Synthesis of substituted mono- and diindole C-nucleoside analogues from sugar terminal alkynes by sequential sonogashira/heteroannulation reaction

Article abstract of DOI:10.1021/jo501488x

The synthesis of substituted mono- and diindole C-nucleoside analogues has been achieved in good to excellent yields by sequential Sonogashira coupling/NaAuCl₄-catalyzed heteroannulation reactions of substituted 2-iodoanilines with various sugar terminal alkynes in one pot. The method is general, mild, and efficient and suitable for a wide range of sugar substrates, and 42 examples are given. The amino group of the substituted 2-iodoanilines is unprotected. The sugar terminal alkynes include furanosides, pyranosides, and acyclic glycosides with free hydroxyl groups, sensitive functional subtituents, and various protecting groups having different steric hindrance. (Chemical Equation Presented).

Full text of DOI:10.1021/jo501488x

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Article
Synthesis of substituted momo- and di-indole C-nucleoside analogs from
terminal sugar alkynes by sequential Sonogashira/heteroannulation reaction
Fuyi Zhang, Delong Mu, Liming Wang, Pengfei Du, Fen Han, and Yufen Zhao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo501488x • Publication Date (Web): 22 Sep 2014
Downloaded from http://pubs.acs.org on September 28, 2014
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Synthesis of substituted momoꢀ and diꢀindole Cꢀnucleoside analogs from terminal
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sugar alkynes by sequential Sonogashira/ heteroannulation reaction
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Fuyi Zhang,*,† Delong Mu,† Liming Wang,† Pengfei Du,† Fen Han,† and Yufen Zhao†,‡
†The College of Chemistry and Molecular Engineering, The Key Laboratory of Chemical
Biology and Organic Chemistry of Henan Province, Zhengzhou University, Zhengzhou,
450001, China
‡College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical
Biology of Fujian Province, Xiamen University, Xiamen, 361005, China
*Eꢀmail: zhangfy@zzu.edu.cn
R
Pd(PPh3)2Cl2, CuI,
Et3N, rt, then:
N
H
Sugar
I
R
Sugar
R
R
+
NaAuCl4 2H2O,
NH2
THF, 30 ꢀ 55 0C
Sugar
1a ꢀ 1i
NH
42 examples
73 ꢀ 90% yields
N
H
Sugar
R = H, CH3, F, Cl, Br
3aa ꢀ 3ig
ABSTRACT: The synthesis of substituted monoꢀ and diꢀindole Cꢀnucleoside analogs has
been achieved in good to excellent yields by sequential Sonogashira coupling/NaAuCl4
catalyzed heteroannulation reactions of substituted 2ꢀiodoanilines with various sugar
terminal alkynes in one pot. The method is general, mild and efficient and suitable for a
wide range of sugar substrates, and forty two examples are given. The amino group of the
substituted 2ꢀiodoanilines is unprotected. The sugar terminal alkynes include furanosides,
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pyranosides and acyclic glycosides with free hydroxyl groups, sensitive functional
subtituents and various protected groups having different steric hindrance.
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INTRODUCTION
Heteroaryl Cꢀnucleosides have received much attention due to their interesting biological
activities and their use in the extension of the genetic alphabet.1 Indole represents an
important artificial DNA base because of its structural similarity with guanine and
adenine.1g,2 It is also a very crucial charge transport trap in DNA, especially for Cꢀ2 or
Cꢀ3 substituted indole Cꢀnucleosides.3 Figure 1 shows αꢀCꢀmannosyltryptophan
discovered in Trp7 of ribonuclease 24 and two Cꢀ2 substituted indole Cꢀnucleoside
analogs isolated recently from the roots of Isatis indigotica, which display significant
cytotoxic activities against human liver cancer HepG2 cells, human myeloid leukemia
HLꢀ60 and human myeloid leukemia Mata.5 The methods for the synthesis of Cꢀ2 and
Cꢀ3 substituted indole derivatives are well documented.6 Catalytic heteroannulation of
functionalized 2ꢀalkynylaniline derivatives is the most efficient approach for the
synthesis of Cꢀ2 substituted indole derivatives.6aꢀ6j,7 Many kinds of catalysts were
reported for these cyclizations, and transitionꢀmetalꢀpromoted heteroannulations have
been achieved.6g−6j,8 Baseꢀpromoted heteroannulations of 2ꢀalkynylphenylamines and
their Nꢀprotected derivatives have also been established.6i,6k,9 I2 and iodinating reagent
were successfully used for electrophilic cyclizations to synthesize Cꢀ2 substituted
3ꢀiodoindoles.10
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O
NH
H
HO
OH
O
6
7
αꢀCꢀmannosyl tryptophan
N
OH
H
8
9
OH
HO
NC
HO
NC
H3CO
OH
OH
OH
OH
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O
N
O
NH
HO
HO
OCH3
Cytotoxic activity against HL60 cells (IC50
5.1 mM) and human myeloid
leukemia Mata cells (IC50 = 12.1 mM)
Cytotoxic activity against human liver cancer
HepG2 cells (IC50 2.1 mM) and human
myeloid leukemia HL60 cells (IC50 = 1.3 mM).
=
=
Figure 1. Examples of naturally occurring indole Cꢀnucleoside analogs.
Among the approaches used for the synthesis of Cꢀ2 and Cꢀ3 substituted indole
Cꢀnucleoside analogs, the most common method is the addition of Nꢀprotected
lithioꢀindoles onto sugar lactones or lactols followed by reduction.11 Cꢀglycosylation of
indole derivatives with glycosyl donors promoted by boron trifluoride–diethyl etherate12
or trifluoromethanesulfonic anhydride13 has also been employed. Recently, catalytic
heteroannulation of sugar 2ꢀalkynylanilines has been developed. Minehan and coꢀworkers
reported a concise route to a natural indole Cꢀnucleoside analog5 by Sonogashira
coupling of sugar alkyne with 2ꢀiodoꢀ3ꢀnitrophenol, nitro group reduction, and
subsequent heteroannulation of sugar 2ꢀalkynylaniline promoted by potassium
tertꢀbutoxide.14 Hocek’s group synthesized 1ꢀαꢀ and 1ꢀβꢀ(indolꢀ2ꢀyl)ꢀ2´ꢀdeoxyribose
Cꢀnucleosides based on the Sonogashira reaction of 1αꢀ and 1βꢀethynyldeoxyribose and
2ꢀhaloanilines followed by a Pdꢀcomplex catalyzed cyclization.15 Isobe reported the
synthesis of Cꢀ2 substituted indole Cꢀnucleoside analogs by a Pdꢀmediated Sonogashira
coupling of sugar alkynes with Nꢀtosylꢀ2ꢀiodoaniline, a Cuꢀmediated Castro cyclization,
and subsequent removal of Nꢀtosyl group by tetrabutylammonium fluoride.16 In view of
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the biological importance of Cꢀ2 substituted indole Cꢀnucleoside analogs, and our interest
in the syntheses of biologically active carbohydrate analogues17 as well as Cꢀsubstituted
sugar analogues,18 we describe herein a general, mild and efficient synthesis of Cꢀ2
substituted monoꢀ and diꢀindole Cꢀnucleoside analogs from various sugar alkynes.
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RESULTS AND DISCUSSION
Terminal alkynes serving as building blocks for the synthesis of substituted indoles by
Sonogashira coupling with substituted 2ꢀhaloanilines have been reported and most
substrates were phenylacetylene.6e−6o In order to find a general reaction system tolerant of
various functional groups and structural diversity of sugar alkynes in one pot, at the
outset, 1a19 (Scheme 1) with sterically bulky triisopropylsilyl, unprotected hydroxyl
groups and sensitive trimethylsilylethynyl group was deliberately used as a model to
perform the Sonogashira coupling/heteroannulation reaction. In the optimization studies,
the twoꢀstep reactions were examined, respectively. Sonogashira coupling reaction of 1a
with 2ꢀiodoaniline was performed under classical conditions in the presence of
Pd(PPh3)2Cl2, CuI and Et3N in degassed solvent. The influence of solvent, the amount of
the catalyst and temperature on the reaction was examined in detail. When the reaction
was carried out in THF, the coupling product sugar substituted 2ꢀethynylaniline 2aa
(Scheme 1) was obtained in 85% yield. The change of a solvent to MeCN and CH2Cl2
gave rise to 2aa in 80% and 88% yield, respectively. In these cases, the undesired
homocoupling product 1,3ꢀdiyne was not observed. The best result was obtained using
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1.1 equiv of 2ꢀiodoaniline, 1.0 equiv of 1a, 3 mol% of Pd(PPh3)2Cl2 and 5 mol% of CuI
in pure degassed Et3N. The coupling reaction was complete within 5 h at rt and 2aa was
attained in 95% isolated yield. Heteroannulation product 3aa was not obtained under
these conditions. After the coupling reaction of 1a with 2ꢀiodoaniline was accomplished,
an attempt to carry out a tandem reaction by increasing the temperature to 60 0C gave 3aa
only in 18% yield.
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Scheme 1. Synthesis of 2aa and 3aa
OH
O
OH
O
2ꢀIodoaniline (1.1 eq),
Pd(PPh3)2Cl2 (3 mol%),
CuI (5 mol%), Et3N, rt,
OH
O
SiMe3
SiMe3
SiMe3
Conditions
HO
NH2
HO
HO
OTIPS
NH
OTIPS
OTIPS
0.7 mmol
3aa
2aa
1a
The second task was the development of the high yielding heteroannulation of 2aa
(Table 1). Although many examples for the intramolecular heteroannulation of
2ꢀalkynylaniline to indole were reported,6aꢀ6j,7 elevated temperature, prolonged reaction
time in strong basic or Lewis acidic media are not suitable for the sugar substituted
alkynylaniline possessing complex structures and sensitive functional substituents. In
order to get a general and efficient catalytic system for heteroannulation of various sugar
2ꢀethynylanilines, many catalysts were scanned using isolated 2aa as starting material
and some results are listed in Table 1. Strong bases such as tꢀBuOK in THF and NaNH2
0
in DMF at 50 C gave 3aa in very low yields of 12% and 15% (entries 1 and 2). In the
two cases, TLC indicated most of 2aa decomposed. The change of catalyst to a Lewis
0
acid gave better results. The use of ZnCl2 in toluene at 80 C afforded 3aa in 20% yield,
and InBr3 gave the similar result (entries 3 and 4). A slight increase in yield of 28% was
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obtained in toluene by the use of Cu(OTf)2 (entry 5). When Pd(MeCN)2Cl2 was used in
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8
0
MeCN at 60 C, 3aa was obtained in 38%, which was better than that using PdCl2
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(entries 7 and 8). Fortunately, NaAuCl4·2H2O was found to be an efficient catalyst for
heteroannulation of 2aa to indole Cꢀnucleoside. In the presence of 3 mol % of
NaAuCl4·2H2O, the best yield of 3aa (86%) was achieved in THF at 50 0C (entry 9).
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Table 1. Heteroannulation of Sugar 2ꢀEthynylaniline 2aa under
Various Conditionsa
OH
OH
O
SiMe3
O
SiMe3
HO
HO
NH2
NH
OTIPS
OTIPS
3aa
2aa
Entry
1
Catalyst
t-BuOK
NaNH2
ZnCl2
Solvent
THF
T
(0C)
Time (h)
Yield (%)b
50
50
80
80
80
80
60
60
50
50
6
12
15
20
22
28
20
38
30
86
70
2
DMF
5
3
Toluene
Toluene
Toluene
(CH2Cl)2
MeCN
DMF
4.5
3
4
InBr3
5
Cu(OTf)2
CuCl2
3
6
3.5
5
7
Pd(MeCN)2Cl2
PdCl2
8
5.5
4.5
5
9
NaAuCl4—2H2Oc
NaAuCl4—2H2O
THF
10
EtOH
aConditions: 0.4 mmol sugar 2-ethynylaniline 2aa, 5 mol % catalyst, 6 mL
solvent. bIsolated yield. c3 mol %.
After obtaining the optimal conditions for the two steps, we carried out Sonogashira
coupling/heteroannulation reaction in one pot. When the coupling of 1a with
2ꢀiodoaniline was finished under the optimal conditions, Et3N was removed; THF and 3
0
mol % of NaAuCl4·2H2O were then added and the mixture stirred for 4.5 h at 50 C to
afford 3aa in 83% yield. In order to examine the electronic effect of the substituents of
2ꢀiodoaniline on the reactions and to obtain different substituted indole patterns for
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nucleobase surrogate, 2ꢀiodoanilines with electronꢀdonating, electronꢀneutral, and
electronꢀwithdrawing substituents were used to react with 1a. Fortunately, all cases the
sequence proceeded smoothly to give the corresponding products in high yields (Table 2,
entry 1). Next, terminal sugar diyne 1b (entry 2) having a sterically bulky
triisopropylsilyl group and two unprotected hydroxyl groups was used to react with some
substituted 2ꢀiodoaniline to test this protocol. The corresponding diꢀindole Cꢀnucleoside
analogs with electronꢀneutral, electronꢀdonating and electronꢀwithdrawing substituents in
the indole rings were afforded in high yields.
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To investigate the scope and generality of this method further, different other sugar
alkynes including sugars in furanose, pyranose and acyclic forms with various protected
groups and free hydroxyl groups having different steric hindrance were employed in
reactions with various substituted 2ꢀiodoanilines. The results are also summarized in
Table 2. The substituted 2ꢀiodoaniline having electronꢀdonating substituent gave a
slightly higher yield than that having an electronꢀneutral or electronꢀwithdrawing
substituent. This is the same as the cases for 1a and 1b described. The steric hindrance of
the sugar alkynes also affects the Sonogashira coupling/heteroannulation reaction. For the
furanoside alkynes 1c−1e (Table 2, entries 3−5), 1c with trans isopropylidene next to
ethynyl exhibited clean reaction and afforded Cꢀnucleoside analogs 3ca−3ce in excellent
yields (83−90%). Alkynes 1d and 1e (entries 4 and 5) with cis isopropylidene and
benzyloxy next to ethynyl respectively gave the corresponding products in slightly lower
yields (73−78%), probably due to increased steric hindrance. In these two cases, the
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starting material can’t be converted completely. Increasing the temperature and prolonged
reaction time caused the decomposition of the starting material. However, the pyranoside
alkynes 1f and 1g (entries 6 and 7) with cis and trans isopropylidenes next to ethynyl
respectively, proceeded very smoothly and the corresponding products were obtained in
80−88% yields. Then we turned our attention to acyclic alkynes. Alkynes 1h and 1i
(entries 8 and 9) were used to perform the Sonogashira coupling/heteroannulation
reactions. Both acyclic alkynes are much more reactive than the furanoside and
pyranoside ones, probably because the acyclic chains are more flexible and have less
steric hindrance, leading to the corresponding substituted indole acyclic Cꢀnucleoside
analogs in excellent yields. The structures of all the new compounds (3aa−3ig) were
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1
characterized by H NMR, 13C NMR, DEPTꢀ135, 19F NMR, 2D NMR, HRMS and IR
spectra.
Table 2. Synthesis of monoꢀ and diꢀindole Cꢀnucleoside analogs
via sequential Sonogashira coupling/heteroannulation reactions
of various terminal sugar alkynes with substituted 2ꢀiodoanilines
2ꢀIodoaniline (1.1 eq),
R
Pd(PPh3)2Cl2 (3 mol%),
N
Sugar
Sugar
I
CuI (5 mol%), Et3N, rt,
H
R
R
+
then: NaAuCl4 2H2O
(3.0 mol%), THF,
30 ꢀ 60 0C
R
NH2
Sugar
1a ꢀ 1i
NH
N
H
R = H, CH3, F, Cl, Br
Sugar
3aa ꢀ 3ig
Entry
Terminal sugar alkynes
OH
Product, Temperature, Time, Yielda
OH
O
SiMe3
R
HO
O
SiMe3
NH
OTIPS
HO
1
3aa: R = H, 50 0C, 5.0 h, 83%
3ab: R = CH3,50 0C, 4.0 h, 87%
3ac: R = F, 50 0C, 10.0 h, 78%
3ad: R = Cl, 50 0C, 8.0 h, 80%
3ae, R = Br, 50 0C, 7.5 h, 85%
OTIPS
1a
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OH
O
R
OH
O
R
HO
NH
N
OTIPS
H
2
3ba: R = H, 50 0C, 5.0 h, 88%
3bb: R = CH3,50 0C, 4.0 h, 90%
3bc: R = F, 50 0C, 8.0 h, 84%
3bd: R = Cl, 50 0C, 7.5 h, 87%
3be, R = Br, 50 0C, 6 h, 85%
HO
OTIPS
1b
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R
OCH3
N
O
OCH3
H
O
O
O
3
O
O
3ca: R = Cl, 50 0C, 8.0 h, 83%
3cb: R = H, 50 0C, 4.0 h, 85%
3cc: R = CH3, 50 0C, 3.0 h, 90%
3cd: R= F, 50 0C, 10.0 h, 80%
3ce: R= Br, 50 0C, 7.5 h, 83%
1c
R
O
O
O
O
O
N
O
H
4
3da: R = F, 55 0C, 18.0 h, 73%
3db: R = H, 45 0C , 24.0 h, 75%
3dc: R = CH3, 50 0C, 24.0 h, 78%
1d
OCH3
OCH3
R
OBn
OBn
O
N
O
H
5
O
O
1e
O
O
3ea: R = F, 50 0C, 24.0 h, 73%
3eb: R = H, 40 0C , 10.0 h, 77%
R
HN
O
O
O
O
O
O
6
O
O
O
O
1f
3fa: R = H, 45 0C, 8.0 h, 82%
3fb: R = CH3, 45 0C , 5.0 h, 85%
3fc: R = F, 55 0C, 9.0 h, 80%
3fd: R = Cl, 55 0C, 8.0 h, 84%
3fe: R = Br, 50 0C, 7.5 h, 87%
O
CMe2
O
O
O
CMe2
R
O
NH
O
O
3ga: R = H, 55 0C, 6.5 h, 82%
3gb: R = CH3, 45 0C , 5.0 h, 88%
3gc: R = F, 55 0C, 9.0 h, 80%
3gd: R = Cl, 55 0C, 8.0 h, 85%
3ge: R = Br, 55 0C, 7.5 h, 85%
7
O
CMe2
O
1g
O
CMe2
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O
OH
6
7
8
9
TrO
O
OH
R
8
NH
TrO
O
3ha: R = H, 30 0C, 3.0 h, 87%
3hb: R = CH3, 45 0C , 5.0 h, 90%
3hc: R = F, 45 0C, 4.0 h, 83%
3hd: R = Cl, 35 0C, 4.0 h, 89%
3he: R = Br, 30 0C, 5.0 h, 87%
1h
O
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R1
R2
OH
H
O
NH
OH
H
O
O
O
O
9
O
3ia: R1 = R2 = H, 30 0C, 4.0 h, 88%
3ib: R1 = CH3, R2 = H, 25 0C, 3.0 h, 90%
3ic: R1 = F, R2 = H, 45 0C, 5.0 h, 86%
3id: R1 = H, R2 = F, 55 0C, 3.5 h, 84%
3ie: R1 = Cl, R2 = H, 35 0C, 5.0 h, 85%
3if: R1 = H, R2 = Cl, 50 0C, 4.0 h, 90%
3ig: R1 = Br, R2 = H, 30 0C, 5.0 h, 88%
O
O
1i
aIsolated yield
CONCLUSIONS
We have developed a new approach to synthesize substituted monoꢀ and diꢀindole
Cꢀnucleoside analogs by the sequential Sonogashira coupling/heteroannulation reactions
of substituted 2ꢀiodoanilines with terminal sugar alkynes. Various substituted indoles as
the isosterical surragates of the structurally similar guanine and adenine have been
coupled in the sugars. This method is simple, mild and efficient and the desired products
were obtained in good to excellent yields. The scope and generality have been examined
and forty two examples are given. The sugar alkynes include furanosides, pyranosides,
and acyclic glycosides derived from various cheap and abundant natural sugars. The
reaction conditions are tolerant of various structurally complex sugars having sterically
bulky groups, unprotected hydroxyl groups, sensitive substituents, as well as various
protecting groups. The modification and biological study of these Cꢀnucleoside analogs
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EXPERIMENTAL SECTION
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Synthesis of 3,7ꢀAnhydroꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ6ꢀCꢀethynylꢀ4ꢀOꢀ
(triisopropylsily1)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (1a).19 A solution of
AgNO2 (10.7 g, 69.5 mmol) in MeOH/H2O 25:8 (33 mL) was added to a solution of
protected 1,4ꢀdideoxyꢀ1,4ꢀdiethyny1ꢀβꢀDꢀglucopyranose19 (11.6 g, 23.3 mmol) in MeOH
0
(120 mL). The mixture was stirred at rt for 4 h. Then it was cooled to 0 C, treated with
saturated KCN solution (18 mL), carefully neutralized with 2 N HCl (ca. 35 mL) and
evaporated to remove MeOH. The residue was dissolved in EtOAc (80 mL), washed with
water (2 × 15 mL). The organic phase was dried over Na2SO4 and evaporated to dryness
to give 1a (8.9 g, 90%) as a white solid. Rf = 0.5 (silica gel F254, 3:1, petroleum
ether/EtOAc); Mp: 136−138 0C; 1H NMR (400 MHz, CDCl3) δ 3.97 (d, 1H, J = 9.2 Hz),
3.94−3.93 (m, 1H), 3.77−3.71 (m, 1H), 3.63 (t, 1H, J = 8.4 Hz), 3.57−3.51 (m, 1H),
3.48−3.44 (m, 1H), 2.58−2.52 (m, 1H), 2.47 (s, 1H), 2.22 (d, 1H, J = 2.4 Hz), 2.08 (s,
1H), 1.30−1.10 (m, 21H), 0.17 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 102.3, 91.4, 80.2,
79.0, 77.0, 75.3, 73.0, 72.1, 63.6, 37.6, 18.5, 13.2, 0.3.
Synthesis of 3,7ꢀAnhydroꢀl,1,2,2ꢀtetradehydroꢀl,2,6ꢀtrideoxyꢀ6ꢀCꢀethynylꢀ4ꢀOꢀ
(triisopropylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (1b).19 A 0.5 N NaOH solution (3 mL) was
added to a solution of protected 1,4ꢀdideoxyꢀ1,4ꢀdiethyny1ꢀβꢀDꢀglucopyranose19 (1.0 g,
2.0 mmol) in MeOH (30 mL). The mixture was stirred at rt until TLC indicated the
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completion of the reaction. Then it was neutralized with 1 N HCl (1.5 mL) and
evaporated to remove MeOH. The residue was dissolved in EtOAc (30 mL), washed with
water (2 × 5 mL). The organic phase was dried over Na2SO4 and evaporated to dryness to
give 1b (0.64 g, 90%) as a white solid. Rf = 0.5 (silica gel F254, 3:1, petroleum
ether/EtOAc); Mp: 113−115 0C; 1H NMR (400 MHz, CDCl3) δ 3.97 (dd, 1H, J = 9.2 Hz,
J = 2.2 Hz), 3.94−3.91 (m, 1H), 3.82−3.71 (m, 1H), 3.66 (t, 1H, J = 9.0 Hz), 3.58−3.53
(m, 1H), 3.50−3.46 (m, 1H), 2.60−2.54 (m, 1H), 2.50 (s, 1H), 2.49 (d, 1H, J = 2.1 Hz),
2.23 (d, 1H, J = 2.4 Hz), 2.09 (s, 1H), 1.26−1.09 (m, 21H); 13C NMR (100 MHz, CDCl3)
δ 81.1, 80.2, 79.0, 76.7, 75.1, 74.8, 73.1, 71.3, 63.4, 37.7, 18.4, 13.0.
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General procedure for the preparation of 1c−1g. 20
A solution of CBr4 (2 equiv) in dry CH2Cl2 was added to a mixture of zinc (3 equiv),
0
PPh3 (3 equiv) and dry CH2Cl2 at 0 C. Then sugar aldehyde20c−20i (1.0 equiv) in dry
CH2Cl2 was added dropwise for 10 min. The mixture was stirred at rt until TLC indicated
the complete conversion of sugar aldehyde. Then it was evaporated and the residue was
purified by column chromatography (silica gel, 6:1−3:1, petroleum ether/EtOAc) to give
a syrup.
A 2.5 M nꢀbutyllithium solution in dry THF (2.5 equiv) was added to a solution of the
0
syrup (1.0 equiv) in dry THF at −45 C. The mixture was stirred until TLC indicated the
completion of the reaction. It was quenched by water (ca. 2.5 equiv) and evaporated. The
residue was dissolved in EtOAc, washed with water. The organic phase was dried over
Na2SO4 and evaporated. The residue was purified by column chromatography (silica gel,
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5:1−3:1, petroleum ether/EtOAc) to give 1c−1g.
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1ꢀOꢀMethylꢀ5,6ꢀdideoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀriboꢀhexꢀ5ꢀynofuranoside
(1c).20c,20d White solid, 457 mg, 68% yield; Rf = 0.5 (silica gel F254, 6:1, petroleum
ether/EtOAc); Mp: 63−64 0C 1H NMR (400 MHz, CDCl3) δ 4.97 (s,1H), 4.78 (d, 1H, J3, 2
= 6.0 Hz), 4.68 (d, 1H, J = 2.8 Hz), 4.58 (d, 1H, J = 6.0 Hz), 3.27 (s, 3H), 1.34, 1.20 (2s,
each 3H); 13C NMR (100 MHz, CDCl3) δ 112.5, 109.2, 85.3, 85.1, 81.5, 74.6, 74.1, 54.1 ,
26.2, 24.8.
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1ꢀOꢀMethylꢀ5,6ꢀdideoxyꢀ2,3ꢀOꢀisopropylideneꢀαꢀDꢀlyxoꢀhexꢀ5ꢀynofuranoside
(1d).
20c,20d
Yellow solid, 486 mg, 74% yield; Rf = 0.5 (silica gel F254, 6:1, petroleum
ether/EtOAc); Mp: 45−46 0C; 1H NMR (400 MHz, CDCl3) δ 4.90 (s, 1H), 4.72 (d, 1H, J
= 4.0 Hz), 4.60 (dd, 1H, J = 5.6 Hz, J = 4.0 Hz), 4.53 (d, 1H, J = 5.6 Hz), 3.32 (s, 3H),
13
1.50, 1.32 (2s, each 3H); C NMR (100 MHz, CDCl3) δ 113.4, 107.2, 84.8, 80.6, 77.4,
76.6, 70.6, 55.0, 26.3, 25.3.
3ꢀOꢀBenzylꢀ5,6ꢀdideoxyꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxyloꢀhexꢀ5ꢀynofuranose (1e).20c−20g
Colourless oil, 438 mg, 72% yield; Rf = 0.6 (silica gel F254, 4:1, petroleum ether/EtOAc);
1H NMR (400 MHz, CDCl3) δ 7.40−7.27 (m, 5H), 5.96 (d, 1H, J = 3.6 Hz), 4.83 (t, 1H, J
= 2.4 Hz, J = 2.8 Hz), 4.81 (d, 1H, J = 12.4 Hz), 4.74 (d, 1H, J = 12.4 Hz), 4.58 (d, 1H, J
= 3.6 Hz), 4.02 (d, 1H, J = 2.8 Hz), 2.64 (d, 1H, J = 2.4 Hz), 1.49, 1.31 (2s, each 3H); 13C
NMR (100 MHz, CDCl3) δ 137.4, 128.5, 128.0, 127.8, 112.0, 104.7, 82.8, 82.4, 77.6,
76.6, 72.6, 70.7, 26.8, 26.2.
6,7ꢀDideoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀαꢀDꢀgalactoꢀheptꢀ6ꢀynopyranose
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(1f).20c,20d,20g Colourless oil, 583 mg, 76% yield; Rf = 0.7 (silica gel F254, 4:1, petroleum
ether/EtOAc); 1H NMR (400 MHz, CDCl3) δ 5.51 (d, 1H, J = 4.8 Hz), 4.60−4.58 (m, 2H),
4.29−4.25 (m, 2H), 2.51 (d, 1H, J = 2.0 Hz), 1.48, 1.47, 1.32, 1.27 (4s, each 3H); 13C
NMR (100 MHz, CDCl3) δ 109.9, 108.9, 96.4, 78.8, 74.5, 72.6, 70.6, 70.1, 60.0, 26.1,
25.9, 24.7, 24.3.
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1,2ꢀDideoxyꢀ3,4:5,6ꢀdiꢀOꢀisopropylideneꢀβꢀDꢀarabinoꢀheptꢀ1ꢀynꢀ3ꢀuloꢀ3,7ꢀpyranose
(1g).20h,20i Colourless oil, 532 mg, 80% yield; Rf = 0.7 (silica gel F254, 4:1, petroleum
1
ether/EtOAc); H NMR (400 MHz, CDCl3) δ 4.53 (dd, 1H, J = 2.0 Hz, J = 8.0 Hz), 4.43
(d, 1H, J = 2.0 Hz), 4.18−4.15 (m, 1H), 3.73−3.67 (m, 2H), 2.58 (s, 1H), 1.46, 1.45, 1.40,
13
1.29 (4s, each 3H); C NMR (100 MHz, CDCl3) δ 109.6, 109.5, 95.8, 81.8, 75.7, 72.4,
70.4, 70.2, 61.2, 26.1, 26.0, 24.6, 24.2.
General procedure for the preparation of 1h and 1i.21,22 A mixture of sugar
hemiacetal (10.0 mmol), anhydrous K2CO3 (4.1 g, 30.0 mmol) and dry MeOH (20 mL)
was refluxed, to which Ohira's reagent (6.7 g, 35.0 mmol) in dry MeOH (20 mL) was
added dropwise for 6−8 h. TLC indicated completion of the reaction. The mixture was
evaporated to dryness and water (30 ml) was added. The solution was extracted with
EtOAc (4 × 10 mL). The combined organic phases were dried over Na2SO4 and
evaporated. The residue was purified by column chromatography (silica gel, 6:1−4:1,
petroleum ether/EtOAc ) to give 1g or 1i.
3,4ꢀIsopropylideneꢀ6ꢀOꢀtriphenylmethylꢀ1,2ꢀdideoxyꢀDꢀriboꢀhexꢀ1ꢀynitol
(1h).22,23
Colourless oil, 3.6 g, 85% yield; Rf = 0.6 (silica gel F254, 4:1, petroleum ether/EtOAc); 1H
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NMR (400MHz, CDCl3) δ 7.50−7.28 (m, 15H), 4.73−4.71 (dd, J = 6.4 Hz, 1H),
4.25−4.22 (t, J = 6.0 Hz, 1H), 3.91 (s, 1H), 3.35−3.34 (d, J = 5.2 Hz, 2H), 2.53 (d, J = 3.6
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9
13
Hz, 1H), 2.49 (d, J = 2.0 Hz), 1.52 (s, 3H), 1.40 (s, 3H); C NMR (100 MHz, CDCl3) δ
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143.7, 128.7, 127.9, 127.2, 110.8, 99.8, 87.1, 82.0, 74.4, 70.9, 66.9, 64.4, 26.9, 26.1.
3,4:6,7ꢀDiꢀOꢀisopropylideneꢀ1,2ꢀdideoxyꢀDꢀmannoꢀhexꢀ1ꢀynitol (1i).22−24 Colourless
oil, 2.2 g, 86% yield; Rf = 0.7 (silica gel F254, 5:1, petroleum ether/EtOAc); 1H NMR (400
Hz, CDCl3) δ 4.68 (dd, 1H, J = 1.4 Hz, J = 7.6Hz), 4.30 (dd, 1H, J = 7.6 Hz, J= 1.6 Hz),
4.02−4.14 (m, 3H), 3.58 (br s, 1H), 2.56 (d, 1H, J = 1.4 Hz), 2.23 (d, 1H, J = 7.6Hz), 1.53,
1.45, 1.44, 1.38 (s, each 3H); 13C NMR (100 MHz, CDCl3) δ 110.1, 109.5, 80.8, 80.6,
76.2, 74.9, 69.8, 66.8, 66.6, 26.8, 26.6, 26.2, 25.3.
Synthesis
of
3,7ꢀAnhydroꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ6ꢀCꢀ[(2ꢀ
aminophenyl)ethynyl]ꢀ4ꢀOꢀ(triisopropylsily1)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀ
guloꢀoctitol (2aa). A mixture of 2ꢀiodoaniline (90 mg, 0.77 mmol), Pd(PPh3)2Cl2 (15 mg,
0.021 mmol), CuI (7 mg, 0.035 mmol), and Et3N (3 mL) was degassed. Then sugar
alkyne 1a (297 mg, 0.70 mmol) in Et3N (3 mL) was injected with syringe. The mixture
was stirred at room temperature until TLC indicated completion of the reaction. It was
evaporated to remove Et3N. The residue was purified by column chromatography (silica
gel, 3:1, petroleum ether/EtOAc) to give 2aa (342 mg, 95%) as a brown oil: Rf = 0.5
(silica gel F254, 3:1, petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.22 (dd, 1H,
J = 1.1 Hz, J = 7.6 Hz, H−6'), 7.11−7.07 (m, 1H, H−5'), 6.68 (d, 1H, J = 7.9 Hz, H−4'),
6.65 (d, 1H, J = 7.4 Hz, H−7'), 3.99 (d, 1H, J = 9.3 Hz, H−3), 3.97 (d, 1H, J = 2.4 Hz,
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H−8a), 3.78 (dd, 1H, J = 5.8 Hz, J = 11.7 Hz, H−8b), 3.68 (t, J = 8.5 Hz, J = 10.2 Hz,
H−5), 3.54−3.49 (m, 1H, H−7), 2.78 (t, 1H, J = 10.3 Hz, H−6), 1.29−1.10 (m, 21H,
Si(CH(CH3)2)3), 0.18 (s, 9H, Si(CH3)3); 13C NMR (100 MHz, CDCl3) δ 148.04 (C−8'),
132.21 (C−6'), 129.79 (C−5'), 118.14 (C−4'), 114.67 (C−7'), 107.64 (C−3'), 102.61 (C−2),
90.66 (C−1), 91.23 (C−1'), 81.59 (C−2'), 79.30 (C−7), 77.20 (C−5), 75.36 (C−4), 72.12
(C−3), 63.77 (C−8), 38.84 (C−6), 18.47 (Si(CH(CH3)2)3), 13.17 (Si(CH(CH3)2)3), −0.28
(Si(CH3)3) ppm; HRMS (ESI) calcd. for C28H46NO4Si2 [M+H]+ 516.2965, found:
516.2960.
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General procedure for the synthesis of 3aa−3ig. A mixture of substituted
2ꢀiodoaniline (0.77 mmol), Pd(PPh3)2Cl2 (0.021 mmol), CuI (0.035 mmol) and Et3N (3
mL) was degassed. Then sugar alkyne (0.70 mmol) in Et3N (3 mL) was injected with
syringe. The mixture was stirred at room temperature until TLC indicated the completion
of the reaction. It was evaporated to remove Et3N. THF (8 mL) and NaAuCl4·2H2O
0
(0.021 mmol) were then added, and the mixture was stirred at 25−55 C. After TLC
indicated completion of the reaction, the mixture was evaporated. The residue was
purified by column chromatography (silica gel, 3:1−1:1, petroleum ether/EtOAc) to give
the products 3aa−3ig.
3,7ꢀAnhydroꢀ6ꢀCꢀ(indolꢀ2ꢀyl)ꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ4ꢀOꢀ(triisopropylsily
l)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (3aa). Brown foam, 299 mg, 83% yield;
0
Mp: 56−57 C; Rf = 0.7 (silica gel F254, 1:1, petroleum ether/EtOAc); [α]20D = −26.30 (c
0.66, CHCl3); IR (KBr): 3421, 3133, 2963, 2865, 1664, 1622, 1455, 1290, 1253, 1141,
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1112, 1070, 1021, 883, 803 cm−1; H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H, NH), 7.56
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(d, 1H, J4', 5' = 8.0 Hz, H−4'), 7.31 (d, 1H, J7', 6' = 8.0 Hz, H−7'), 7.18−7.08 (m, 2H, H−5',
H−6'), 6.34 (s, 1H, H−3'), 4.12 (d, 1H, J3, 4 = 8.4 Hz, H−3), 3.82−3.80 (m, 2H, H−4, H−5),
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3.70 (d, 1H, J8a, 8b = 12.0 Hz, H−8a), 3.58(br d, J = 10.4 Hz, H−7), 3.37 (dd, 1H, J8b, 7
=
4.0 Hz, J8b, 8a = 12.0 Hz, H−8b), 3.06 (t, 1H, J6, 7 = J6, 5 = 10.0 Hz, H−6), 2.38 (s, 2H,
13
2OH), 1.30−1.11 (m, 21H, Si(CH(CH3)2)3), 0.21 (s, 9H, Si(CH3)3) ppm; C NMR (100
MHz, CDCl3) δ 135.8 (C−7a'), 135.0 (C−2'), 128.5 (C−3a'), 122.0 (C−6'), 120.3 (C−4'),
120.2 (C−5'), 111.0 (C−7'), 102.7 (C−2), 99.4 (C−3'), 91.3 (C−1), 80.0 (C−7), 77.4 (C−5),
75.7 (C−4), 72.2 (C−3), 63.2 (C−8), 44.4 (C−6), 18.5 (Si(CH(CH3)2)3), 13.2
(Si(CH(CH3)2)3), −0.2 (Si(CH3)3) ppm; HRMS (ESI) calcd. for C28H46NO4Si2 [M+H]+
516.2965, found: 516.2962.
3,7ꢀAnhydroꢀ6ꢀCꢀ(5ꢀmethylindolꢀ2ꢀyl)ꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ4ꢀOꢀ(triisopro
pylsilyl)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (3ab). Brown foam, 322 mg, 87%
0
yield; Mp: 92−93 C; Rf = 0.7 (silica gel F254, 1:1, petroleum ether/EtOAc); [α]20D = −30.80
(c 0.50, CHCl3); IR (KBr) 3425, 3132, 2966, 2864, 1664, 1623, 1400, 1293, 1254, 1141,
1071, 1023, 882, 778 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 7.34 (s, 1H), 7.20
(d, 1H, J = 8.4 Hz), 6.98(d, 1H, J = 8.4 Hz), 6.25 (s, 1H), 4.12 (d, 1H, J = 8.8 Hz),
3.81−3.78 (m, 2H), 3.70 (d, 1H, J = 12.0 Hz), 3.60−3.56 (m, 1H), 3.37 (br d, 1H, J = 8.4
Hz), 3.03 (t, 1H, J = 10.2 Hz), 2.43 (s, 3H), 2.33, 2.27 (2br s, each 1H), 1.28−1.11 (m, 21H),
13
0.20 (s, 9H) ppm; C NMR (100 MHz, CDCl3) δ 135.0, 134.2, 129.4, 128.8, 123.6, 120.0,
110.7, 102.8, 99.0, 91.2, 80.0, 77.4, 75.7, 72.2, 63.3, 44.5, 21.5, 18.5, 13.2, −0.2 ppm;
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HRMS (ESI) calcd. for C29H48NO4Si2 [M+H]+ 530.3122, found: 530.3125.
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3,7ꢀAnhydroꢀ6ꢀCꢀ(5ꢀfluoroindolꢀ2ꢀyl)ꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ4ꢀOꢀ(triisop
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ropylsilyl)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (3ac). Brown foam, 291 mg,
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78% yield; Mp: 63−64 C; Rf = 0.7 (silica gel F254, 1:1, petroleum ether/EtOAc); [α]20
=
D
−30.70 (c 0.52, CHCl3); IR (KBr) 3422, 3335, 3133, 2961, 2865, 1626, 1487, 1454, 1400,
1291, 1253, 1119, 1069, 1022, 849, 813 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H),
7.22−7.17 (m, 2H), 6.92−6.86 (m, 1H), 6.30 (s, 1H), 4.12 (d, 1H, J = 8.4 Hz), 3.82−3.79
(m, 2H), 3.74 (d, 1H, J = 11.4 Hz), 3.61−3.58 (m, 1H), 3.38 (dd, J = 3.6 Hz, J= 11.4 Hz),
3.08 (t, 1H, J = 10.2 Hz), 2.36 (s, 1H), 2.26 (s, 1H), 1.29−1.11 (m, 21H), 0.20 (s, 9H)
ppm; 13C NMR (100 MHz, CDCl3) δ 158.2 (d, 1JC−F = 233.0 Hz), 137.0, 132.3, 128.9 (d,
3JC−F = 10.0 Hz), 111.6 (d, 3JC−F = 10.0 Hz), 110.3 (d, 2JC−F = 26.0 Hz), 105.1 (d, 2JC−F
=
4
24.0 Hz), 102.6, 99.5 (d, JC−F = 4.0 Hz), 91.4, 80.0, 77.4, 75.8, 72.2, 63.2, 44.2, 18.5,
13.2, −0.2 ppm; 19F NMR (376 MHz, CDCl3) δ −124.4 (dt, J1 = 9.2 Hz, J2 = 4.1 Hz) ppm;
HRMS (ESI) calcd. for C28H45FNO4Si2 [M+H]+ 534.2871, found 534.2869.
3,7ꢀAnhydroꢀ6ꢀCꢀ(5ꢀchloroindolꢀ2ꢀyl)ꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ4ꢀOꢀ(triisopro
pylsilyl)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (3ad). Brown foam, 308 mg, 80%
yield; Mp: 39−40 C; Rf = 0.7 (silica gel F254, 1:1, petroleum ether/EtOAc); [α]20D = −39.00
0
(c 0.54, CHCl3); IR (KBr) 3413, 3335, 3134, 2927, 2863, 1665, 1618, 1583, 1464, 1311,
1252, 1140, 1113, 1065, 1022, 848, 805 cm−1; H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H,
1
NH), 7.51 (d, 1H, J = 1.6 Hz), 7.22 (d, 1H, J = 8.4 Hz), 7.10 (dd, 1H, J = 1.6 Hz, J = 8.4
Hz), 6.28 (s, 1H), 4.12 (d, 1H, J = 8.8 Hz), 3.84−3.80 (m, 2H), 3.76 (d, 1H, J = 13.2 Hz),
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3.60 (dd, 1H, J = 2.8 Hz, J = 10.4 Hz), 3.39 (dd, 1H, J = 3.4 Hz, J = 12.0 Hz), 3.60 (dd, 1H,
J = 2.8 Hz, J7 = 10.4 Hz), 3.39 (dd, 1H, J = 3.4 Hz, J = 12.0 Hz), 3.10 (t, 1H, J = 10.4 Hz),
2.34 (s, 1H), 2.22 (s, 1H), 1.28−1.11 (m, 21H), 0.20 (s, 9H) ppm; 13C NMR (100 MHz,
CDCl3) δ 136.7, 134.2, 129.6, 125.8, 122.3, 119.7, 112.0, 102.5, 99.0, 91.5, 80.0, 77.4, 75.9,
72.2, 63.2, 44.1, 18.5, 13.2, −0.2 ppm; HRMS (ESI) calcd. for C28H45ClNO4Si2 [M+H]+
550.2576, found 550.2579.
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3,7ꢀAnhydroꢀ6ꢀCꢀ(5ꢀbromoindolꢀ2ꢀyl)ꢀ1,1,2,2ꢀtetradehydroꢀ1,2,6ꢀtrideoxyꢀ4ꢀOꢀ(triisopro
pylsilyl)ꢀ1ꢀCꢀ(trimethylsilyl)ꢀDꢀglyceroꢀDꢀguloꢀoctitol (3ae). Brown foam, 353 mg, 85%
0
yield; Mp: 96−97 C; Rf = 0.7 (silica gel F254, 1:1, petroleum ether/EtOAc); [α]20D = −34.40
(c 0.50, CHCl3); IR (KBr) 3423, 3134, 2964, 2864, 1664, 1621, 1449, 1400, 1312, 1256,
1141, 1109, 1070, 1022, 882, 802 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 7.66 (s,
1H), 7.23 (dd, 1H, J = 1.6 Hz, J = 8.6 Hz), 7.17 (d, 1H, J = 8.6 Hz), 6.28 (s, 1H), 4.12 (d,
1H, J = 8.4 Hz), 3.81−3.79 (m, 2H), 3.74 (d, 1H, J = 12.4 Hz), 3.60−3.58 (m, 1H), 3.36 (br
d, 1H, J = 9.2 Hz), 3.09 (t, 1H, J = 10.0 Hz), 2.36 (s, 1H), 2.26 (s, 1H), 1.27−1.11 (m, 21H),
13
0.20 (s, 9H) ppm; C NMR (100 MHz, CDCl3) δ 136.6, 134.4, 130.3, 124.8, 122.8, 113.3,
112.4, 102.5, 98.9, 91.5, 80.0, 77.4, 75.8, 72.2, 63.2, 44.0, 18.5, 13.2, −0.2 ppm; HRMS
(ESI) calcd. for C28H45BrNO4Si2 [M+H]+ 594.2070, found 594.2072.
2ꢀ[4ꢀdeoxyꢀ2ꢀOꢀtriisopropylsilylꢀ4ꢀCꢀ(indolꢀ2ꢀyl)ꢀβꢀDꢀglucopyranosyl]indole
(3ba).
0
Brown foam, 329 mg, 88% yield; Mp: 74−75 C; Rf = 0.7 (silica gel F254, 1:1, petroleum
ether/EtOAc); [α]20D = −20.20 (c 0.53, CHCl3); IR (KBr) 3556, 3409, 2962, 2864, 1664,
1619, 1545, 1455, 1400, 1291, 1262, 1130, 1070, 1017, 848, 792 cm−1; 1H NMR (400 MHz,
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CDCl3) δ 8.91, 8.74 (2s, each 1H, 2NH), 7.64−7.59 (m, 2H, H−4, H−4''), 7.31−7.28 (m, 2H,
H−7, H−7''), 7.23−7.11 (m, 4H, H−5, H−5'', H−6, H−6''), 6.54 (s, 1H, H−3), 6.35 (s, 1H,
H−3''), 4.45 (d, 1H, J1', 2' = 8.8 Hz, H−1'), 4.06 (t, 1H, J2', 1' = J2', 3' = 8.8 Hz, H−2'),
3.96−3.91 (m, 1H, H−3'), 3.67−3.59 (m, 2H, H−5', H−6'a), 3.33 (dd, 1H, J6'b, 5' = 2.8 Hz,
J6'b, 6'a =11.6 Hz, H−6'b), 3.21 (t, 1H, J4', 3' = J4', 5' = 10.4 Hz, H−4'), 2.50 (s, 1H, OH),
0.88−0.80 (m, 21H, Si(CH(CH3)2)3) ppm; 13C NMR (100 MHz, CDCl3) δ 136.2, 135.9,
135.6, 135.4 (C−2, C−7a, C−2'', C−7a''), 128.6, 128.0 (C−3a, C−3a''), 122.3, 122.0 (C−6,
C−6''), 120.8, 120.3, 120.2, 119.9 (C−4, C−5, C−4'', C−5''), 111.1, 111.0 (C−7, C−7''), 102.9
(C−3), 99.4 (C−3''), 79.7 (C−5'), 78.7 (C−3'), 77.4 (C−1'), 75.9 (C−2'), 62.9 (C−6'), 45.0
(C−4'), 18.1 (Si(CH(CH3)2)3), 13.1 (Si(CH(CH3)2)3) ppm; HRMS (ESI) calcd. for
C31H43N2O4Si [M+H]+ 535.2992, found 535.2993.
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5ꢀMethylꢀ2ꢀ [4ꢀdeoxyꢀ2ꢀOꢀtriisopropylsilylꢀ4ꢀCꢀ(5ꢀmethylindolꢀ2ꢀyl)ꢀβꢀDꢀglucopyranosyl]
indole (3bb). Brown foam, 354 mg, 90% yield; Mp: 97−100 0C; Rf = 0.7 (silica gel F254, 1:1,
petroleum ether/EtOAc); [α]20D = −23.60 (c 1.61, CHCl3); IR (KBr) 3405, 3165, 3018, 2942,
2864, 1665, 1623, 1458, 1400, 1314, 1258, 1129, 1063, 883, 794 cm−1; 1H NMR (400 MHz,
CDCl3) δ 8.81, 8.68 (2s, each 1H), 7.43, 7.41 (2s, each 1H), 7.21−7.18 (m, 2H), 7.05−7.02
(m, 2H), 6.46 (s, 1H), 6.25 (s, 1H), 4.36 (d, 1H, J = 8.6 Hz, 4.05 (t, 1H, J = 8.6 Hz), 3.88 (br
t, 1H, J = 9.2 Hz), 3.56−3.48 (m, 2H), 3.24 (br d, 1H, J = 9.6 Hz), 3.11 (t, 1H, J = 10.4 Hz),
2.49, 2.48 (2s, each 3H), 0.91−0.83 (m, 21H) ppm; 13C NMR (100 MHz, CDCl3) δ 135.7,
135.5, 134.5, 134.1, 129.4, 128.89, 128.88, 128.3, 123.8, 123.5, 120.4, 119.8, 110.8, 110.7,
102.4, 98.8, 79.6, 78.8, 77.4, 75.6, 62.7, 45.0, 21.64, 21.57, 18.1, 13.0 ppm; HRMS (ESI)
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calcd. for C33H46N2O4Si [M+H]+ 562.3227, found 562.3228.
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5ꢀFluoroꢀ2ꢀ[4ꢀdeoxyꢀ2ꢀOꢀtriisopropylsilylꢀ4ꢀCꢀ(5ꢀfluorolindolꢀ2ꢀyl)ꢀβꢀDꢀglucopyranos
yl]indole (3bc). Brown foam, 335 mg, 84% yield; Mp: 95−97 0C; Rf = 0.7 (silica gel F254,
1:1, petroleum ether/EtOAc); [α]20D = −21.90 (c 1.48, CHCl3); IR (KBr) 3405, 3165, 3018,
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2942, 2864, 1665, 1623, 1458, 1400, 1314, 1258, 1129, 1063, 883, 794 cm−1; H NMR
(400 MHz, CDCl3) δ 9.10, 8.95 (2s, each 1H), 7.25−7.22 (m, 2H), 7.15−7.11 (m, 2H),
6.93−6.88 (m, 2H), 6.48 (s, 1H), 6.29 (s, 1H), 4.46 (d, 1H, J = 8.8 Hz), 4.05 (t, 1H, J =
8.8 Hz), 3.95 (br t, 1H, J = 8.8 Hz), 3.73−3.64 (m, 2H), 3.37 (br d, 1H, J = 9.6 Hz), 3.28
(t, 1H, J = 10.4 Hz), 2.65 (s, 1H), 0.88−0.84 (m, 21H) ppm; 13C NMR (100 MHz, CDCl3)
1
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δ 158.2 (2d, JC−F = 232.0 Hz), 158.0 (2d, JC−F = 232.0 Hz), 137.25, 137.19, 132.7,
3
132.3, 129.0 (2d, 3JC−F = 10.0 Hz), 128.2 (2d, 3JC−F = 10.0 Hz), 111.65 (2d, JC−F = 9.0
Hz), 111.56 (2d, 3JC−F = 10.0 Hz), 110.8(2d, 2JC−F = 26.0 Hz), 110.3 (2d, 2JC−F = 26.0 Hz),
105.4 (2d, 2JC−F = 23.0 Hz), 105.1 (2d, 2JC−F = 23.0 Hz), 103.3, 103.2, 99.43, 99.39, 79.5,
78.8, 77.4, 75.9, 62.8, 44.8, 18.1, 13.1 ppm; 19F NMR (376 MHz, CDCl3) δ −124.1 (dt, J1
= 9.0 Hz, J2 = 4.9 Hz); −124.5 (dt, J1 = 9.4 Hz, J2 = 4.5 Hz) ppm; HRMS (ESI) calcd. for
C31H41 F2N2O4 Si [M+H]+ 571.2804, found 571.2803.
5ꢀChloroꢀ2ꢀ[4ꢀdeoxyꢀ2ꢀOꢀtriisopropylsilylꢀ4ꢀCꢀ(5ꢀchloroindolꢀ2ꢀyl)ꢀβꢀDꢀglucopyranos
yl]indole (3bd). Brown foam, 367 mg, 87% yield; Mp: 49−50 0C; Rf = 0.7 (silica gel F254,
1:1, petroleum ether/EtOAc); [α]20D = −16.50 (c 0.51, CHCl3); IR (KBr) 3405, 3165, 3018,
1
2942, 2864, 1665, 1623, 1458, 1400, 1314, 1258, 1129, 1063, 883, 794 cm−1; H NMR
(400 MHz, CDCl3) δ 8.94, 8.86 (2s, each 1H), 7.55, 7.54 (2s, each 1H), 7.18−7.09 (m,
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4H), 6.46 (s, 1H), 6.31 (s, 1H), 4.51 (d, 1H, J = 8.4 Hz), 4.04−3.96 (m, 2H), 3.78−3.72 (m,
2H), 3.40 (dd, 1H, J= 2.8 Hz, J = 9.2 Hz), 3.29 (t, 1H, J = 10.0 Hz), 0.87−0.84 (m, 21H)
ppm; 13C NMR (100 MHz, CDCl3) δ 136.9, 136.8, 134.5, 134.2, 129.7, 129.0, 126.0,
125.5, 122.7, 122.4, 120.1, 119.8, 112.0, 111.9, 102.6, 99.1, 79.7, 78.5, 77.4, 76.2, 63.0,
44.8, 18.1, 13.1 ppm; HRMS (ESI) calcd. for C31H41Cl2N2O4Si [M+H]+ 603.2213, found
603.2215.
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5ꢀBromoꢀ2ꢀ[4ꢀdeoxyꢀ2ꢀOꢀtriisopropylsilylꢀ4ꢀCꢀ(5ꢀbromoindolꢀ2ꢀyl)ꢀβꢀDꢀglucopyranos
yl]indole (3be). Brown foam, 412 mg, 85% yield; Mp: 95−97 0C; Rf = 0.7 (silica gel F254,
1:1, petroleum ether/EtOAc); [α]20D = −25.80 (c 1.04, CHCl3); IR (KBr) 3405, 3165, 3018,
1
2942, 2864, 1665, 1623, 1457, 1400, 1314, 1258, 1129, 1063, 883, 794 cm−1; H NMR
(400 MHz, CDCl3) δ 9.11, 8.98 (2s, each 1H), 7.71, 7.70 (2s, each 1H), 7.25−7.21 (m,
2H), 7.11−7.08 (m, 2H), 6.43 (s, 1H), 6.26 (s, 1H), 4.43 (d, 1H, J = 8.8 Hz), 4.03 (t, 1H, J
= 8.8 Hz), 3.96−3.91 (m, 1H), 3.69−3.62 (m, 2H), 3.32 (br d, 1H, J = 12.0 Hz), 3.26 (t,
1H, J = 10.4 Hz), 2.64 (br s, 1H), 0.86−0.83 (m, 21H) ppm; 13C NMR (100 MHz, CDCl3)
δ 136.74, 136.69, 134.7, 134.4, 130.3, 129.6, 125.2, 124.9, 123.2, 122.8, 113.4, 113.1,
112.5, 112.4, 102.6, 98.9, 79.5, 78.8, 77.3, 75.8, 62.8, 44.7, 18.1, 13.1 ppm; HRMS (ESI)
calcd. for C31H40Br2N2O4Si [M]+ 690.1124, found 690.1123.
Methyl 4Sꢀ4ꢀCꢀ(5ꢀchloroindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀerythrofuranoside (3ca).
Brown oil, 188 mg, 83% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −45.10 (c 0.56, CHCl3); IR (KBr) 3389, 3046, 2960, 1629, 1599, 1556, 1489,
1
1459, 1377, 1209, 1096, 799 cm−1; H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 7.56 (s,
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1H), 7.27 (d, 1H, J7, 6 = 8.4 Hz), 7.15 (d, 1H, J6, 7 = 8.4 Hz), 6.42 (s, 1H), 5.48 (s, 1H),
5.20 (s, 1H), 4.87 (d, 1H, J3', 2' = 4.8 Hz), 4.28 (br s, 1H), 3.47 (s, 3H), 1.60, 1.37 (2s,
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13
each 3H) ppm; C NMR (100 MHz, CDCl3) δ 138.0, 135.2, 129.3, 125.6, 122.6, 120.2,
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113.0, 112.1, 110.5, 101.0, 85.6, 85.2, 84.00, 55.8, 26.6, 25.1 ppm; HRMS (ESI) calcd.
for C16H19 ClNO4 [M+H]+ 324. 1003, found: 324.1006.
Methyl 4Sꢀ4ꢀCꢀ(indolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀerythrofuranoside (3cb). Brown
oil, 172 mg, 85% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc); [α]20
=
D
−45.10 (c 1.25, CHCl3); IR (KBr) 3444, 3062, 2939, 1625, 1589, 1550, 1491, 1455, 1377,
1
1207, 1097, 799 cm−1; H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H), 7.60 (d, 1H, J = 8.0
Hz), 7.35 (d, 1H, J = 8.0 Hz), 7.20 (t, 1H, J = 7.6 Hz), 7.11 (t, 1H, J =7.6 Hz), 6.47 (s,
1H), 5.50 (s, 1H), 5.19 (s, 1H), 4.88 (d, 1H, J = 5.8 Hz), 4.82 (d, 1H, J = 5.8 Hz), 3.46 (s,
13
3H), 1.59, 1.36 (2s, each 3H) ppm; C NMR (100 MHz, CDCl3) δ 136.9, 136.5, 128.3,
122.4, 120.9, 120.0, 112.9, 115.2, 110.5, 101.6, 85.8, 85.3, 84.2, 55.7, 26.6, 25.1 ppm;
HRMS (ESI) calcd. for C16H20NO4 [M+H]+ 290.1392, found 290.1390.
Methyl 4Sꢀ4ꢀCꢀ(5ꢀmethylindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀerythrofuranoside (3cc).
Brown oil, 191 mg, 90% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −46.80 (c 1.23, CHCl3); IR (KBr) 3387, 3029, 2939, 1627, 1596, 1555, 1492,
1
1458, 1377, 1212, 1097, 795 cm−1; H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.37 (s,
1H), 7.23 (d, 1H, J = 8.2 Hz), 7.01 (d, 1H, J = 8.2 Hz), 6.37 (s, 1H), 5.46 (s, 1H), 5.16 (s,
1H), 4.86 (d, 1H, J = 6.0 Hz), 4.80 (d, 1H, J = 6.0 Hz), 3.44 (s, 3H), 2.44 (s, 3H), 1.57,
1.34 (2s, each 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 136.5, 135.2, 129.1, 128.5, 123.9,
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120.5, 112.8, 110.8, 110.4, 101.0, 85.7, 85.2, 84.2, 55.5, 26.6, 25.1, 21.5 ppm; HRMS
(ESI) calcd. for C17H22NO4 [M+H]+ 304.1549, found 304.1550.
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Methyl 4Sꢀ4ꢀCꢀ(5ꢀfluoroindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀerythrofuranoside (3cd).
Brown oil, 172 mg, 80% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −38.20 (c 1.52, CHCl3); IR (KBr) 3413, 3045, 2957, 1629, 1588, 1553, 1489,
1452, 1377, 1212, 1095, 797 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.96 (s, 1H), 7.25−7.21
(m, 2H), 6.96−6.91 (m, 1H), 6.42 (s, 1H), 5.47 (s, 1H), 5.18 (s, 1H), 4.86 (d, 1H, J = 6.0
Hz), 4.80 (d, 1H, J = 6.0 Hz), 3.46 (s, 3H), 1.58, 1.35 (2s, each 3H) ppm; 13C NMR (100
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MHz, CDCl3) δ 158.0 (d, JC−F = 233.0 Hz), 138.3, 133.4, 128.6 (d, JC−F = 10.0 Hz),
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113.0, 111.7 (d, JC−F = 9.0 Hz), 110.7 (d, JC−F = 26.0 Hz), 110.5, 105.6 (d, 2JC−F = 24.0
4
Hz), 101.5 (d, JC−F = 4.0 Hz), 85.7, 85.2, 84.0, 55.7, 26.6, 25.0 ppm; 19F NMR (376
MHz, CDCl3) δ −124.9 (dt, J1 = 9.3 Hz, J2 = 4.1 Hz) ppm; HRMS (ESI) calcd. for
C16H19FNO4 [M +H]+ 308.1294, found 308.1296.
Methyl 4Sꢀ4ꢀCꢀ(5ꢀbromoindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀerythrofuranoside (3ce).
Brown oil, 213 mg, 83% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −39.30 (c 1.15, CHCl3); IR (KBr) 3406, 3056, 2958, 1624, 1598, 1579, 1485,
1
1456, 1378, 1096, 1055, 795 cm−1; H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.70 (s,
1H), 7.27−7.20 (m, 2H), 6.39 (s, 1H), 5.45 (s, 1H), 5.17 (s, 1H), 4.84 (d, 1H, J = 5.8 Hz),
4.79 (d, 1H, J = 5.8 Hz), 3.45 (s, 3H), 1.56, 1.34 (2s, each 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 137.8, 135.4, 130.0, 125.1, 123.3, 113.1, 113.0, 112.6, 110.5, 100.9, 85.6, 85.2,
83.9, 55.7, 26.6, 25.0 ppm; HRMS (ESI) calcd. for C16H19BrNO4 [M+H]+ 368.0497,
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found 368. 0499.
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Methyl 4Sꢀ4ꢀCꢀ(5ꢀfluoroindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀαꢀLꢀerythrofuranoside (3da).
Pale yellow oil, 165 mg, 78% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −230 (c 0.50, CHCl3); IR (KBr) 3337, 3048, 2926, 1626, 1586, 1542, 1485, 1457,
1380, 1090, 1026, 800 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H, NH), 7.30−7.22
(m, 2H, H−4, H−7), 6.96−6.91 (m, 1H, H−6), 6.52 (s, 1H, H−3), 5.15 (d, 1H, J4', 3' = 3.2
Hz, H−4'), 5.00 (s, 1H, H−1'), 4.86 (dd, 1H, J3', 4' = 3.2 Hz, J3', 2' = 5.6 Hz, H−3'), 4.69 (d,
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1H, J2', 3' = 5.6 Hz, H−2'), 3.40 (s, 3H, OCH3), 1.60, 1.34 (2s, each 3H, 2CH3) ppm; C
NMR (100 MHz, CDCl3) δ 158.0 (C−5, d, 1JC−F = 232.0 Hz), 134.2 (C−2), 133.2 (C−7a),
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127.9 (C−3a, d, JC−F = 10.0 Hz), 113.0 (isopropylidene−C), 111.9 (C−7, d, JC−F = 9.6
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Hz), 110.9 (C−6, d, JC−F = 26.3 Hz), 107.1 (C−1'), 105.5 (C−4, d, JC−F = 23.3 Hz),
103.3 (C−3, d, 4JC−F = 4.5 Hz), 85.5 (C−2'), 81.7 (C−3'), 75.2 (C−4'), 55.2 (OCH3), 26.4,
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24.6 (2CH3) ppm; F NMR (376 MHz, CDCl3) δ −124.9 (dt, J1 = 9.3 Hz, J2 = 4.1 Hz)
ppm; HRMS (ESI) calcd. for C16H19FNO4 [M+H]+ 308.1294, found 308.1292.
Methyl 4Sꢀ4ꢀCꢀ(indolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀαꢀLꢀerythrofuranoside (3db). Brown
oil, 157 mg, 73% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc); [α]20
=
D
−25.00 (c 0.5, CHCl3); IR (KBr) 3447, 3032, 2926, 1624, 1591, 1557, 1491, 1450, 1378,
1
1231, 1096, 802 cm−1; H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 7.60 (d, 1H, J = 7.6
Hz), 7.37 (dd, 1H, J = 8.0 Hz, J = 0.8 Hz), 7.18 (dt, 1H, J = 8.0 Hz, J = 0.9 Hz), 7.08 (dt,
1H, J = 8.0 Hz, J = 0.8 Hz), 6.56 (s, 1H), 5.18 (d, 1H, J = 3.4 Hz), 5.00 (s, 1H), 4.86 (dd,
1H, J = 3.4 Hz, J = 5.6 Hz), 4.69 (d, 1H, J = 5.6 Hz), 3.40 (s, 3H), 1.60, 1.34 (2s, each 3H)
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ppm; 13C NMR (100 MHz, CDCl3) δ 136.7, 132.4, 127.6, 122.4, 120.9, 119.8, 112.9,
111.3, 107.1, 103.3, 85.5, 81.8, 75.4, 55.1, 26.4, 24.6 ppm; HRMS (ESI) calcd. for
C16H20NO4 [M+H]+ 290.1392, found 290.1391.
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Methyl 4Sꢀ4ꢀCꢀ(5ꢀmethylindolꢀ2ꢀyl)ꢀ2,3ꢀOꢀisopropylideneꢀαꢀLꢀerythrofuranoside (3dc).
Yellow oil, 151 mg, 75% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −9.00 (c 0.50, CHCl3); IR (KBr) 3457, 3048, 2925, 1627, 1589, 1556, 1483, 1459,
1
1379, 1163, 1100, 1020, 801 cm−1; H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 7.37 (s,
1H), 7.25 (d, J = 8.0 Hz), 7.00 (d, 1H, J = 8.0 Hz), 6.47 (s, 1H), 5.15 (d, 1H, J= 3.2 Hz),
4.99 (s, 1H), 4.85 (dd, 1H, J = 3.2 Hz, J = 5.6 Hz), 4.68 (d, 1H, J = 5.6 Hz), 3.40 (s, 3H),
13
2.43 (s, 3H), 1.60, 1.33 (2s, each 3H) ppm; C NMR (100 MHz, CDCl3) δ 135.1, 132.4,
128.9, 127.9, 124.1, 120.5, 112.7, 110.9, 107.1, 102.8, 85.5, 81.8, 75.4, 55.1, 26.4, 24.6,
21.6 ppm; HRMS (ESI) calcd. for C17H22NO4 [M+H]+ 304.1549, found 304.1548.
4Sꢀ4ꢀCꢀ(5ꢀfluoroindolꢀ2ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylideneꢀαꢀLꢀthreofuranoside
(3ea). Pale yellow oil, 195 mg, 73% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum
ether/EtOAc); [α]20D = −55.00 (c 0.48, CHCl3); IR (KBr) 3442, 3058, 2926, 1625, 1589,
1
1549, 1488, 1456, 1378, 1261, 1081, 801 cm−1; H NMR (400 MHz, CDCl3) δ 8.72 (s,
1H, NH), 7.36−7.18 (m, 5H, H−4, H−7, 3ArH), 7.01 (d, 2H, J = 6.8 Hz, 2ArH), 6.93 (t,
1H, J = 9.2 Hz, H−7), 6.48 (s, 1H, H−3), 6.06 (d, 1H, J1', 2' = 3.4 Hz, H−1'), 5.39 (s, 1H,
H−4'), 4.75 (d, 1H, J2', 1' = 3.4 Hz, H−2'), 4.44 (d, B of AB, 1H, J = 11.2 Hz, Ph−CHB),
4.18 (d, A of AB, 1H, J = 11.2 Hz, Ph−CHA), 4.08 (s, 1H, H−3'), 1.59, 1.38 (2s, each 3H,
1
2CH3) ppm; 13C NMR (100 MHz, CDCl3) δ 158.0 (C−5, d, JC−F = 232.0 Hz), 137.0
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(aromatic−C), 134.2 (C−2), 133.0 (C−7a), 128.6, 128.3, 128.01 (5 aromatic−CH), 127.95
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(C−3a, d, JC−F = 11.2 Hz), 112.1 (isopropylidene−C), 111.7 (C−7, d, JC−F = 10.0 Hz),
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110.7 (C−6, d, JC−F = 26.0 Hz), 105.5 (C−4, d, 2JC−F = 23.0 Hz), 104.8 (C−1'), 102.3
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(C−3, d, 4JC−F = 5.0 Hz), 84.2 (C−3'), 83.1 (C−2'), 76.2 (C−4'), 72.9 (PhCH2O), 27.0, 26.3
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(2CH3) ppm; F NMR (376 MHz, CDCl3) δ −125.0 (dt, J1 = 9.2 Hz, J2 = 4.1 Hz) ppm;
HRMS (ESI) calcd. for C21H21FNO4 [M+H]+ 370.1455, found 370.1452.
4Sꢀ4ꢀCꢀ(indolꢀ2ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylideneꢀαꢀLꢀthreofuranoside (3eb). Pale
yellow oil, 196 mg, 77% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −31.00 (c 0.52, CHCl3); IR (KBr) 3395, 3055, 2940, 1646, 1597, 1561, 1523,
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1492, 1374, 1214, 1086, 803 cm−1; H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 7.62 (d,
1H, J = 7.6 Hz), 7.31−6.39 (m, 8H), 6.54 (s, 1H), 6.08 (d, 1H, J = 3.2 Hz), 5.42 (br s, 1H),
4.76 (s, 1H, J = 3.2 Hz), 4.42 (d, 1H, J = 11.2 Hz), 4.20 (d, 1H, J = 11.2 Hz), 4.08 (d, 1H,
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J = 2.0 Hz), 1.60, 1.38 (2s, each 3H) ppm; C NMR (100 MHz, CDCl3) δ 137.0, 136.5,
132.4, 128.6, 128.2, 128.0, 127.7, 122.2, 120.8, 119.7, 112.0, 115.2, 104.7, 102.4, 84.3,
83.2, 76.4, 72.9, 27.0, 26.3 ppm; HRMS (ESI) calcd. for C21H22NO4 [M+H]+ 352.1549,
found 352.1547.
5Rꢀ5ꢀCꢀ(indolꢀ2ꢀyl)ꢀ1,2;3,4ꢀdiꢀOꢀisopropylideneꢀβꢀLꢀarabinopyranose (3fa). Pale
yellow oil, 198 mg, 82% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −123.00 (c 0.50, CHCl3); IR (KBr) 3473, 3030, 2927, 1619, 1601, 1558, 1498,
1458 , 1381, 1260, 1093, 800 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 1H,NH), 7.58
(d, 1H, J4, 5 = 7.6 Hz, H−4), 7.37 (d, 1H, J7, 6 = 7.6 Hz, H−7), 7.17 (t, 1H, J6, 5 =J6, 7 = 7.6
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Hz, H−6), 7.08 (t, 1H, J5, 4 = J5, 6 = 7.6 Hz, H−5), 6.48 (s, 1H, H−3), 5.66 (d, 1H, J1', 2'
4.8 Hz, H−1'), 5.11 (s, 1H, H−5'), 4.73 (d, 1H, J3', 4' = 7.6 Hz, H−3'), 4.52 (d, 1H, J4', 3'
=
=
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7.6 Hz, H−4'), 4.39 (br d , 1H, H−2'), 1.63, 1.59, 1.39, 1.38 (4s, each 3H, 4 CH3) ppm;
13C NMR (100 MHz, CDCl3) δ 136.2 (C−7a), 134.6 (C−2), 127.8 (C−3a), 122.1 (C−6),
120.8 (C−4), 119.7 (C−5), 111.3 (C−7), 109.6, 108.9 (2 isopropylidene−C), 101.7 (C−3),
96.8 (C−1'), 73.8 (C−4'), 71.1 (C−3'), 70.9 (C−2'), 64.4 (C−5'), 26.4, 26.2, 25.1, 24.1 (4
CH3) ppm; HRMS (ESI) calcd. for C19H24NO5 [M+H]+ 346.1654, found 346.1652.
5Rꢀ5ꢀCꢀ(5ꢀmethylindolꢀ2ꢀyl)ꢀ1,2;3,4ꢀdiꢀOꢀisopropylideneꢀβꢀLꢀarabinopyranose (3fb).
Pale yellow oil, 213 mg, 85% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −168.00 (c 0.46, CHCl3); IR (KBr) 3454, 3024, 2926, 1613, 1588, 1568, 1464,
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1456, 1380, 1212, 1068, 800 cm−1; H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 7.36 (d,
1H), 7.25 (d, 1H, J = 8.8 Hz), 6.99 (d, 1H, J = 8.8 Hz), 6.39 (s, 1H), 5.65 (d, 1H, J = 4.8
Hz), 5.08 (s, 1H), 4.72 (d, 1H, J = 8.0 Hz), 4.50 (d, 1H, J = 8.0 Hz), 4.38 (d, 1H, J = 4.8
Hz), 2.43 (s, 3H), 1.63, 1.58, 1.39, 1.37 (4s, each 3H) ppm; 13C NMR (100 MHz, CDCl3)
δ 134.7, 134.6, 128.8, 128.0, 123.8, 120.4, 110.9, 109.5, 108,9, 101.3, 96.8, 73.8, 71.1,
70.9, 64.4, 26.5, 26.2, 25.1, 24.1, 21.6 ppm; HRMS (ESI) calcd. for C20H26NO5 [M+H]+
360.1811, found 360.1814.
5Rꢀ5ꢀCꢀ(5ꢀfluoroindolꢀ2ꢀyl)ꢀ1,2;3,4ꢀdiꢀOꢀisopropylideneꢀβꢀLꢀarabinopyranose (3fc).
Pale yellow oil, 203 mg, 80% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −131.20 (c 1.39, CHCl3); IR (KBr) 3472, 3032, 2929, 1623, 1589, 1548, 1487,
1456, 1380, 1212, 1070, 800 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.29−7.22
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(m, 2H), 6.95−6.90 (m, 1H), 6.45 (s, 1H), 5.67 (d, 1H, J = 4.8 Hz), 5.10 (br s, 1H), 4.74
(dd, 1H, J = 2.2 Hz, J = 8.0 Hz), 4.51 (dd, 1H, J = 1.2 Hz, J = 8.0 Hz), 4.41 (dd, 1H, J=
4.8 Hz, J = 2.2 Hz), 1.63, 1.58, 1.40, 1.38 (4s, each 3H) ppm; 13C NMR (100 MHz,
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CDCl3) δ 157.9 (d, JC−F = 233.0 Hz), 136.4, 133.0, 128.0 (d, JC−F = 10.0 Hz), 111.8 (d,
3JC−F = 9.0 Hz), 110.5 (d, JC−F = 26.0 Hz), 109.6, 109.0, 105.4 (d, 2JC−F = 23.0 Hz),
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101.6 (d, JC−F = 5.0 Hz), 96.8, 73.6, 71.0, 70.8, 64.3, 26.4, 26.1, 25.0, 24.0 ppm; 19F
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NMR (376 MHz, CDCl3) δ −125.0 (dt, J1 = 9.3 Hz, J2 = 4.1 Hz) ppm; HRMS (ESI) calcd.
for C19H23FNO5 [M+H]+ 364.1560, found 364.1563.
5Rꢀ5ꢀCꢀ(5ꢀchloroindolꢀ2ꢀyl)ꢀ1,2;3,4ꢀdiꢀOꢀisopropylideneꢀβꢀLꢀarabinopyranose (3fd).
Brown oil, 223 mg, 84% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −174.40 (c 0.83, CHCl3); IR (KBr) 3458, 3054, 2929, 1613, 1580, 1553, 1482,
1463, 1381, 1212, 1069, 801 cm−1; H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.52 (d,
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1H, J = 1.4 Hz), 7.25 (d, 1H, J = 8.8 Hz), 7.09 (dd, 1H, J = 2.0 Hz, J = 8.8 Hz), 6.40 (s,
1H), 5.63 (d, 1H, J = 4.8 Hz), 5.06 (s, 1H), 4.70 (dd, 1H, J = 2.1 Hz, J = 8.0 Hz), 4.48 (dd,
1H, J = 8.0 Hz, J = 1.6 Hz), 4.38 (dd, 1H, J = 4.8 Hz, J = 2.1 Hz), 1.60, 1.55, 1.36, 1.35
(4s, each 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 136.1, 134.5, 128.8, 125.3, 122.4,
120.0, 112.2, 109.6, 109.0, 101.2, 96.8, 73.5, 71.0, 70.8, 64.3, 26.4, 26.2, 25.0, 24.0
ppm; HRMS (ESI) calcd. for C19H23ClNO5 [M+H]+ 380.1265, found 380.1268.
5Rꢀ5ꢀCꢀ(5ꢀbromoindolꢀ2ꢀyl)ꢀ1,2;3,4ꢀdiꢀOꢀisopropylideneꢀβꢀLꢀarabinopyranose (3fe).
Yellow oil, 258 mg, 87% yield; Rf = 0.6 (silica gel F254, 3:1, petroleum ether/EtOAc);
[α]20D = −137.80 (c 0.54, CHCl3); IR (KBr) 3452, 3058, 2928, 1649, 1577, 1542, 1486,
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