al.
PAPER
1-(2,3,4,6-Tetra-O-acetyl-α-D-mannopyranosyl)-3-(2,3,4,6-tet-
ra-O-acetyl-α-D-mannopyranosyl)indole (19)
(dd, 3J2,3 = 3.2 Hz, 3J2,1 = 1.7 Hz, 1 H, H-23-man), 5.87 (d, 3J1,2 = 1.4
Hz, 1 H, H-11-man), 5.54 (dd, 3J2,3 = 3.2 Hz, 3J2,1 = 1.4 Hz, 1 H, H-
21-man), 5.49 (t, 3J4,3/4 = 10.1 Hz, 1 H, H-41-man), 5.41 (t, 3J4,3/4 = 10.0
Hz, 1 H, H-43-man), 5.34 (dd, 3J3,4 = 10.1 Hz, 3J3,2 = 3.2 Hz, 1 H, H-
The title compound was prepared according to the general proce-
dure from 1-(3,4,5,6-tetra-O-acetyl-α-D-mannopyranosyl)indole
(12; 307 mg, 0.686 mmol), 2,3,4,6-tetra-O-acetyl-α-D-mannopy-
ranosyl trichloroacetimidate (14; 505 mg, 0.686 mmol), molecular
sieves (1.5 g, 4 Å), and BF3OEt2 (80 μL, 640 μmol) in CH2Cl2 (6
mL). The reaction mixture was cooled to –15 °C and allowed to
warm to 7 °C within 4 h. The residue was purified by flash chroma-
tography (eluent: cyclohexane–EtOAc, 6:1 → 5:1) and subsequent-
ly by preparative HPLC [tR = 62–73 min, gradient: n-hexane–i-
PrOH (97:3, in 60 min 87:13, in 70 min 80:20), flow 50 mL/min] to
afford 19 (85 mg, 16%); colourless oil; Rf = 0.28 (cyclohexane–
EtOAc, 1:1); [α]D22 +59.2 (c = 1.00, CDCl3).
3
3
31-man/H-33-man), 5.32 (dd, J3,4 = 10.1 Hz, J3,2 = 3.2 Hz, 1 H, H-
31-man/H-33-man), 4.26–4.35 (m, 2 H, H-61-man), 4.23 (dd, 2J6a/6b = 12.2
3
2
Hz, J6a,5 = 5.7 Hz, 1 H, H-6a3-man), 4.02 (dd, J6b/6a = 12.2 Hz,
3J6b/5 = 2.2 Hz, 1 H, H-6b3-man), 3.98 (ddd, 3J5/4 = 10.1 Hz, 3J5/6 = 4.7
3
3
Hz, J5/6a = 3.0 Hz, 1 H, H-51-man), 3.62 (ddd, J5/4 = 10.1 Hz,
3J5/6a = 5.7 Hz, 3J5/6b = 2.2 Hz, 1 H, H-53-man), 2.22, 2.13, 2.11, 2.06,
2.04, 2.04, 2.00, 1.99 (8 s, each 3 H, COCH3).
13C NMR, HSQC, HMBC (101 MHz, CDCl3): δ = 170.8, 170.7,
170.6, 170.4, 170.1, 169.7, 169.64, 169.60 (8 × C=O), 135.8 (C-
7aind), 127.0 (C-3aind), 124.0 (C-2ind), 123.3 (C-6ind), 121.0 (C-5ind),
120.8 (C-4ind), 111.0 (C-3ind), 110.1 (C-7ind), 82.1 (C-11-man), 75.4
(C-51-man), 73.3 (C-13-man), 71.3, 71.0 (C-31-man, C-33-man), 70.5 (C-
53-man), 69.4, 69.3 (C-21-man, C-23-man), 66.2, 65.4 (C-41-man, C-43-man),
62.6, 62.5 (C-61-man, C-63-man), 21.0, 20.83, 20.76, 20.75, 20.74,
20.71, 20.59, 20.58 (8 × COCH3).
MS (ESI): m/z (%) = 795.5 ([M + NH4]+, 100), 800.4 ([M + Na]+,
35).
ESI-HRMS: m/z calcd for [C36H43NO18 + Na]+: 800.2378; found:
800.2352.
IR (ATR): 3291, 2980, 2942, 2361, 1740, 1600, 1520, 1431, 1387,
1244, 1233, 1169, 1091, 923, 830, 809 cm–1.
3
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J4,5 = 7.9 Hz, 1 H, H-
4
3
4ind), 7.63 (d, J2, 1(3-man) = 1.0 Hz, 1 H, H-2ind), 7.60 (d, J7,6 = 8.3
Hz, 1 H, H-7ind), 7.28 (mc, 1 H, H-6ind), 7.17 (pseudo-t, 3J5,6/4 = 7.5
Hz, 1 H, H-5ind), 6.00–6.02 (m, 2 H, H-11-man, H-23-man), 5.92 (dd,
3J2,3 = 5.6 Hz, 3J2,1 = 3.3 Hz, 1 H, H-21-man), 5.49–5.53 (m, 2 H, H-
31-man, H-33-man), 5.44 (pseudo-t, J1,2/2(ind) = 1.5 Hz, 1 H, H-13-man),
3
5.40 (pseudo-t, J4,3/5 = 9.7 Hz, 1 H, H-43-man), 5.25 (dd, J4,5 = 6.6
3
3
Hz, J4,3 = 5.7 Hz, 1 H, H-41-man), 4.69 (dd, J6a,6b = 12.2 Hz,
3
2
3J6a,5 = 7.6 Hz, 1 H, H-6a1-man), 4.24 (dd, J6a,6b = 12.2 Hz,
2
1-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)-3-(2,3,4,6-tet-
ra-O-acetyl-β-D-mannopyranosyl)indole (20b)
3J6a,5 = 5.8 Hz, 1 H, H-6a3-man), 4.12 (dd, J6b,6a = 12.2 Hz,
2
3J6b,5 = 3.4 Hz, 1 H, H-6b1-man), 4.10 (dd, J6b,6a = 12.2 Hz,
2
Yield: 81 mg (10%); colourless oil, Rf = 0.27 (cyclohexane–EtOAc,
3J6b,5 = 2.3 Hz, 1 H, H-6b3-man), 4.02 (ddd, 3J5,4 = 7.7 Hz, 3J5,6a = 5.6
1:1); [α]D22 –12.2 (c = 1.00, CH2Cl2).
Hz, J5,6b = 3.4 Hz, 1 H, H-51-man), 3.66 (ddd, J5,4 = 9.5 Hz,
3J5,6a = 5.8 Hz, 3J5,6b = 2.3 Hz, 1 H, H-53-man), 2.23 (s, 3 H), 2.18 (s,
3 H), 2.17 (s, 3 H), 2.08 (s, 3 H), 2.05 (s, 6 H), 1.99 (s, 3 H), 1.92 (s,
3 H), (8 × COCH3).
3
3
1H NMR, COSY, NOESY, HSQC, HMBC (400 MHz, CDCl3):
δ = 7.64 (d, 3J4,5 = 7.9 Hz, 1 H, H-4ind), 7.32 (d, 3J7,6 = 8.3 Hz, 1 H,
H-7ind), 7.26 (s, 1 H, H-2ind), 7.21 (ddd, 3J6,7 = 8.3 Hz, 3J6,5 = 7.1 Hz,
4J6,4 = 1.2 Hz, 1 H, H-6ind), 7.10–7.16 (m, 1 H, H-5ind), 5.82 (d,
3J1,2 = 1.2 Hz, 1 H, H-11-man), 5.48 (mc, 2 H, H-21-man, H-23-man),
5.35–5.41 (m, 2 H, H-41-man, H-43-man), 5.30 (mc, 2 H, H-31-man, H-
33-man), 5.05 (br s, 1 H, H-13-man), 4.19–4.34 (m, 4 H, H-6a,b1-man, H-
13C NMR (101 MHz, CDCl3): δ = 170.9, 170.8, 170.7, 170.4, 169.9,
169.8, 169.6, 169.3 (8 × C=O), 136.9 (C-7aind), 127.3 (C-3aind),
124.1 (C-2ind), 123.6 (C-6ind), 121.4 (C-5ind), 121.0 (C-4ind), 111.9
(C-3ind), 111.5 (C-7ind), 80.0 (C-11-man), 73.4 (C-13-man), 73.2 (C-51-
man), 71.0 (C-53-man), 70.5 (C-33-man), 70.0 (C-23-man), 69.0 (C-31-man),
67.7 (C-21-man), 66.9 (C-41-man), 66.6 (C-43-man), 62.8 (C-63-man), 60.9
(C-61-man), 21.3, 21.0, 20.92, 20.89 (4C), 20.6 (8 × COCH3).
3
3
3
6a,b3-man), 3.95 (ddd, J5,4 = 9.8 Hz, J5,6 = 6.1 Hz, J5,6 = 2.3 Hz,
1 H, H-51-man/H-53-man), 3.84 (ddd, J5,4 = 9.8 Hz, J5,6 = 5.7 Hz,
3J5,6 = 2.7 Hz, 1 H, H-51-man/H-53-man), 2.10 (s, 3 H), 2.09 (s, 6 H),
2.08 (s, 3 H), 2.02 (s, 3 H), 1.98 (s, 6 H), 1.92 (s, 3 H), (8 × COCH3).
3
3
MS (ESI): m/z (%) = 800.4 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C36H43NO18 + Na]+: 800.2378; found:
13C NMR (101 MHz, CDCl3): δ = 170.7, 170.6, 170.3, 170.02,
169.99, 169.9, 169.7, 169.5 (8 × C=O), 134.9 (C-7aind), 126.1 (C-
3aind), 123.6 (C-2ind), 122.7 (C-6ind), 120.7 (C-5ind), 119.9 (C-4ind),
800.2349.
112.2 (C-3ind), 109.6 (C-7ind), 81.7 (C-11-man), 76.6, 75.4 (C-51-man
,
1-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)-3-(2,3,4,6-tet-
ra-O-acetyl-α/β-D-mannopyranosyl)indole (20a,b)
C-53-man), 73.8 (C-13-man), 72.4, 71.1 (C-31-man, C-33-man), 70.6, 69.2
(C-21-man, C-23-man), 66.3, 65.4 (C-41-man, C-43-man), 63.2, 62.6 (C-
61-man, C-63-man), 20.8 (2 C), 20.75, 20.73, 20.70, 20.6 (3 C),
(8 × COCH3).
The title compound was prepared according to the general proce-
dure from 1-(3,4,5,6-tetra-O-acetyl-β-D-mannopyranosyl)indole
(13; 460 mg, 1.03 mmol), 2,3,4,6-tetra-O-acetyl-α-D-mannopy-
ranosyl trichloroacetimidate (14; 599 mg, 1.22 mmol), molecular
sieves (1.5 g, 4 Å), and BF3OEt2 (100 μL, 800 μmol) in CH2Cl2
(6 mL). The reaction mixture was cooled to –20 °C and allowed to
warm to 10 °C within 4 h. The residue was purified by flash chro-
matography (eluent: cyclohexane–EtOAc, 2:1 → 1.5:1) and subse-
quently by preparative HPLC (tRα = 66–70 min, tRβ = 70–78 min,
gradient: n-hexane–i-PrOH (97:3, in 60 min 85:15, in 70 min
50:50), Flow 50 mL/min] to afford compound 20a (α) (28 mg, 4%)
and compound 20b (β) (81 mg, 10%) and a mixture of anomers (89
mg, 11%, α/β = 1:2.3).
MS (ESI): m/z (%) = 795.5 ([M + NH4]+, 100), 800.4 ([M + Na]+,
32).
ESI-HRMS: m/z calcd for [C36H43NO18 + Na]+: 800.2378; found:
800.2339.
3-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-1-(2,3,4,6-tetra-O-
acetyl-β-D-galactopyranosyl)indole (21)
The title compound was prepared according to the general proce-
dure from 1-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)indole
(9; 50 mg, 0.112 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl tri-
chloroacetimidate (15; 72 mg, 0.168 mmol), molecular sieves (2.0
g, 4 Å), and BF3OEt2 (10 μL, 80 μmol) in CH2Cl2 (4 mL). The re-
action mixture was cooled to –60 °C and allowed to warm 0 °C
within 4.5 h. The residue was purified by flash chromatography (el-
uent: cyclohexane–EtOAc, 3:1 → 1:1) to afford 21 (40 mg, 33%);
1-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)-3-(2,3,4,6-tet-
ra-O-acetyl-α-D-mannopyranosyl)indole (20a)
Yield: 28 mg (4%); colourless oil, Rf = 0.27 (cyclohexane–EtOAc,
1:1); [α]D22 +23.8 (c = 1.00, CH2Cl2).
20
colourless oil; [α]D +3.5 (c = 1.00, CHCl3); Rf = 0.38 (cyclohex-
1H NMR, COSY, NOESY, HSQC, HMBC (400 MHz, CDCl3):
ane–EtOAc, 2:1).
3
4
δ = 7.80 (dt, J4,5 = 8.0 Hz, J4,6 = 1.0 Hz, 1 H, H-4ind), 7.59 (d,
4J = 1.4 Hz, 1 H, H-2ind), 7.43 (d, 3J7,6 = 8.4 Hz, 1 H, H-7ind), 7.27
(ddd, 3J6,7 = 8.4 Hz, 3J6,5 = 7.1 Hz, 4J6,4 = 1.2 Hz, 1 H, H-6ind), 7.15
(ddd, 3J5,4 = 8.0 Hz, 3J5,6 = 7.1 Hz, 4J5,7 = 0.9 Hz, 1 H, H-5ind), 5.96
IR (ATR): 3057, 2981, 2940, 2857, 1743, 1468, 1369, 1212, 1041,
916, 744 cm–1.
Synthesis 2012, 44, 1385–1397
© Georg Thieme Verlag Stuttgart · New York

PAPER
Diglycosylated Indoles
1393
1H NMR, COSY, HSQC, HMBC (400 MHz, CDCl3): δ = 7.68 (d,
3J4,5 = 7.9 Hz, 1 H, H-4ind), 7.38 (d, 3J7,6 = 8.2 Hz, 1 H, H-7ind), 7.31
13C NMR (101 MHz, CDCl3): δ (characteristic signals) = 170.5,
170.3, 169.7, 169.2, 162.7 (C=O), 77.9, 72.4, 70.8, 69.6, 69.4, 68.7,
66.2, 57.8, 16.0, 15.7.
3
3
4
(s, 1 H, H-2ind), 7.22 (ddd, J6,7 = 8.2 Hz, J6,5 = 7.1 Hz, J6,4 = 1.1
Hz, 1 H, H-6ind), 7.14 (ddd, 3J5,4 = 7.9 Hz, 3J5,6 = 7.1 Hz, 4J5,7 = 1.1
Hz, 1 H, H-5ind), 5.50–5.61 (4 H, H-2fuc, H-3fuc, H-1gal, H-2gal), 5.37
MS (ESI): m/z (%) = 662.3 ([M + H]+, 57), 684.2 ([M + Na]+, 58).
3
3
(dd, J4,3 = 3.4 Hz, J4,5 = 0.8 Hz, 1 H, H-4gal), 5.18–5.24 (m, 2 H,
H-4fuc, H-3gal), 4.73 (d, 3J1,2 = 9.8 Hz, 1 H, H-1fuc), 4.09–4.21 (m, 3
H, H-5gal, H-6a,bgal), 3.99 (dq, 3J5,6 = 6.4 Hz, 3J5,4 = 1.0 Hz, 1 H, H-
5fuc), 2.26, 2.24, 2.02 (3 s, each 3 H, COCH3), 1.98 (s, 6 H,
2 × COCH3), 1.77, 1.65 (2 s, each 3 H, COCH3), 1.23 (d, 3J6,5 = 6.4
Hz, 3 H, H-6fuc).
ESI-HRMS: m/z calcd for [C32H39NO14 + Na]: 684.2268; found:
684.2272.
3-(2,3,4-Tri-O-acetyl-α/β-L-fucopyranosyl)-1-(2,3,4,6-tetra-O-
acetyl-β-D-glucopyranosyl)indole (23)
The title compound was prepared according to the general proce-
dure from 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole (11;
310 mg, 0.698 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl trichlo-
roacetimidate (15; 450 mg, 1.04 mmol), molecular sieves (2.8 g, 4
Å), and BF3OEt2 (60 mL, 480 μmol) in CH2Cl2 (10 mL). The reac-
tion mixture was cooled to –15 °C and allowed to warm to 8 °C
within 4.5 h. The residue was purified by flash chromatography (el-
uent: cyclohexane–EtOAc, 3:1) to afford the title compound as an
anomeric mixture (141 mg, 45%, α/β = 1:1.8, determined by NMR
spectroscopy); colourless oil, Rf = 0.43 (cyclohexane–EtOAc, 1:1).
13C NMR, DEPT, HSQC, HMBC (101 MHz, CDCl3): δ = 171.0,
170.62, 170.57, 170.4, 170.3, 169.6, 168.8 (7 × C=O), 136.8 (C-
3aind), 127.9 (C-7aind), 123.3 (C-3ind), 123.0 (C-6ind), 121.0 (C-5ind),
120.1 (C-4ind), 114.3 (C-3ind), 110.1 (C-7ind), 83.9 (C-1gal), 74.5 (C-
1fuc), 73.7 (C-5gal), 73.4 (C-5fuc), 73.3 (C-3gal), 71.8 (C-4fuc), 71.4 (C-
4gal), 69.6 (C-2fuc), 68.5 (C-3fuc), 67.5 (C-2gal), 61.7 (C-6gal), 21.0,
20.94, 20.92, 20.87, 20.80, 20.77, 20.33 (7 × COCH3), 16.9 (C-
6fuc).
MS (ESI): m/z (%) = 742.2 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C34H41NO16 + Na]+: 742.2318; found:
IR (ATR): 3060, 2981, 2942, 2857, 1746, 1468, 1372, 1212, 1039,
915, 742 cm–1.
742.2312.
1H NMR (400 MHz, CDCl3): δ (anomeric mixture) = 7.80 (d,
J = 7.9 Hz, 1 H, H-4indα), 7.71 (d, J = 7.8 Hz, 1.8 H, H-4indβ), 7.49
(s, 1 H, H-2indα), 7.40 (d, J = 8.3 Hz, 1 H, H-7indα), 7.35 (d, J = 8.2
Hz, 1.8 H, H-7indβ), 7.23–7.34 (m, 4.6 H, H-2indβ, H-6indα/β), 7.16 (t,
J = 7.5 Hz, 2.8 H, H-5indα/β), 5.20–5.76 (m, 12.6 H, H-1glcα/β, H-
2glcα/β, H-3glcα/β, H-4glcα/β, H-1fucα, H-2fucα/β, H-3fucα/β, H-4fucα/β), 4.71
(d, J = 9.8 Hz, 1.8 H, H-1fucβ), 4.29 (dd, 2J6a,6b = 12.4 Hz, 3J6a,5 = 4.9
Hz, 1 H, H-6amanα), 4.28 (dd, 2J6a,6b = 12.5 Hz, 3J6a,5 = 5.0 Hz, 1.8 H,
H-6aglcβ), 4.19 (dd, 2J6b,6a = 12.4 Hz, 3J6b,5 = 2.1 Hz, 1 H, H-6bglcα),
1-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-3-(2,3,4-tri-O-acetyl-
α/β-L-fucopyranosyl)indole (22)
The title compound was prepared according to the general proce-
dure from 1-(2,3,4-tri-O-acetyl-β-L-fucopyranosyl)indole (10; 100
mg, 0.257 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl trichloro-
acetimidate (15; 167 mg, 0.386 mmol), molecular sieves (1.6 g, 4
Å), and BF3OEt2 (20 μL, 160 μmol) in CH2Cl2 (13 mL). The reac-
tion mixture was cooled to –15 °C and allowed to warm to 10 °C
within 4.5 h. The residue was purified by flash chromatography (el-
uent: cyclohexane–EtOAc, 3:1 → 1.5:1) to afford 22 as a mixture
of anomers (40 mg, 24%, α/β = 1:2). The anomeric ratio was deter-
mined by 1H NMR spectroscopy: δ = 4.68 (d, 3J1,2 = 9.9 Hz, 2 H, H-
4.12 (dd, J6b,6a = 12.5 Hz, J6b,5 = 2.0 Hz, 1.8 H, H-6bglcβ), 5.20–
5.77 (m, 4.6 H, H-5fucβ, H-5glcα/β), 3.60 (dq, 3J5,6 = 6.4 Hz, 3J5,4 = 1.2
Hz, 1 H, H-5fucα), 2.26 (s, 5.4 H), 2.21 (s, 3 H), 2.09 (s, 3 H), 2.08
(s, 6 H), 2.07 (s, 8.4 H), 2.06 (s, 5.4 H), 2.03 (s, 8.4 H), 1.99 (s, 5.4
H), 1.76 (s, 5.4 H), 1.69 (s, 5.4 H), 1.62 (s, 3 H), 1.25 (s, 3 H,
COCH3), 1.24 (d, 3J6,5 = 6.3 Hz, 1.8 H, H-6fucβ), 1.04 (d, 3J6,5 = 6.4
Hz, 4 H, H-6fucα).
2
3
13-fucβ), 4.57 (d, J1,2 = 7.8 Hz, 1 H, H-13-fucα); colourless oil;
Rf = 0.35 (cyclohexane–EtOAc, 1:1).
3
Major Anomer: 1-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-3-
(2,3,4-tri-O-acetyl-β-L-fucopyranosyl)indole
Major Anomer: 3-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-1-
(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole
3
1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J4,5 = 7.9 Hz, 1 H, H-
13C NMR (101 MHz, CDCl3): δ = 170.9, 170.7, 170.5, 170.3 (2 C),
169.6, 168.8 (7 × C=O), 136.8 (C-7aind), 127.6 (C-3aind), 123.0 (C-
2ind), 122.8 (C-6ind), 121.0 (C-4ind), 120.1 (C-5ind), 114.4 (C-7ind),
109.7 (C-3ind), 82.9 (C-1glc), 74.8 (C-5glc), 74.5 (C-1fuc), 73.5 (C-
3glc), 73.2 (C-5fuc), 73.0 (C-3fuc), 71.3 (C-4fuc), 70.5 (C-2glc), 69.4 (C-
2fuc), 68.2 (C-4glc), 62.1 (C-6glc), 21.0, 20.9, 20.8, 20.7 (2 C), 20.6,
20.2 (7 × COCH3), 16.8 (C-6fuc).
4ind), 7.43 (d, 3J7,6 = 8.3 Hz, 1 H, H-7ind), 7.30 (s, 1 H, H-2ind), 7.23
(ddd, 3J6,7 = 8.3 Hz, 3J6,5 = 7.0 Hz, 4J6,4 = 1.2 Hz, 1 H, H-6ind), 7.16
(ddd, 3J5,4 = 7.9 Hz, 3J5,6 = 7.0 Hz, 4J5,7 = 1.0 Hz, 1 H, H-5ind), 5.66
3
3
(dd, J2,3 = 10.1 Hz, J2,1 = 9.2 Hz, 1 H, H-21-fuc), 5.60 (pseudo-t,
Japp = 9.9 Hz, 1 H, H-23-fuc), 5.48 (d, J1,2 = 9.1 Hz, 1 H, H-11-fuc),
3
5.38 (dt, J4,3 = 3.4 Hz, J4,5 = 1.1 Hz, 2 H, H-41-fuc, H-43-fuc), 5.25
3
3
3
3
(dd, J3,2 = 10.2 Hz, J3,4 = 3.4 Hz, 1 H, H-31-fuc), 5.20 (dd,
3J3,2 = 10.1 Hz, 3J3,4 = 3.4 Hz, 1 H, H-33-fuc), 4.68 (d, 3J1,2 = 9.9 Hz,
1 H, H-13-fuc), 4.03 (qd, 3J5,6 = 6.4 Hz, 3J5,4 = 1.1 Hz, 1 H, H-51-fuc),
Minor Anomer: 3-(2,3,4-Tri-O-acetyl-α-L-fucopyranosyl)-1-
(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole
3.96 (qd, J5,6 = 6.3 Hz, J5,4 = 1.1 Hz, 1 H, H-53-fuc), 2.29, 2.28,
2.00, 1.99, 1.79, 1.66 (6 × COCH3), 1.23 (d, 3J6,5 = 6.2 Hz, 3 H, H-
63-fuc), 1.22 (d, 3J6,5 = 6.2 Hz, 3 H, H-61-fuc).
13C NMR (101 MHz, CDCl3): δ = 170.7, 170.5, 170.2 (2 C), 169.8,
169.4, 168.5 (7 × C=O), 136.1 (C-7aind), 128.4 (C-3aind), 124.0,
123.2 (C-2ind, C-6ind), 121.1, 121.0 (C-4ind, C-5ind), 111.6 (C-7ind),
109.7 (C-3ind), 83.4(C-1glc), 74.8, 73.0, 71.5, 70.3, 70.1, 69.0, 68.6,
68.2, 66.1 (9 × CHglc/fuc), 61.9 (C-6glc), 20.8, 19.9 (2 × COCH3),
16.2 (C-6fuc).
3
3
13C NMR (101 MHz, CDCl3): δ = 170.9, 170.7, 170.5, 170.3, 169.4,
169.0 (6 × C = O), 136.7 (C-7aind), 127.3 (C-3aind), 124.1 (C-2ind),
122.8 (C-6ind), 120.8 (C-5ind), 120.5 (C-4ind), 113.8 (C-3ind), 110.2
(C-7ind), 83.9 (C-11-fuc), 74.9 (C-13-fuc), 73.2 (C-33-fuc), 73.1 (C-53-
fuc), 72.2 (C-51-fuc), 72.9 (C-31-fuc), 71.4 (C-43-fuc), 70.5 (C-41-fuc),
69.3 (C-23-fuc), 68.3 (C-21-fuc), 21.0, 20.94, 20.88, 20.76, 20.71, 20.2
(6 × COCH3), 16.9, 16.4 (C-61-fuc, C-63-fuc).
MS (ESI): m/z (%) = 742.1 ([M + H]+, 100).
ESI-HRMS: m/z calcd for [C34H41NO16 + H]+: 742.2323; found:
742.2310.
3-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-1-(2,3,4,6-tetra-O-
acetyl-α-D-mannopyranosyl)indole (24)
Minor Anomer: 1-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-3-
(2,3,4-tri-O-acetyl-α-L-fucopyranosyl)indole
The title compound was prepared according to the general proce-
dure from 1-(3,4,5,6-tetra-O-acetyl-α-D-mannopyranosyl)indole
(12; 400 mg, 0.85 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl tri-
chloroacetimidate (15; 570 mg, 0.97 mmol), molecular sieves (1.5
g, 4 Å), and BF3OEt2 (80 μL, 640 μmol) in CH2Cl2 (6 mL). The re-
action mixture cooled to –20 °C and allowed to warm to 10 °C with-
1H NMR (400 MHz, CDCl3): δ (characteristic signals) = 7.37 (d,
J = 5.5 Hz, 1 H, H-13-fuc), 5.76 (t, J = 5.4 Hz, 1 H), 5.14–5.05 (m, 2
H), 4.98 (dd, J = 10.5 Hz, 3.4 Hz, 1 H), 4.57 (t, J = 7.7 Hz, 1 H),
4.15 (dd, J = 9.6 Hz, 5.2 Hz, 1 H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397

1394
C. Wiebe et al.
PAPER
in 4 h. The residue was purified by flash chromatography (eluent:
cyclohexane–EtOAc, 2:1 → 1:1) to afford 24; (220 mg, 36%); co-
lourless oil; Rf = 0.47 (cyclohexane–EtOAc, 1:1); [α]D22 +58.5 (c =
1.00, CH2Cl2).
FAB-HRMS: m/z calcd for [C42H41NO6S + Na]: 710.2552; found:
710.2525; m/z calcd for [C42H41NO6S + K]: 726.2292; found:
726.2302.
2-(2,3,4-Tri-O-benzyl-α-L-fucopyranosyl)-1H-indole (38)37
A solution of tosylindole 35 (340 mg, 0.494 mmol) and n-Bu4NF
(2.5 mL, 1 M in THF) in THF (7 mL) was heated to reflux for 5
days. The reaction mixture was quenched with sat. aq NaHCO3 (10
mL) and the resulting mixture was extracted with EtOAc (2 × 10
mL). The combined organic layers were dried (Na2SO4), and con-
centrated in vacuo. The crude product was purified by flash chroma-
tography (eluent: cyclohexane–EtOAc, 8:1) to give the title
compound (199 mg, 75%); colourless oil; Rf = 0.50 (cyclohexane–
EtOAc, 3:1); [α]D22 –69.8 (c = 1.00, CH2Cl2).
IR (ATR): 2999, 2940, 1739, 1457, 1360, 1220, 1082, 1049, 913,
740 cm–1.
1H NMR, COSY, HSQC, HMBC (400 MHz, CDCl3): δ = 7.82 (m,
1 H, H-4ind), 7.57 (m, 1 H, H-7ind), 7.52 (s, 1 H, H-2ind), 7.16–7.26
(m, 2 H, H-5ind, H-6ind), 6.01 (dd, 3J2,3 = 3.2 Hz, 3J2,1 = 2.6 Hz, 1 H,
3
H-2man), 5.93 (d, J1,2 = 2.6 Hz, 1 H, H-1man), 5.65 (pseudo-t,
2J2,1/3 = 9.9 Hz, 1 H, H-2fuc), 5.50 (dd, 3J3,2 = 3.2 Hz, 3J3,4 = 9.0 Hz,
3
3
1 H, H-3man), 5.41 (dd, J4,1 = 1.1 Hz, J4,3 = 3.3 Hz, 1 H, H-4fuc),
5.38 (pseudo-t, J4,3/5 = 8.9 Hz, 1 H, H-4man), 5.21 (dd, J3,2 = 10.1
Hz, 3J3,4 = 3.3 Hz, 1 H, H-3fuc), 4.71 (d, 3J1,2 = 9.7 Hz, 1 H, H-1fuc),
4.37 (dd, 2J6a,6b = 12.3 Hz, 3J6a,5 = 6.2 Hz, 1 H, H-6aman), 3.98–4.03
(m, 2 H, H-5fuc, H-6bman), 3.62 (ddd, 3J5,4 = 8.8 Hz, 3J5,6a = 6.2 Hz,
3J5,6b = 2.5 Hz, 1 H, H-5man), 2.31, 2.18, 2.11, 2.06, 2.01, 1.99, 1.75
(7 s, each 3 H, COCH3), 1.27 (d, 3J6,5 = 6.4 Hz, 3 H, H-6fuc).
3
3
1H NMR (400 MHz, CDCl3): δ = 8.88 (s, 1 H, NH), 7.52 (d,
3J4,5 = 7.7 Hz, 1 H, H-4ind), 7.22–7.37 (m, 16 H, HPh, H-7ind), 7.15–
7.19 (m, 1 H, H-6ind), 7.09–7.13 (m, 1 H, H-5ind), 6.52 (s, 1 H, H-
3ind), 5.34 (d, 3J1,2 = 5.0 Hz, 1 H, H-1fuc), 4.88 (d, 2J = 11.7 Hz, 1 H,
3
CH2Ph), 4.60–4.77 (m, 5 H, CH2Ph), 4.31 (dd, J2,3 = 9.3 Hz,
3J2,1 = 5.2 Hz, 1 H, H-2fuc), 3.85 (dq, 3J5,6 = 6.5 Hz, 3J5,4 = 2.0 Hz, 1
H, H-5fuc), 3.81 (dd, 1 H, 3J3,2 = 9.1 Hz, 3J3,4 = 2.9 Hz, 1 H, H-3fuc),
13C NMR, HSQC, HMBC (101 MHz, CDCl3): δ = 171.0, 170.7,
170.52, 170.47, 170.0, 169.7, 169.4 (7 × C=O), 137.1 (C-7aind),
127.4 (C-3aind), 124.0 (C-2ind), 123.4, 121.4 (C-5ind, C-6ind), 120.2
(C-4ind), 114.2 (C-3ind), 112.2 (C-7ind), 82.2 (C-1man), 74.8 (C-1fuc),
73.2 (C-5fuc), 73.0 (C-3fuc), 71.3 (C-4fuc), 70.8 (C-5man), 70.1 (C-
3man), 69.4 (C-2fuc), 67.7 (C-2man), 65.9 (C-4man), 61.7 (C-6man), 21.0,
20.92, 20.89 (2 C), 20.85, 20.7 (7 × COCH3), 16.9 (C-6fuc).
3
3
3.63 (pseudo-t, Japp,4,3/5 = 2.3 Hz, 1 H, H-4fuc), 1.20 (d, J6,5 = 6.5
Hz, 3 H, H-6fuc).
13C NMR (101 MHz, CDCl3): δ = 138.65, 138.62, 138.1 (3 × C-
1Ph), 135.83, 135.75 (C-7aind, C-2ind), 128.6 (2 C), 128.5 (2 C),
128.41 (2 C), 128.39 (2 C), 128.12 (2 C), 128.07 (11 × CHPh),
128.03 (C-3aind), 127.81, 127.79, 127.72 (2 C, 4 × CHPh), 121.7 (C-
6ind), 120.4 (C-4ind), 119.7 (C-5ind), 111.1 (C-7ind), 101.7 (C-3ind),
79.1 (C-1fuc), 77.8 (C-2fuc), 76.9 (C-4fuc), 74.4, 74.1, 73.1 (CH2Ph),
69.8 (2 C, C-1fuc, C-5fuc), 16.5 (C-6fuc).
MS (ESI): m/z (%) = 742.3 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C34H41NO6 + Na]+: 742.2323; found:
742.2313.
MS (ESI): m/z (%) = 534.1 ([M + H]+, 100).
ESI-HRMS: m/z calcd for [C35H35NO4 + Na]+: 556.2464; found:
2-(3,4,5-Tri-O-benzyl-α-L-fucopyranosyl)-1-(p-toluenesulfo-
nyl)-1H-indole (35)36,37
A solution of N-(p-toluenesulfonyl)-2-iodoaniline (33; 479 mg,
1.28 mmol), fucosylacetylene 31 (516 mg, 1.17 mmol), PPh3 (39
mg, 0.15 mmol), CuI (30 mg, 16 mmol), and Pd(OAc)2 (19 mg,
0.085 mmol) in Et3N (16 mL) and DMF (5 mL) was stirred at 70 °C
for 21 h. The mixture was diluted with EtOAc (150 mL) and washed
with sat. aq NaHCO3 (2 × 50 mL), and brine (50 mL), dried
(Na2SO4), and concentrated under reduced pressure. The crude
product was purified by flash chromatography (eluent: cyclohex-
ane–EtOAc, 15:1) to give 35 (345 mg, 70%); colourless oil;
556.2446.
3-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)-2-(2,3,4,6-tet-
ra-O-benzyl-α-D-galactopyranosyl)-1H-indole (40)
The title compound was prepared according to the general proce-
dure from 2-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-1H-in-
dole (37;37 31 mg, 32 μmol), 2,3,4,6-tetra-O-acetyl-α-D-manno-
pyranosyl trichloroacetimidate (14; 36 mg, 0.073 mmol), molecular
sieves (1.4 g, 4 Å), and BF3OEt2 (10 μL, 80 μmol) in CH2Cl2 (4
mL). The reaction mixture was cooled to –60 °C and allowed to
warm to 0 °C within 2 h. The residue was purified by flash chroma-
tography (eluent: cyclohexane–EtOAc, 3:1), and subsequently by
preparative HPLC (n-hexane–i-PrOH, 97:3) to afford 40 (7 mg,
23%); colourless oil; Rf = 0.3 (cyclohexane–EtOAc, 5:1).
22
Rf = 0.60 (cyclohexane–EtOAc, 3:1); [α]D –124.4 (c = 1.00,
CDCl3).
IR (ATR): 3031, 2922, 1597, 1596, 1453, 1369, 1210, 1174, 1149,
1092, 1071 747, 697 cm–1.
3
1H NMR (400 MHz, CDCl3): δ = 8.22 (d, J4,5 = 8.3 Hz, 1 H, H-
4ind), 7.55 (part of an AA′BB′-spin system, 2 H, H-3,5Ts), 7.45 (d,
J = 4.9 Hz, 1 H, H-7ind), 7.43 (m, 2 H), 7.17–7.36 (m, 15 H), 6.69–
IR (ATR): 3423, 3029, 2867, 1742, 1496, 1461, 1346, 1210, 1065,
741, 697, 516 cm–1.
6.99 (m, 2 H) (15 × HPh, H-5ind, H-6ind, H-2,6Ts), 6.86 (pseudo-t,
1H NMR, COSY, HSQC, NOESY, TOCSY (400 MHz, CDCl3):
3
J
3,1(fuc)/4(ind) = 1.0 Hz, 1 H, H-3ind), 5.78 (dd, J1,2 = 2.0 Hz,
δ = 9.04 (s, 1 H, NH), 7.90 (d, 3J4,5 = 8.0 Hz, 1 H, H-4ind), 7.22–7.38
4J1,3(ind) = 1.2 Hz, 1 H, H-1fuc), 4.82 (d, 2J = 12.2 Hz, 1 H, CH2Ph),
4.60 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.58 (d, J = 12.2 Hz, 1 H,
CH2Ph), 4.54 (d, 2J = 12.0 Hz, 1 H, CH2Ph), 4.29 (dd, 3J2,3 = 4.7 Hz,
3J2,1 = 2.2 Hz, 1 H, H-2fuc), 4.20–4.26 (m, 2 H, C-5fuc, CH2Ph), 4.18
(d, J = 12.0 Hz, 1 H, CH2Ph), 3.96 (dd, J4,5 = 5.5 Hz, J4,3 = 3.3
Hz, 1 H, H-4fuc), 3.90 (dd, 3J2,3 = 4.7 Hz, 3J3,4 = 3.3 Hz, 1 H, H-3fuc),
2.29 (s, 3 H, ArCH3), 1.37 (d, 3J6,5 = 6.9 Hz, 3 H, C-6fuc).
(m, 19 H, HPh), 7.08–7.16 (m, 3 H, H-6ind H-7ind, HPh), 7.04 (ddd,
,
2
2
3J5,4 = 8.0 Hz, J5,6 = 6.8 Hz, J5,7 = 1.4 Hz, 1 H, H-5ind), 5.51 (d,
3J1,2 = 3.8 Hz, 1 H, H-1gal), 5.44 (dd, 3J2,3 = 3.5 Hz, 3J2,1 = 1.2 Hz, 1
H, H-2man), 5.40 (t, 3J4,3/5 = 10.1 Hz, 1 H, H-4man), 5.36 (br s, 1 H,
H-1man), 5.17 (dd, 3J3,4 = 10.1 Hz, 3J3,2 = 3.5 Hz, 1 H, H-3man), 4.76
(d, 2J = 11.6 Hz, 1 H, CH2Ph), 4.74 (d, 2J = 12.0 Hz, 1 H, CH2Ph),
3
4
2
3
3
2
2
4.69 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.55 (d, J = 11.6 Hz, 1 H,
2
13C NMR (101 MHz, CDCl3): δ = 144.9 (C-4Ts), 138.8, 138.6,
138.2, 137.7, 137.6, (3 × C-1Ph, C-2ind, C-1Ts), 135.7 (C-7aind),
130.1 (C-3aind), 129.9 (2 C, C-3,5Ts), 128.5 (2 C), 128.4 (2 C),
128.33 (2 C), 128.29 (2C), 127.91 (2 C), 127.88, 127.77 (2 C),
127.72, 127.6 (15 × CHPh), 126.5 (2 C, C-2,6Ts), 124.6, 123.9 (C-
5ind, C-6ind), 120.9 (C-7ind), 115.4 (C-4ind), 112.6 (C-3ind), 75.9 (C-
2fuc), 75.3 (C-3fuc), 73.7 (C-4fuc), 73.5, 72.4, 71.7 (3 × CH2Ph), 71.2
(C-5fuc), 65.3 (C-1fuc), 21.7 (ArCH3), 14.2 (C-6fuc).
CH2Ph), 4.53 (d, J = 12.2 Hz, 1 H, CH2Ph), 4.47–4.50 (m, 2 H,
CH2Ph), 4.36 (br d, 2J = 11.0 Hz, 1 H, CH2Ph), 4.11–4.22 [m, 4 H,
3
3
this multiplet contains: 4.20 (dd, J6a,6b = 12.1 Hz, J6a,5 = 4.9 Hz,
1 H, H-6aman), 4.13 (dd, J6b,6a = 12.1 Hz, J6b,5 = 2.5 Hz, 1 H, H-
2
3
6bman), H-2gal, H-5gal)], 3.97 (dd, 3J4,5 = 3.9 Hz, 3J4,3 = 2.8 Hz, 1 H,
H-4gal), 3.92–3.95 (m, 1 H, H-6gal), 3.84 (dd, J3,2 = 7.3 Hz,
3
3J3,4 = 2.8 Hz, 1 H, H-3gal), 3.58–3.65 (m, 2 H, H-5man, H-6gal), 2.00
(s, 6 H), 1.90 (s, 3 H), 1.58 (s, 3 H) (4 × COCH3).
13C NMR, HSQC (101 MHz, CDCl3): δ = 170.9, 170.4, 170.2,
MS (ESI): m/z (%) = 726.7 ([M + K]+, 100).
170.0 (4 × C=O), 138.5, 138.4 (2 C), 137.8 (4 × C-1Ph), 135.4 (C-
Synthesis 2012, 44, 1385–1397
© Georg Thieme Verlag Stuttgart · New York

PAPER
Diglycosylated Indoles
1395
7aind), 131.4 (C-2ind), 128.7 (6 C), 128.6 (2 C), 128.3 (2 C), 128.2,
128.09 (2 C), 128.06 (2 C), 127.98 (3 C), 127.94, 127.85
(20 × CHPh), 127.0 (C-3aind), 122.2, 122.0 (C-4ind, C-6ind), 119.6 (C-
5ind), 111.0 (C-7ind), 100.2 (C-3ind), 78.7 (C-5gal), 76.7 (C-3gal), 76.2
(C-5man), 74.5 (C-1man), 74.3, 74.2 (H-4gal, H-2gal), 74.1, 73.5, 73.4,
72.9 (4 × CH2Ph), 72.5 (H-3man), 71.7 (C-2man), 68.4 (C-6man), 67.6
(C-1gal), 66.7 (C-4man), 63.4 (C-6gal), 21.0 (2 C), 20.9, 20.7
(4 × COCH3).
13C NMR (101 MHz, CDCl3): δ = 171.0, 170.5, 169.5 (3 × C=O),
138.5, 138.4, 138.3, 137.5 (4 × C-1Ph), 135.5 (C-7aind), 133.8 (C-
2ind), 128.62 (2 C), 128.61 (2 C), 128.58 (2 C), 128.50 (2 C), 128.42
(2 C), 128.3, 128.0, 127.9, 127.8 (4 C), 127.7 (2 C), 127.6
(20 × CHPh), 126.3 (C-3aind), 122.3 (C-6ind), 119.9 (C-6ind), 119.8
(C-5ind), 111.1 (C-7ind), 108.3 (C-3ind), 78.7 (C-2gal), 75.4 (C-5gal),
75.1 (C-3gal), 74.6 (C-1fuc), 73.7 (CH2Ph), 73.4 (C-5fuc), 73.3 (2 C,
2 × CH2Ph), 73.1 (C-3fuc), 72.9 (C-4gal), 72.1 (CH2Ph), 71.5 (C-4fuc),
69.3 (C-2fuc), 66.6 (C-6gal), 63.7 (C-1gal), 20.9, 20.8, 20.6
(3 × COCH3), 16.9 (C-6fuc).
FAB-HRMS: m/z calcd for [C56H59NO14 + H]+: 970.4008; found:
970.4007; m/z calcd for [C56H59NO14 + Na]+: 992.3828; found:
992.3835.
MS (ESI): m/z (%) = 912.7 ([M + H]+, 100).
As a side product, 3-acetyl-2-(2,3,4,6-tetra-O-benzyl-β-D-galacto-
pyranosyl)-1H-indole was isolated.
ESI-HRMS: m/z calcd for [C54H57NO12 + H]+: 912.3959; found:
912.3940.
3-Acetyl-2-(2,3,4,6-Tetra-O-benzyl-β-D-galactopyranosyl)-1H-
indole
3-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-2-(2,3,4-tri-O-benzyl-
α-L-fucopyranosyl)-1H-indole (42)
Yield: 9.0 mg (41%); colourless oil; Rf = 0.63 (cyclohexane–
The title compound was prepared according to the general proce-
dure from 2-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-1H-indole (38;
72 mg, 0.14 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl trichloro-
acetimidate (15; 88 mg, 0.20 mmol), molecular sieves (1.5 g, 4 Å),
and BF3OEt2 (20 μL, 160 μmol) in CH2Cl2 (4 mL). The reaction
mixture was cooled to –18 °C and allowed to warm to 0 °C within
2 h. The residue was purified by flash chromatography (eluent: cy-
clohexane–EtOAc, 3.5:1) to afford 42 (54 mg, 50%); colourless oil;
Rf = 0.65 (cyclohexane–EtOAc, 1:1); [α]D22 –31.5 (c = 1.00,
CH2Cl2).
EtOAc, 1:1); [α]D22 –36.1 (c = 1.00, CH2Cl2).
1H NMR, COSY, HSQC, HMBC (400 MHz, CDCl3): δ = 9.38 (s, 1
H, NH), 7.86 (d, J = 7.8 Hz, 1 H, H-4ind), 7.18–7.37 (m, 18 H, H-
5ind, H-6ind, H-7ind, 15 × HPh), 7.11 (mc, 1 H, HPh), 6.97 (mc, 2 H,
HPh), 6.65 (mc, 2 H, HPh), 5.79 (d, 3J1,2 = 1.6 Hz, 1 H, H-1gal), 4.87
(d, 2J = 12.4 Hz, 1 H, CH2Ph), 4.58 (d, 2J = 12.4 Hz, 1 H, CH2Ph),
3
4.46–4.54 (m, 5 H, H-5gal, 4 × CH2Ph), 4.37 (dd, J2,3 = 4.0 Hz,
2
3
3J2,1 = 1.6 Hz, 1 H, H-2gal), 4.26 (dd, J6a,6b = 12.0 Hz, J6a,5 = 9.2
Hz, 1 H, H-6agal), 4.10 (dd, J4,5 = 3.6 Hz, J4,3 = 3.1 Hz, 1 H, H-
3
3
4gal), 4.02 (d, 2J = 11.9 Hz, 1 H, CH2Ph), 3.87 (d, 2J = 11.9 Hz, 1 H,
1H NMR, COSY, ROESY, HSQC, HMBC (400 MHz, CD3CN):
δ = 9.51 (s, 1 H, NH), 7.78 (d, J = 7.7 Hz, 1 H, H-4ind), 7.25–7.44
(m, 14 H, 13 × HPh, H-7ind), 7.20 (s, 2 H, HPh), 7.12 (mc, 1 H, H-
6ind), 7.07 (mc, 1 H, H-5ind), 5.49–5.59 (m, 2 H, H-12-fuc, H-23-fuc),
CH2Ph), 3.83 (dd, J6b,6a = 12.0 Hz, J6a,5 = 1.9 Hz, 1 H, H-6bgal),
2
3
3.79 (dd, J3,2 = 3.8 Hz, J3,4 = 3.1 Hz, 1 H, H-3gal), 2.62 (s, 3 H,
3
3
COCH3).
3
3
5.31 (dd, J4,3 = 3.4 Hz, J4,5 = 0.8 Hz, 1 H, H-43-fuc), 5.16 (dd,
13C NMR, DEPT, HSQC, HMBC (101 MHz, CDCl3): δ = 194.2
(C=O), 145.4 (C-2ind), 138.7, 138.5, 138.4, 137.5 (4 × C-1Ph), 135.0
(C-3aind), 128.6 (2 C), 128.51 (2 C), 128.0 (3 C), 127.9, 127.8 (2 C),
127.7, 127.6 (20 × CHPh), 126.6 (C-7aind), 122.6 (C-5ind), 122.1 (C-
6ind), 120.7 (C-4ind), 113.1 (C-3ind), 112.0 (C-7ind), 76.1 (C-5gal), 74.5
(C-2gal), 73.6, 73.3 (2 × CH2Ph), 73.1 (C-3gal), 72.7 (C-4gal), 72.1,
71.4 (2 × CH2Ph), 66.0 (C-1gal), 65.9 (C-6gal), 31.3 (COCH3).
HRMS-FAB: m/z calcd for [C24H27NO10 + H]+: 682.3163; found:
682.3165; m/z calcd for [C24H27NO10 + Na]+: 704.2983; found:
704.2985.
3J3,2 = 10.1 Hz, 3J3,2 = 3.4 Hz, 1 H, H-33-fuc), 5.02 (d, 3J1,2 = 9.8 Hz,
1 H, H-13-fuc), 4.75 (s, 2 H, CH2Ph), 4.71 (d, J = 11.6 Hz, 1 H,
2
2
2
CH2Ph), 4.59 (d, J = 11.6 Hz, 1 H, CH2Ph), 4.56 (br d, J = 11.6
Hz, 1 H, CH2Ph), 4.42 (br d, 2J = 11.6 Hz, 1 H, CH2Ph), 3.98–4.03
(m, 4 H, H-22-fuc, H-32-fuc, H-52-fuc, H-53-fuc), 3.88 (mc, 1 H, H-42-fuc),
2.17, 1.91, 1.58 (3 s, each 3 H, COCH3), 1.40 (d, 3J6,5 = 6.7 Hz, 3 H,
H-62-fuc), 1.12 (d, 3J6,5 = 6.4 Hz, 3 H, H-63-fuc).
13C NMR, HSQC, HMBC (101 MHz, CD3CN): δ = 171.6, 171.0,
169.8 (3 × C=O), 140.0, 139.9, 139.1 (3 × C-1Ph), 136.3 (C-7aind),
135.2 (C-2ind), 129.4 (2 C), 129.3 (4 C), 129.1 (2 C), 128.8 (3 C),
128.7 (2 C), 128.6, 128.5 (15 × CHPh), 127.3 (C-3aind), 122.6 (C-
6ind), 120.8 (C-4ind), 120.2 (C-5ind), 112.3 (C-7ind), 110.3 (C-3ind),
78.9 (C-32-fuc), 77.5 (C-22-fuc), 76.0 (C-42-fuc), 74.3 (C-13-fuc), 74.0,
73.9 (C-33-fuc, CH2Ph), 73.5 (3 C, 2 × CH2Ph, C-52-fuc), 72.1 (C-43-
fuc), 71.1 (C-53-fuc), 70.4 (C-23-fuc), 66.5 (C-12-fuc), 20.9 (2 C), 20.8
(3 × COCH3), 17.0 (C-63-fuc), 15.4 (C-62-fuc).
MS (ESI): m/z (%) = 828.3 ([M + Na]+, 100), 1634.7 ([2 M + Na]+,
35).
ESI-HRMS: m/z calcd for [C47H51NO11 + Na]+: 828.3360; found:
828.3346.
3-(2,3,4-Tri-O-acetyl-α/β-L-fucopyranosyl)-2-(2,3,4,6-Tetra-O-
benzyl-β-D-galactopyranosyl)-1H-indole (41)
The title compound was prepared according to the general proce-
dure from 2-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)-1H-in-
dole (37;37 100 mg, 0.156 mmol), 2,3,4-tri-O-acetyl-α-L-
fucopyranosyl trichloroacetimidate (15; 138 mg, 0.317 mmol), mo-
lecular sieves (1.3 g, 4 Å), and BF3OEt2 (30 μL, 240 μmol) in
CH2Cl2 (4 mL). The reaction mixture was cooled to –47 °C and al-
lowed to warm to –8 °C within 2 h. The residue was purified by
flash chromatography (eluent: cyclohexane–EtOAc, 7:1), and sub-
sequently by preparative HPLC (n-hexane–i-PrOH, 97:3) to afford
41 (65 mg, 46%); colourless oil; Rf = 0.61 (cyclohexane–EtOAc,
1:1); [α]D22 +19.0 (c = 1.00, CH2Cl2).
3-(2,3,4,6-Tetra-O-acetyl-β-D-mannopyranosyl)-2-(2,3,4,6-tet-
ra-O-benzyl-β-D-glucopyranosyl)-1H-indole (43)
1H NMR (400 MHz, CDCl3): δ = 8.95 (s, 1 H, NH), 7.81 (d, J = 7.4
Hz, 1 H, H-4ind), 7.22–7.40 (m, 18 H, HPh), 7.08–7.19 (m, 3 H, H-
5ind, H-6ind, H-7ind), 7.03–7.07 (m, 2 H, HPh), 5.72 (pseudo-t,
3Japp,2,3 = 9.6 Hz, 1 H, H-2fuc), 5.49 (br s, 1 H, H-1gal), 5.39 (dd,
3J4,3 = 3.4 Hz, 3J4,5 = 0.7 Hz, 1 H, H-4fuc), 5.23 (dd, 3J3,2 = 10.1 Hz,
3J3,4 = 3.4 Hz, 1 H, H-3fuc), 4.75 (d, 2J = 12.4 Hz, 1 H, CH2Ph), 4.70
(d, 3J2,1 = 9.8 Hz, 1 H, H-1fuc), 4.54–4.64 (m, 4 H, CH2Ph), 4.50 (d,
2J = 12.0 Hz, 1 H, CH2Ph), 4.36–4.42 (m, 1 H, H-5gal), 4.23 (dd,
2J6a,6b = 11.3 Hz, 3J6a,5 = 7.5 Hz, 1 H, H-6agal), 4.19 (s, 2 H, CH2Ph),
4.17 (dd, 3J = 5.9 Hz, 3J = 2.7 Hz, 1 H, H-4gal), 3.94 (dd,
The title compound was prepared according to the general proce-
dure from 2-(3,4,5,6-tetra-O-benzyl-α-D-glucopyranosyl)-1H-in-
dole (39; 90 mg, 0.141 mmol), 2,3,4,6-tetra-O-acetyl-α-D-manno-
pyranosyl trichloroacetimidate (14; 107 mg, 0.212 mmol), molecu-
lar sieves (1.5 g, 4 Å), and BF3OEt2 (40 μL, 200 μmol) in CH2Cl2
(4 mL). The reaction mixture was cooled to –18 °C and allowed to
warm to 0 °C within 1 h. As TLC indicated little conversion, the re-
action mixture was cooled to –20 °C and more BF3OEt2 (20 μL,
160 μmol) was added. This procedure was repeated once more.
Then, the mixture was allowed to warm to –2 °C within another 1.5
h. The residue was purified by flash chromatography (eluent: cyclo-
hexane–EtOAc, 3:1) to afford 43 (46 mg, 34%); colourless oil;
3
2J6b,6a = 11.3 Hz, J6b,5 = 2.9 Hz, 1 H, H-6bgal), 3.84–3.91 (m, 3 H,
H-2gal, H-3gal, H-5fuc), 2.18 (br s, 3 H, COCH3), 2.01, 1.66 (2 s, each
3 H, COCH3), 1.21 (d, 3J6,5 = 6.4 Hz, 3 H, H-6fuc).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397

1396
C. Wiebe et al.
PAPER
22
Rf = 0.62 (cyclohexane–EtOAc, 1:1); [α]D +61.8 (c = 1.00,
CDCl3).
(2 C), 128.44, 128.3 (2 C), 128.12, 128.08 (2 C), 127.86, 127.81,
127.78 (2 C), (CHPh), 126.2 (C-3aind), 122.4 (C-6ind), 120.1 (2 C, C-
4ind, C-5ind), 111.3 (C-7ind), 109.7 (C-3Ind), 81.2 (C-3glc), 80.1 (C-
2glc), 77.1 (C-4glc), 74.4, 74.3 (2 × CH2Ph), 73.7, 73.6, 73.47, 73.43,
73.3, 73.1 (2 × CH2Ph, C-1fuc, C-3fuc, C-5fuc, C-5glc), 71.6 (C-4fuc),
69.0 (C-6fuc), 68.8 (C-2fuc), 68.6 (C-1glc), 21.0 (2 C), 20.7
(3 × COCH3), 16.8 (C-6fuc).
1H NMR (600 MHz, CDCl3): δ = 9.37 (s, 1 H, NH), 8.01 (d,
3J4,5 = 8.1 Hz, 1 H, H-4ind), 7.23–7.38 (m, 21 H, HPh, H-7ind), 7.14
(mc, 1 H, H-6ind), 7.07 (pseudo-t, Japp,5,4/6 = 7.5 Hz, 1 H, H-5ind),
3
5.62 (s, 1 H, H-1man), 5.54 (d, 3J1,2 = 5.6 Hz, 1 H, H-1glc), 5.45 (dd,
3J2,3 = 3.5 Hz, J2,1 = 1.2 Hz, 1 H, H-2man), 5.43 (pseudo-t,
3
3Japp,4,3/5 = 10.0 Hz, 1 H, H-4man), 5.22 (dd, J3,4 = 10.1 Hz,
MS (ESI): m/z (%) = 912.3 ([M + H]+, 47), 934.4 ([M + Na]+, 100).
ESI-HRMS: m/z calcd for [C54H57NO12 + Na]+: 934.3778; found:
3
3J3,2 = 3.5 Hz, 1 H, H-3man), 4.97 (d, 2J = 11.0 Hz, 1 H, CH2Ph), 4.85
(d, 2J = 11.0 Hz, 1 H, CH2Ph), 4.84 (d, 2J = 11.1 Hz, 1 H, CH2Ph),
934.3792.
2
2
4.80 (d, J = 11.7 Hz, 1 H, CH2Ph), 4.78 (d, J = 11.8 Hz, 1 H,
CH2Ph), 4.59 (d, 2J = 12.2 Hz, 1 H, CH2Ph), 4.55 (d, 2J = 12.5 Hz,
1 H, CH2Ph), 4.52 (d, 2J = 11.2 Hz, 1 H, CH2Ph), 4.17 (dd,
Acknowledgment
2J6a,6b = 12.1 Hz, J6a,5 = 5.0 Hz, 1 H, H-6aman), 4.08 (dd,
3
2J6b,6a = 12.1 Hz, 3J6b,5 = 2.5 Hz, 1 H, H-6bman), 4.05 (dd, 3J2,3 = 9.5
This work was supported by the Bundesministerium für Bildung,
Forschung und Technologie (BMBF, grant no. 0315139). We thank
Dr. S. Franke (deceased) and Dr. N. Hanold for mass spectrometry,
Dr. T. Hackl and Dr. J. C. Liermann for NMR spectroscopy as well
as Dr. D. Schollmeyer for X-ray crystallography.
Hz, J2,1 = 5.6 Hz, 1 H, H-2glc), 3.97 (dd, J3,2 = 9.5 Hz, J3,4 = 7.8
Hz, 1 H, H-3glc), 3.68 (dt, 3J5,4 = 9.8 Hz, 3J5,6 = 3.1 Hz, 1 H, H-5glc),
3.65 (dd, 3J4,5 = 9.8 Hz, 3J4,3 = 7.8 Hz, 1 H, H-4glc), 3.59 (mc, 2 H H-
6a,bglc), 3.46 (ddd, 3J5,4 = 10.0 Hz, 3J5,6a = 5.0 Hz, 3J5,6b = 2.5 Hz, 1
H, H-5man).
3
3
3
13C NMR (151 MHz, CDCl3): δ = 171.0, 170.5, 170.3, 170.0
(4 × C=O), 138.3, 138.2, 137.8, 137.1 (4 × C-1Ph), 135.4 (C-7aind),
130.0 (C-2ind), 128.8 (2 C), 128.7 (2 C), 128.6 (2 C), 128.51, 128.46
(2 C), 128.44 (2 C), 128.42 (2 C), 128.2 (2 C), 128.01, 128.00,
127.8, 127.6 (2 C), (20 × CHPh), 127.3 (C-3aind), 123.2 (C-4ind),
122.1 (C-6ind), 119.6 (C-5ind), 111.0 (C-7ind), 110.7 (C-3ind), 82.0 (C-
3glc), 80.5 (C-2glc), 78.4 (C-4glc), 75.9 (C-5man), 75.4, 74.9, 73.9
(3 × CH2Ph), 73.8 (C-1man), 73.6 (CH2Ph), 73.0 (C-5glc), 72.4 (C-
3man), 71.5 (C-2man), 69.6 (C-1glc), 69.0 (C-6glc), 66.5 (C-4man), 63.1
(C-6man), 21.01, 20.95, 20.92, 20.88 (4 × COCH3).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.omnorinIftangonmSorniuifIatoprtngiSutpor
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54, 9913.
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4475.
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Angew. Chem. Int. Ed. 2004, 43, 2915.
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Lett. 2010, 12, 3934.
MS (ESI): m/z (%) = 970.6 ([M + H]+, 100), 992.5 ([M + Na]+, 87).
ESI-HRMS: m/z calcd for [C56H59NO14 + Na]+: 992.3833; found:
922.3827.
3-(2,3,4-Tri-O-acetyl-β-L-fucopyranosyl)-2-(2,3,4,6-tetra-O-
benzyl-α-D-glucopyranosyl)-1H-indole (44)
The title compound was prepared according to the general proce-
dure from 2-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-1H-in-
dole (39; 84 mg, 0.13 mmol), 2,3,4-tri-O-acetyl-α-L-fucopyranosyl
trichloroacetimidate (15; 85 mg, 0.20 mmol), molecular sieves (1.5
g, 4 Å), and BF3OEt2 (20 μL, 160 μmol) in CH2Cl2 (4 mL). The re-
action mixture was cooled to –18 °C and allowed to warm to 0 °C
within 1 h. As TLC indicated little conversion, the reaction mixture
was cooled to –20 °C and more BF3OEt2 (2 μL, 160 μmol) was add-
ed. This procedure was repeated once more. Then the reaction mix-
ture was allowed to warm to –2 °C within another 1.5 h. The residue
was purified by flash chromatography (eluent: cyclohexane–
EtOAc, 3.5:1) to afford 44 (64 mg, 54%); colourless oil; Rf = 0.36
(cyclohexane–EtOAc, 2:1); [α]D22 +34.4 (c = 1.00, CH2Cl2).
1H NMR, COSY, ROESY, HSQC, HMBC (600 MHz, CDCl3):
δ = 9.41 (s, 1 H, NH), 7.88 (d, 3J4,3 = 5.8 Hz, 1 H, H-4Ind), 7.12–7.40
(m, 23 H, 20 × HPh, H-5ind, H-6ind, H-7ind), 6.00 (br s, 1 H, H-2fuc),
5.61 (d, 3J1,2 = 3.5 Hz, 1 H, H-1glc), 5.37 (d, 3J4,3 = 3.1 Hz, 1 H, H-
4fuc), 5.18 (dd, 3J3,2 = 10.1 Hz, 3J3,4 = 3.1 Hz, 1 H, H-3fuc), 5.09 (d,
3J1,2 = 9.9 Hz, 1 H, H-1fuc), 4.86 (d, 2J = 11.1 Hz, 1 H, CH2Ph), 4.80
(d, 2J = 11.2 Hz, 1 H, CH2Ph), 4.75 (d, 2J = 11.1 Hz, 1 H, CH2Ph),
(16) Bililign, T.; Griffith, B. R.; Thorson, J. S. Nat. Prod. Rep.
2005, 22, 742.
(17) Schmidt, R. R.; Hoffmann, M. Tetrahedron Lett. 1982, 23,
409.
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1996, 1623.
(19) Weck, S.; Opatz, T. Synthesis 2010, 2393.
(20) Armitt, D. J.; Banwell, M. G.; Freeman, C.; Parish, C. R.
J. Chem. Soc., Perkin Trans. 1 2002, 1743.
(21) Mukherjee, D.; Sarkar, S. K.; Chowdhury, U. S.; Taneja, S.
C. Tetrahedron Lett. 2007, 48, 663.
(22) Melnik, S. Y.; Bakhmedova, A. A.; Garaeva, L. D.;
Goryunova, O. V.; Miniker, T. D.; Plikhtyak, I. L.; Ektova,
L. V.; Ivanova, T. P.; Yartseva, I. V. Bioorg. Khim. 1996, 22,
458; Chem. Abstr. 1996, 125, 301361k.
2
2
4.72 (d, J = 11.4 Hz, 1 H, CH2Ph), 4.68 (d, J = 11.9 Hz, 1 H,
CH2Ph), 4.62 (d, 2J = 11.1 Hz, 1 H, CH2Ph), 4.54 (d, 2J = 12.4 Hz,
1 H, CH2Ph), 4.52 (d, 2J = 12.4 Hz, 1 H, CH2Ph), 4.03–4.08 (m, 1
H, H-2glc), 3.93–4.00 (m, 3 H, H-3glc, H-4glc, H-5glc), 3.90 (q,
2
3
3J5,6 = 6.5 Hz, 1 H, H-5fuc), 3.84 (dd, J6a,6b = 10.2 Hz, J6a,5 = 1.8
Hz, 1 H, H-6aglc), 3.76 (dd, 2J6b,6a = 10.2 Hz, 3J6b,5 = 2.7 Hz, 1 H, H-
6bglc), 2.26 (s, 3 H), 2.04 (s, 3 H), 1.64 (s, 3 H, 3 × COCH3), 1.20 (d,
3J6,5 = 6.5 Hz, 3 H, H-6fuc).
13C NMR, HSQC, HMBC (151 MHz, CDCl3): δ = 171.1, 170.5,
169.1 (3 × C=O), 138.2, 138.1, 138.0, 137.2 (3 × C-1Ph), 135.8 (C-
7aind), 133.8 (C-2ind), 128.8 (2 C), 128.6 (2 C), 128.50 (4 C), 128.46
(23) Messaoudi, S.; Sancelme, M.; Polard-Housset, V.; Aboab,
B.; Moreau, P.; Prudhomme, M. Eur. J. Med. Chem. 2004,
39, 453.
Synthesis 2012, 44, 1385–1397
© Georg Thieme Verlag Stuttgart · New York

PAPER
Diglycosylated Indoles
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(41) Full details have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
no. CCDC-863302. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or
from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax:
+44(1223)336033; E-mail: deposit@ccdc.cam.asc.uk.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1385–1397