Iodosobenzene diacetate-Iodine and IBX-Iodine: Reagent systems for the synthesis of diastereomerically enriched 2-deoxy-2-iodoglycosyl acetates and 2-deoxy-2-iodoglycosyl ortho-iodobenzoates from protected glycals

Article abstract of DOI:10.1016/j.tet.2017.06.001

Two efficient, metal free reagent systems, PhI(OAc)₂-I₂ (method A) and IBX-I₂ (method B), for stereoselective synthesis of trans-2-deoxy-2-iodoglycosylacetates and O-iodobenzoates respectively from differently protected glycals have been developed. They are compatible with a variety of protecting groups and various functional groups at 2C-position. Hexose-3,2-enolone 8 is obtained directly from 2-acetoxy glycal 5 by method A. An application to modified method B has been shown by synthesis of a diastereomerically pure α-glycosyl ortho-hexynylbenzoate 12, a glycosyl donor from 3,4,6-tri-O-acetyl-D-glucal in two steps that has been further utilized in the synthesis of glycosides 13–18.

Full text of DOI:10.1016/j.tet.2017.06.001

Accepted Manuscript
Iodosobenzene diacetate-Iodine and IBX-Iodine: Reagent systems for the synthesis
of diastereomerically enriched 2-deoxy-2-iodoglycosyl acetates and 2-deoxy-2-
iodoglycosyl ortho-iodobenzoates from protected glycals
Puli Saidhareddy, Sama Ajay, Arun K. Shaw
PII:
S0040-4020(17)30620-8
10.1016/j.tet.2017.06.001
TET 28766
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 March 2017
Revised Date: 31 May 2017
Accepted Date: 3 June 2017
Please cite this article as: Saidhareddy P, Ajay S, Shaw AK, Iodosobenzene diacetate-Iodine and
IBX-Iodine: Reagent systems for the synthesis of diastereomerically enriched 2-deoxy-2-iodoglycosyl
acetates and 2-deoxy-2-iodoglycosyl ortho-iodobenzoates from protected glycals, Tetrahedron (2017),
doi: 10.1016/j.tet.2017.06.001.
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Iodosobenzene diacetate-Iodine and IBX-Iodine:
Reagent systems for the synthesis of diastereomerically
enriched 2-deoxy-2-iodoglycosyl acetates and
2-deoxy-2-iodoglycosyl ortho-iodobenzoates from
protected glycals.
Leave this area blank for abstract info.
ACCEPTED MANUSCRIPT
Puli Saidhareddy, Sama Ajay and Arun K. Shaw
Division of Medicinal and Process Chemistry,
Central Drug Research Institute (CDRI), CSIR, Lucknow 226 031, India
PO
PO
OP
I
O
I
O
PO
PO
O
PO
PO
PO
PO
BAIB/I2
IBX/I2
DCM, rt, 73%
DCM, rt, 30 min,
R1
2
11
O
O
R1
1
OAc
Upto 75% yield
and
-manno: -gluco
ratio 98:2
P= protecting group,
R1=H, OAc, I, C=C
I
R1=H, I, C=C
Upto 97% yield and
-manno: -gluco ratio 96:4
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
0

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Iodosobenzene diacetate-Iodine and IBX-Iodine: Reagent systems for the
synthesis of diastereomerically enriched 2-deoxy-2-iodoglycosyl acetates and 2-
deoxy-2-iodoglycosyl ortho-iodobenzoates from protected glycals
Puli Saidhareddy, Sama Ajay and Arun K. Shaw
Division of Medicinal and Process Chemistry, Central Drug Research Institute (CDRI), CSIR, Lucknow 226 031, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Two efficient, metal free reagent systems, PhI(OAc)2-I2 (method A) and IBX-I2
(method B), for stereoselective synthesis of trans-2-deoxy-2-iodoglycosylacetates and
O-iodobenzoates respectively from differently protected glycals have been developed.
They are compatible with a variety of protecting groups and various functional groups
at 2C-position. Hexose-3,2-enolone 8 is obtained directly from 2-acetoxy glycal 5 by
method A. An application to modified method B has been shown by synthesis of a
diastereomerically pure α-glycosyl ortho-hexynylbenzoate 12, a glycosyl donor from
Available online
Keywords:
3,4,6-tri-O-acetyl-
D-glucal in two steps that has been further utilized in the synthesis
2-deoxyglycosides
Iodoacetoxylation
Glycals
of glycosides 13-18.
Hypervalent iodine reagents
Glycosylation
2009 Elsevier Ltd. All rights reserved
.
1. Introduction
because of the green nature of the iodine over the others.
Moreover, as a radical precursor it also provides the basis for
introduction of alkenyl substituents.13 The stereoselective
preparation of 2-deoxy-2-iodoglycopyranosyl acetates can be
accomplished in three different ways. The first one involves
nucleophilic displacement of 2-triflates with any suitable
nucleophile.14 Second approach proceeds through the formation
of halohydrins from protected glycals followed by acetylation to
give isomeric mixtures. The low diastereoselectivity of
halohydrin formation demerits this method.15 Formation of
haloacetates from protected glycals directly falls under the third
category.16 Among them, last one continues to attract many
carbohydrate chemists because the formation of desired product
takes place with high yields and excellent stereoselectivity.
The biological significance of many natural products has been
found to be due to the presence of 2-deoxy and 2,6-dideoxy
glycosides.1 These are also structurally important components for
the stereoselective synthesis of glycosides found in several
important natural products such as the angucycline family of
antibiotics (landomycin A),2 aureolic acid antibiotics (olivomycin
A, chromomycin A3),3 enediynes (calicheamycin γ1 ,
I
esperamicins A1 and C),4 antiparacital glycosides, avermectins
(avermectin B1a, ivermectin),5 some cholestane glycosides
(OSW-1),6 and cardiac glycosides (digitoxine)7 (Fig. 1).
Removing of these deoxy sugars from the above clinically
important molecules often harshly decreases their efficacy and/or
specificity. 2-Deoxysugars also play a key role in glycolipids,
glycoproteins, and lipopolysaccharides, where they act as ligands
for cell-cell interactions or as targets for toxins, antibodies, and
microorganisms.8 The above compounds contain monosaccharide
units belonging to the both
configurations (Figure 1).
D and L series with all possible
The stereo controlled construction of glycosidic linkage in the
absence of a stereo directing group at C-2 position in 2-deoxy-
oligosaccharides becomes one of the most challenging tasks in
glycosylation reactions.9 This problem can be overcome by using
electron donating groups (such as iodo, phenylselenyl10 and
phenylsulfanyl11) as stereo directing groups at position 2 of
glycosyl donor in glycosylation step. The 2-heteroatomic-
substituted glycosides can be further reduced to deliver
corresponding 2-deoxyglycosides.12 In this regard, iodoglycosyl
Figure 1: Some biologically important 2-deoxyoligosaccharides containing
configurationally different 2-deoxy sugars.
derivatives are very important in preparation of oligosaccharides,
———
Corresponding author. Tel.: +919415403775; fax: +91(522)2623405; e-mail: akshaw55@yahoo.com
1

Kirschning et al reported the reactivity of hypervalent iodine and
ACCEPTED MANUSCRIPT
its potential applications in the 1,2-cohalogenation of C–C
multiple bonds and glycal substrates.16a,17 Hotha and his
coworkers investigated the regioselective 1,2-functionalization of
glycals using cetylammonium bromide (CTAB) in the presence
of critical micelle concentration conditions in combination with
trivalent iodine PhI(OAc)2 (BAIB).16f The hypervalent iodine
compound, BAIB along with phosphinic acid16a or trimethylsilyl
iodide16j were used together for iodophosphoryloxylation and
iodoacetoxylation of glycals respectively. Other reagents that
include CAN (ceric ammonium nitrate)/NaI/AcOH,16e IDCP
Scheme 1: Iodoacetoxylation of glycal 1a using BAIB-I2-TBHP.
Next, we used BAIB-I2 system in the absence of TBHP and
gratifyingly the reaction was found to be clean (TLC) due to
complete consumption of 1a in just 30 min to afford separable
diastereomeric mixture of 2a and 3a in a ratio of 95:5 with 93%
yield. We carried out several pilot experiments to optimize the
reaction conditions by screening different solvents at various
temperatures with varying ratios of 1a and BAIB-I2.The most
satisfactory yield of the desired products 2a and 3a with a 95:5
ratio of manno-gluco isomers was 93% when 1.0 mmol of 1a was
treated with 0.6 mmol of BAIB and 1.2 mmol of I2 at 25 °C for
30 min (Table 1, entries 1-5). It was found that the reaction in
DCM at room temperature proceeded smoothly without
formation of any side products whereas the reaction in THF and
acetonitrile took more time (30-90 min) to complete the reaction
with poor yield of 2a and 3a. The reaction in solvents like
toluene and DMF was unsuccessful (Table 1, entries 5-9).
Having established optimized conditions (Table 1 entry 3), we
further proceeded to examine the scope of differently protected
glycals including pentose sugars and with variable 2C-branched
hex-2-enopyranosides to obtain the corresponding isomeric
iodoacetates (Table 2). As expected, we found that a wide array
of masked glycals bearing different protecting groups (acetyl,
benzyl, sillyl, MOM) showed good compatibility in this
transformation. The complete conversion of each glycal was
noticed in just 30 min and their corresponding products 2a-2o
were obtained in good to excellent yields with varying α/β ratios
under the optimized condition (Table 2, entries 1-11).
(iodonium dicollidine perchlorate)/NIS (N-iodosuccinimide),15b
18h
KIO3/AcOH,18f
CuI/NaIO4
NH4I/H2O2/Ac2O,16d
and
I2/Cu(OAc)2 ,
16h
promoted the iodoacetoxylation of glycals and
alkenes.
During the past two decades, the versatility of hypervalent iodine
or organo iodine reagents in organic synthesis has been well
recognized owing to their mildness and selectively effecting a
number of oxidative transformations.19 Currently, both iodine
(III) and iodine (V) are widely used in organic synthesis (fig.2).
An important feature of these molecules is their ability to transfer
ligands that are attached to central iodine atom onto appropriate
electrophiles. The electrophilic halogenation of olefins by the
combination of these reagents with halide salts, followed by
nucleophilic-assisted halonium ion ring opening has been well
documented in the literature.20 The application of organo iodine
reagents (fig. 2) on fully protected glycals has been shown for
selective C3-O-oxidation, C-2 heteroatom substitution and
oxidative glycosidation.21 Herein, we have demonstrated a new
method for the synthesis of 2-deoxy-2-iodoglycosyl acetate and
2-iodobenzoates using BAIB-I2 and IBX-I2 systems respectively.
Table 1: Optimization of reaction condition.
yield (%) and
BAIB
(eq)
I2
(eq)
Entry
Temp
Solvent
ratio
(manno:gluco)a
93%, 95:5
93%, 95:5
93%, 95:5
93%, 95:5
80%, 90:10
85%, 90:10
70%, 90:10
-
Figure.2: Hypervalent iodine (IIII and IV) reagents.
1
2
3
4
5
6
7
8
9
1.2
1.0
0.6
0.6
0.6
0.6
0.6
0.6
0.6
1.5
1.2
1.2
1.2
rt
rt
rt
DCM
DCM
DCM
DCM
DCM
MeCN
THF
2. Results and Discussion
We initiated our work with an aim to search for a suitable reagent
system for iodoacetoxylation of globally protected glycals. In our
initial experiments, 1 mmol of per-O-acetyl glucal 1a was treated
0 °C
1.2 reflux
12
1.2
1.2
1.2
rt
rt
rt
rt
with
1.2
mmol
of
PhI(OAc)2
or
BAIB
([bis(acetoxy)iodo]benzene,), 1.2 mmol of iodine (I2) and 0.2
mmol of t-butyl hydroperoxide (TBHP, for radical initiation) in 5
mL of dichloromethane at 0 °C. We observed the formation of a
complex mixture of pyranosyl acetates α-manno 2a and β-gluco
3a and 2-iodoglucal 4 by their 1H NMR and MS analyses
(Scheme 1). On replacement of more reactive molecular iodine
with NIS in the above reaction, we observed that 1a was not
consumed at 0°C. However, performing the reaction at refluxing
temperature led to the formation of chromatographically
inseparable materials.
Toluene
DMF
-
ayields and ratios are calculated after column purification
In the case of 6-O-t-butyldiphenyl silyl protected glycals 1e and
1f, the α/β diastereomeric ratios of the desired products were
slightly lower than those derived from acetyl (1a, 1c) and benzyl
(1b, 1d) protected glycals. Here we wish to mention that the title
reaction with 1g and 1h (D-arabinals) led to the formation of
their respective α/β anomers 96% and 90% yields with
1
diastereomeric ratios 88:12 and 86:14. The C4 conformation of
the major 1,2- dieqatorial isomer 2h was established by its
1
detailed H and NOESY spectroscopy. Here the anomeric proton
appeared at δ 5.89 ppm (d, J1,2= 8.5 Hz), H2 at δ 4.33 ppm (dd,
J2,1= 8.7 Hz and J2,3= 10.0 Hz) ,H3 at δ 3.55 ppm (dd, J2,3= 10.0
Hz and J3,4= 3.0 Hz) and its NOESY experiment showed
correlation between H1-H3, H1-H5' (C5 axial proton), and H3-
2

ACCEPTED MANUSCRIPT
Table 2: Reactions of various glycals with reagent system BAIB-I2a
bYield
&
bYield
&
Entry
Substrate
Product
Entry
Substrate
Product
cratios
cratios
(α/β)
(α/β)b
93%
95:5
95%
90:10
1
2
3
4
10
95%
90:10
98%
80:20
11
96%
92:8
95%
96:4
12
97%
90:10
13
no reaction
TBDPSO
MOMO
MOMO
O
90%
85:15
75%
80:20
5
6
14
15
1e
AcO
I
AcO
AcO
O
87%
89:11
85%
85:15
OAc
NC
2o
96%
88:12
7
8
16
17
97%
81%
90%
86:14
OAc
90%
80:20
O
9
AcO
AcO
2i
I
b
aReaction conditions: glycals (1 eq), BAIB (0.6 eq), I2 (1.2 eq), dry DCM, 25 °C, 30 min, isolated yields after purification by
silica gel column chromatography, cisomeric ratios were determined by 1H NMR of the crude sample .
on 3,4-dihydropyran 1p and cyclohexene 1q to accesses their
H5' protons. Similarly the identification of 2g was established by
respective derivatives 2p (97%) and 2q (81%). Unfortunately the
reaction was futile with 2-nitroglycals24 1m both at room
temperature and with heating.
analogy. The title reaction with acetylated
L-rhamnal 1i prepared
from -rhamnose, furnished the α/β anomers in the ratio of 80:20
L
1
(90%). Here the major isomer 1,2-diaxial iodoacetate 2i with C4
conformation was established on the basis of its proton NMR
spectra (1H appeared singlet at δ 6.27 ppm) and previous
O
OAc
O
O
O
OAc
I
AcO
AcO
PhI(OAc)2, I2
AcO
AcO
AcO
AcO
reports.16b The reaction with
D-ribose derived furanoid glycals 1j
DCM, RT
30 min.,
OAc
OAc
and 1k22 gave their respective iodoacetates 2j and 2k with
excellent yields and diastereomeric ratios. We have also executed
the title reaction with different 2-substituted glycals (1l-1o).23
While the reaction was successful with the 2-iodoglucal23 1l to
give 2-deoxy-2,2-diiodoglycosyl acetate 2l in 95% yield,
iodoacetoxylation of 2C-pseudoglycals 1n and 1o, took place
regioselectively at endocyclic glycosyl 1,2-double bond to
furnish the corresponding 1-acetoxy-2-iododerivatives 2n and 2o
in moderate yields. We also fruitfully applied this reagent system
OAc
7
OAc
5
OAc
6
O
OAc
O
AcO
silica gel
AcO
8
Scheme 2: Synthesis of enolone 8 from 2-acetoxyglycal 5.
In addition, when 2-acetoxy-peracetylated-
subjected to this reaction, in contrast to above examples (Table
D
-glucal 525 was
3

2), it took more equivalents of BAIB (1.2 equiv) for complete
ACCEPTED MANUSCRIPT
consumption of the starting material. The purification of the
crude product mixture with silica gel column chromatography
afforded an unexpected 3,2-enolone 8 (Scheme 2). After
thorough literature search,26 we assumed that 8 was obtained
through an expected iodoacetoxylated intermediate 6, which on
β-elimintion via a corresponding enolate derivative of 7. Our
assumption was based on its crude HRMS spectrometry which
showed m/z peak at 346.26 Finally, the intermediate 7 on silica gel
column chromatography gave pyranoid enolone 8 in 72% yield.
It was characterized by its NMR and HRMS spectrometry and
the data were found to be consistent with the reported.26c
69%
90:10
4
O
O
I
O
I
65%
92:8
OAc
5
6
OAc
11e
75%
93:7
aReaction conditions: glycals (1 eq), IBX (1.5 eq), I2 (1.2 eq), dry
b
1
DCM, 25 °C, 45 min, isomeric ratios were determined by H
NMR of the crude sample.
Next, when we attempted the oxidation of 1a with IBX-I2 which
does not contain any acetoxy functional ligands, α-manno isomer
11a was obtained exclusively in 74% yield (98:2, α/β ratio) in 45
min. To test the susceptibility of the reaction with different
protecting groups, the reaction was further extended to other
differently protected pyranoid glycals 1b,1c, 1f, 1g and furanoid
glycal 1k to obtain their respective 2-deoxy-2-iodo-(2-
iodobenzyloxy) glycosylates (11b-11f) in good yields and with
excellent α-manno selectivity (Table 3).
Scheme 3: Reactions of tri-O-acetylated D-glucal with different hypervalent
iodine reagents.
Encouraged by the above findings, our attention turned toward to
realize the scope of different hypervalent iodine (both IIII and IV)
reagents on peracetylated-D-glucal 1a (Scheme 3). Thus, the
reaction of 1a with BTI and I2 at room temperature furnished an
inseparable mixture of α-manno and β-gluco isomers 9 and 10 in
85% with 90:10 ratio (HPLC). But the reaction of 1a with
Koser’s reagent (HTI) and I2 was futile and the starting material
was remain unchanged. Dess-Martin periodinane (DMP)
mediated oxidation of 1a furnished a separable mixture of 2a and
3a (52%) along with a considerable amount of 2-iodo-2-deoxy-
glycosylester of 2-iodobenzoic acid 11a in 25% yield (Scheme
3). It was obtained by stereoselective opening of iodonium
intermediate by nucleophilic attack of a bidentate ligand 2-
To the best of our knowledge, this is the first report on transfer of
bidentate ligand of hypervalent iodine reagent (IV, DMP or IBX)
to electron rich double bond in molecules like glycals. To
exemplify the synthetic utility of 2-deoxy-2-iodo glycosyl
benzoates 11, we chose 11a as an example which was subjected
to palladium catalyzed (PdCl2(PPh3)2) Sonogashira coupling with
n-hexyne to obtain glycosyl ortho-hexynyl benzoate 12 in 85%.27
These n-hexynyl benzoates can be used as a glycosyl donor for
the complex oligosaccharide synthesis by using Gold (I)
catalyst.28 In contrast to previous reports28 where they used three
step process i.e., Sonogashira coupling of n-hexyne with methyl
2-iodobenzoate followed by ester hydrolysis and condensation of
the resulting acid with globally protected lactol derivatives to
prepare racemic mixture of α/β glycosyl ortho-hexenyl
benzoates, herein we synthesized the diastereomerically pure α-
glycosyl ortho-hexenyl benzoate 12 in two steps (Scheme 4) in
stereoselective manner. The benzoate 12 was tested for
glycosylation with different acceptors like benzyl alcohol, sugar
(glucose)29 and amino acid (Phenylglycine)30 derived primary
alcohols in presence of catalyst PPh3AuNTf2 (0.1 equiv) in DCM
at -78 °C to rt to obtain their respective glycoside.28c The
glycosylation reaction was also successful with acceptors like 4-
methoxyphenol and secondary alcohols isopropanol and glucose
iodobenzoic acid.
Table 3: Reactions of various glycals with the reagent system IBX-I2a
Yield (%)
Entry
1
Substrate
Product
& ratio
(α/β)b
AcO
AcO
I
O
I
74%
98:2
AcO
O
11a
O
79%
98:2
2
3
derived acceptors (4-methoxyphenyl 2,4.6-tri-O-benzyl-α-D-
gucopyranoside) to produce the α-glycosides 16, 17 and 18
respectively. In all the cases, we observed only α-diastereomer of
the corresponding glycosides 13-18 in 85-92% yields (Scheme
4).
73%
98:2
4

5
dominantly adopts the H4 half-chair conformation, from which
ACCEPTED MANUSCRIPT
the formation of the α-iodonium ion is more favoured. The 1,2-
trans-α-rhamnoside 2i can only be formed via the α -iodonium
ion intermediate.
3. Conclusion
In conclusion, we have developed two new methods for
iodoacetoxylation and iodobenzoylation of protected glycals
using hypervalent iodine reagents i.e., BAIB/I2 and IBX/I2
respectively. The present methods avoids the expensive halide
sources (NIS, KI, etc.) and are also economically useful because
of minimum reagents loading (0.6 equiv of BAIB and 1.2 equiv
of I2) compared to previous reports, less reaction times, mild
reaction conditions. Here, we have also synthesized a chiral
building block 3,2-enolone 8 in a single step by using the method
A that could be used as a dienophile partner of Diels-Alder
reaction.35,36 We have also disclosed preparation of
diastereomerically enriched α-glycosyl ortho-hexynylbenzoate
12, a glycosyl donor in a two-step process from D-glucal 1a and
which was successfully utilized for glycosylation reaction to
obtain glycosides 13-15 in very good yields and with very high
α-selectivity (>99%).
4. Experimental Section
4.1. General
Scheme 4: Synthesis of ortho-hexynyl benzoates by Sonogashira coupling
and its glycosylation reaction. Reagents and conditions: (a) IBX, I2, dry
DCM, rt, 45 min, 74%; (b) n-hexyne, PdCl2(PPh3)2, CuI, iPr2NH, PPh3, rt,
85%; (c) ROH, PPh3AuNTf2, dry DCM, 4A° MS, -78 °C- rt.
The organic solvents were made anhydrous by standard methods
before their use. Silica gel (60F-254) 2.5 × 5 cm TLC plates
coated with a 0.25 mm thickness were used to monitor the
progress of the reaction. Visualization of the spots was done by
spraying the plate with Ce(SO4)2 (1% in 2N H2SO4) and
subsequent charring over hot plate. Silica gel (60–120 mesh) and
silica gel (230-400 mesh) were used for column chromatography.
All the intermediates were characterized by NMR, IR, ESI-
HRMS and the identifications of known compounds were done
by comparing their optical rotation with those reported in the
literature. NMR experiments were recorded in CDCl3 at 25 ºC.
Chemical shift values are given on δ scale with reference to TMS
at 0.00 ppm for proton and carbon. The reference CDCl3
appeared at 77.26 ppm for 13C NMR. NMR spectra were
recorded on Bruker Avance 400 MHz spectrometer at 400 MHz
(1H) and 100 MHz (13C).
A plausible mechanistic explanation is proposed based on our
results and other literature reports as well to understand course of
the reaction process, (Scheme 5).31-33 Molecular iodine readily
undergoes oxidation reaction with hypervalent iodine reagent
(BAIB or IBX) to generate two molecules of hypoiodite
(CH3COOI or O-IPhCOOI).31 This in situ generated I+ (from
IOOCR) forms two types of iodonium ions (π-complexes) i.e., α
and β 1,2-iodonium ions similar to the 1,2-episilinoniumion with
electron rich double bond of glycals.32 In contrast to 1,2-
epoxides33 of glycals, β -iodonium ion A is more stable than α -
iodonium ion C due to non-covalent interaction between spatially
closed β -iodonium ion and lone pair of electrons or non-bonded
electrons of ring oxygen. In this situation, the nucleophilic ligand
(R'COO-) attacks iodonium ion in concerted manner (SN2) to give
corresponding diaxial product B in a major amount.33
D-arabinal
(1g or 1h) also followed the same mechanistic path but finally
delivered the corresponding product in 1C4 conformation as
34
discussed above.16b,
However, in the case of L-rhamnal, it
Scheme 5: Plausible mechanism for synthesis of major products 2 and 11a.
5

Optical rotations were determined on HORIBA, high sensitive
(2R,3S,4S,5S,6R)-6-(acetoxymethyl)-3-iodotetrahydro-2H-
pyran-2,4,5-triyl triacetate 2c: This compound was synthesized
by adopting the general procedure I using tri-O-acetyl-D-galactal
ACCEPTED MANUSCRIPT
polarimeter, SEPA-300 using a 1 dm cell at 17 ºC-32 ºC in
chloroform; concentrations mentioned are in g/100 mL. For IR
spectra were recorded on Perkin–Elmer 881 and FTIR-8210 PC
Shimadzu Spectrophotometers. Mass spectra were recorded on a
JEOL JMS-600H high resolution spectrometer using EI mode at
70 eV. ESI-HRMS were recorded on a JEOL-AccuTOF, JMS-
T100LC spectrometer.
1c (100 mg, 0.368 mmol) as the starting material. Yield: (162
mg, 0.352 mmol, 96%, α:β: 92:8).
α-manno isomer: [α]D22= +42.0 (c 0.1, CHCl3); Rf: 0.42 (1:5,
EtOAc/Hexane); IR (Neat): νmax 3010, 2920, 2756, 1722, 1655,
1362, 1253, 1120, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
6.44 (d, J=1.04 Hz, 1H), 5.36-5.37 (m, 1H), 4.82-4.84 (m, 1H),
4.34 (td, J1=2.01, J2=6.64 Hz, 1H), 4.21-4.22 (m, 1H), 4.11-4.13
(I). General procedure for the synthesis of 2-deoxy-2-
iodoglycosylacetates: To a stirred solution of glycal in dry DCM
(5 mL), were added BAIB (0.6 equiv.), and iodine (1.2 equiv.) at
room temperature and allow the stirring for 30 min. After
consumption of the starting material observed by TLC, the
reaction mixture was quenched with saturated solution of sodium
thiosulfate (Na2S2O3.5H2O). The two layers were separated and
aqueous layer was extracted 2-3 times with DCM. The combined
organic layers were dried over sodium sulphate and the solvent
was evaporated in vacuum. The crude was subjected to column
chromatography to obtain the pure compound.
(m, 2H), 2.12 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H); 13
C
(100 MHz, CDCl3): δ 170.68, 170.22, 169.80, 168.43, 96.26,
69.30, 65.09, 65.05, 61.71, 29.90, 21.16, 21.06, 20.88, 19.14;
+
ESI-HRMS: m/z [M+Na]+ calcd for C14H19INaO9 480.9971,
measured 480.9960.
(2R,3S,4S,5S,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-
iodotetrahydro-2H-pyran-2-yl acetate 2d: This compound was
prepared by using the above mentioned general procedure I using
tri-O-benzyl-D-galactal 1d (250 mg, 0.601 mmol) as the starting
material. Yield: (351 mg, 0.583 mmol, 97%, α:β: 90:10).
α-manno isomer: [α]D22= +53.2 (c 0.1, CHCl3); Rf: 0.32 (1:9,
EtOAc/Hexane); IR (Neat): νmax,3017, 2926, 1725, 1635, 1418,
Compound 2a and 3a: These compound were synthesized by
adopting the general procedure I using tri-O-acetyl-D-glucal 1a
1
1207, 1109, 752, 665 cm-1; H (400 MHz, CDCl3): δ 7.19-7.33
(100 mg, 0.368 mmol) as the starting material. Yield: 0.341
(m, 14H), 7.09-7.11 (m, 2H), 6.33 (d, J=1.6 Hz, 1H), 4.79 (d,
J=10.6 Hz, 1H), 4.63 (d, J=11.8 Hz, 2H), 4.38-4.47 (m, 3H),
4.36-4.38 (m, 1H), 3.90-3.92 (m, 2H), 3.69-3.70 (m, 1H), 3.62-
3.69 (m, 1H), 3.15-3.36 (m, 1H), 1.95 (s, 3H); 13C (100 MHz,
CDCl3): δ 168.77, 138.48, 138.22, 137.55, 128.72, 128.62,
128.55, 128.35, 128.33, 128.25, 128.05, 127.96, 127.77, 95.76,
76.42, 75.64, 75.63, 75.07, 73.77, 71.31, 68.82, 31.24, 21.06;
mmol, 93% overall yield (α:β: 148:9 mg, dr 95:5).
2a (α-manno diastereomer): [α]D22= +31.5 (c 0.1, CHCl3); Rf:
0.42 (1:5, EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856,
1
1722, 1656, 1462, 1253, 1122, 1063, 755, 665 cm-1; H (400
MHz, CDCl3): δ 6.37 (d, J=1.16 Hz, 1H), 5.43 (t, J=9.72 Hz,
1H), 4.57 (dd, J1=4.38, J2=9.39 Hz, 1H), 4.51 (dd, J1=1.52,
J2=4.38 Hz, 1H), 4.21 (dd, J1=4.47, J2=12.25 Hz, 1H), 4.08-4.12
+
ESI-HRMS: m/z [M+Na]+ calcd for C29H31INaO6 625.1063,
(m, 2H), 2.14 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H); 13
C
measured 625.1059.
(100 MHz, CDCl3): δ 170.80, 170.04, 169.43, 168.29, 94.86,
71.59, 68.79, 67.20, 62.00, 27.32, 21.04, 20.98, 20.86, 20.76.
(2R,3S,4S,5R,6R)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-3-
iodo-4,5-bis(methoxymethoxy)tetrahydro-2H-pyran-2-yl
acetate 2e: This compound was prepared by using the above
+
ESI-HRMS: m/z [M+H]+ calcd for C14H20IO9 459.0152,
measured 459.0144.
3a (β-gluco diastereomer): [α]D22= +61.8 (c 0.2, CHCl3); Rf: 0.50
(1:5, EtOAc/Hexane); IR (Neat): νmax 3018, 2931, 2858, 1702,
mentioned general procedure
I
using (((2R,3S,4R)-3,4-
bis(methoxymethoxy)-3,4-dihydro-2H-pyran-2-yl)methoxy)(tert-
butyl)diphenylsilane (glucal derived) 1e (200 mg, 0.424 mmol)
as the starting material. Yield: (250 mg, 0.381 mmol, 90%, α:β:
85:15).
1
1584, 1427, 1253, 1122, cm-1; H (400 MHz, CDCl3): δ 5.80 (d,
J=9.69 Hz, 1H), 5.27 (dd, J1=9.07, J2=11.08 Hz, 1H), 4.94 (dd,
J1=9.26, J2=10.1 Hz, 1H), 4.25 (dd, J1=4.53, J2=12.53 Hz, 1H),
4.03 (dd, J1=2.09, J2=12.53 Hz, 1H), 3.92 (dd, J1=9.57, J2=11.14
Hz, 1H), 3.79-3.83 (m, 1H), 2.10 (s, 3H), 2.03 (s, 3H), 2.01 (s,
3H), 1.95 (s, 3H); 13C (100 MHz, CDCl3): δ 170.77, 169.73,
169.72, 168.76, 94.22, 75.79, 73.26, 68.77, 61.73, 29.93, 25.94,
α-manno isomer: [α]D22= -47.5 (c 0.2, CHCl3); Rf: 0.50 (1:4,
EtOAc/Hexane); IR (Neat): νmax 3009, 2925, 2846, 1723, 1656,
1460, 1253, 1130, 1063, 750, 660 cm-1; 1H (400 MHz, CDCl3): δ
7.56-7.58 (m, 4H), 7.28-7.35 (m, 6H), 6.42 (bs, 1H), 4.82-4.84
(m, 1H), 4.73-4.75 (m, 1H), 4.59-4.63 (m, 2H), 3.83-3.91 (m,
2H), 3.75-3.77 (m, 2H), 3.73-3.74 (m, 1H) 3.49-3.51 (m, 1H),
3.38 (s, 3H), 3.28 (s, 3H), 1.97 (s, 3H), 0.98 (s, 9H); 13C (100
MHz, CDCl3): δ 168.53, 135.80, 135.76, 133.56, 133.46, 130.02,
127.94, 97.12, 96.71, 94.89, 74.10, 70.22, 70.07, 62.50, 56.70,
+
20.91, 20.78. ESI-HRMS: m/z [M+H]+ calcd for C14H20IO9
459.0152, measured 459.0144.
(2R,3S,4S,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-
iodotetrahydro-2H-pyran-2-yl acetate 2b: This compound was
prepared by following the above mentioned general procedure I
56.46, 29.90, 27.06, 22.88, 21.07, 19.40; ESI-HRMS: m/z
+
using tri-O-benzyl-D-glucal 1b (200 mg, 0.481 mmol) as the
[M+Na]+ calcd for C28H39INaO8Si
681.1330.
681.1357, measured
starting material. Yield: (274 mg, 0.456 mmol, 95%, α:β: 90:10).
22
α-manno: [α]D
= +7.6 (c 0.2, CHCl3); Rf: 0.32 (1:9,
(2R,3S,4S,5S,6R)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-3-
iodo-4,5-bis(methoxymethoxy)tetrahydro-2H-pyran-2-yl
acetate 2f: This compound was prepared by using the above
EtOAc/Hexane); IR (Neat): νmax 3019, 2931, 1720, 1638, 1428,
1
1109, 669 cm-1; H (400 MHz, CDCl3): δ 7.18-7.33 (m, 13 H),
7.10-7.12 (m, 2H), 6.33 (s, 1H), 4.79 (d, J=10.55 Hz, 1H), 4.63
(d, J=11.77 Hz, 2H), 4.44-4.48 (m, 3H), 4.37-4.38 (m, 1H), 3.86-
3.95 (m, 2H), 3.69-3.73 (m, 1H), 3.59-3.62 (m, 1H), 3.13-3.16
(m, 1H) 1.96 (s, 3H). 13C (100 MHz, CDCl3): δ 168.78, 138.48,
138.22, 137.55, 128.72, 128.63, 128.56, 128.35, 128.26, 128.05,
127.97, 127.78, 95.76, 76.42, 75.64, 75.07, 73.77, 71.31, 68.81,
mentioned general procedure
I
using (((2R,3S,4R)-3,4-
bis(methoxymethoxy)-3,4-dihydro-2H-pyran-2-yl)methoxy)(tert-
butyl)diphenylsilane (galactal derived) 1f (300 mg, 0.635 mmol)
as the starting material. Yield: (364 mg, 0.553 mmol, 87%, α:β:
89:11).
+
31.24, 21.07; ESI-HRMS: m/z [M+Na]+ calcd for C29H31INaO6
α-manno isomer: [α]D22= -75.5 (c 0.38, CHCl3); Rf: 0.50 (1:4,
EtOAc/Hexane); IR (Neat): νmax 3117, 2986, 1721, 1630, 1415,
625.1063, measured 625.1045.
1
1205, 1120, 750, 660 cm-1; H (400 MHz, CDCl3): δ 7.56-7.58
(m, 4H), 7.28-7.35 (m, 6H), 6.42 (bs, 1H), 4.82-4.84 (m, 1H),
6

4.67-4.77 (m, 2H), 4.60-4.63 (m, 1H), 4.08-4.10 (m, 1H), 4.14-
J=8.56 Hz, 1H), 5.60 (t, J=2.76 Hz, 1H), 5.12-5.16 (m, 1H),
4.22-4.26 (m, 1H), 3.96-4.0 (m, 1H), 3.85-3.89 (m, 1H), 2.16 (s,
6H), 2.06 (s, 3H); 13C (100 MHz, CDCl3): δ 170.21, 169.62,
168.86, 94.95, 73.44, 67.80, 65.66, 25.37, 21.03, 20.93, 20.83;
ACCEPTED MANUSCRIPT
4.15 (m, 1H), 3.83-3.91 (m, 2H), 3.73-3.77 (m, 1H), 3.49-3.51
(m, 1H), 3.38 (s, 3H), 3.28 (s, 3H), 1.98 (s, 3H), 0.98 (s, 9H); 13
C
(100 MHz, CDCl3): δ 168.55, 137.78, 135.82, 133.59, 133.49,
130.04, 128.15, 127.96, 97.15, 96.74, 94.91, 74.12, 70.24, 70.09,
62.52, 56.72, 56.48, 27.07, 22.89, 21.09, 19.42; ESI-HRMS: m/z
[M+Na]+ calcd for C28H39INaO8 Si+ 681.1357, measured
681.1350.
ESI-HRMS: m/z [M+H]+ calcd for C11H16IO7 386.9941,
+
measured 386.9935.
(2R,3S,4R,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-
iodotetrahydrofuran-2-yl acetate 2k: This compound was
prepared by following the above mentioned general procedure I
(2R,4R,5R)-3-iodotetrahydro-2H-pyran-2,4,5-triyl triacetate
2g: This compound was prepared by following the above
using
(2R,3S)-3-(benzyloxy)-2-((benzyloxy)methyl)-2,3-
mentioned general procedure I using 3,4-di-O-acetyl-
D-arabinal
dihydrofuran 1k (200 mg, 0.676 mmol) as the starting material.
1g (100 mg, 0.5 mmol) as the starting material. Yield: (185 mg,
Yield: (318 mg, 0.661 mmol, 98%, α:β: 80:20).
α-manno isomer: [α]D = +5.43 (c 0.81, CHCl3); Rf: 0.23 (1:9,
22
0.48 mmol, 96%, α:β: 88:12); %).
22
α-manno isomer: [α]D = +73.7 (c 0.2, CHCl3); Rf: 0.50 (1:4,
EtOAc/Hexane); IR (Neat): νmax 3125, 3018, 2925, 1715, 1605,
1
EtOAc/Hexane); IR (Neat): νmax 3016, 2937, 1717, 1540, 1215,
1453, 1216, 1073, 769, 668 cm-1; H (400 MHz, CDCl3): δ 7.38-
1
1205, 1120, 1025 cm-1; H (400 MHz, CDCl3): δ 5.94 (d, J=8.49
7.39 (M, 2H), 7.22-7.29 (m, 8H), 5.89 (d, J=9.25 Hz, 1H), 4.86-
4.89 (m, 1H), 4.70-4.72 (m, 1H), 4.50-4.58 (m, 2H), 4.08 (bs,
1H), 3.96-4.01 (m, 2H), 3.83-3.87 (m, 1H), 3.68-3.72 (m, 1H),
2.02 (s, 3H); 13C (100 MHz, CDCl3): δ 169.17, 138.25, 137.87,
128.81, 128.44, 128.25, 127.92, 127.74, 93.00, 78.30, 75.59,
75.47, 72.08, 63.65, 29.03, 21.02. ESI-HRMS: m/z [M+Na]+
calcd for C21H23INaO5+ 505.0488, measured 505.0481.
Hz, 1H), 5.50 (t, J=2.58 Hz, 1H), 5.08-5.12 (m, 1H), 5.03-5.06
(m, 1H), 4.16 (dd, J1=3.10, J2=8.51Hz, 1H), 3.91-3.94 (m, 1H),
2.13 (s, 3H), 2.07 (s, 3H), 1.95 (s, 3H); 13C (100 MHz, CDCl3): δ
169.83, 169.71, 169.11, 93.12, 70.12, 66.33, 62.96, 24.23, 21.03,
+
20.93, 20.83; ESI-HRMS: m/z [M+Na]+ calcd for C11H15INaO7
408.9760, measured 408.9741.
(2R,3S,4R,5R)-4,5-bis(benzyloxy)-3-iodotetrahydro-2H-
pyran-2-yl acetate 2h: This compound was prepared by
adopting the above mentioned general procedure I using (3R,4R)-
3,4-bis(benzyloxy)-3,4-dihydro-2H-pyran 1h (150 mg, 0.507
mmol) as the starting material. Yield: (220 mg, 0.456 mmol,
90%, α:β: 86:14).
(2R,4S,5R,6R)-6-(acetoxymethyl)-3,3-diiodotetrahydro-2H-
pyran-2,4,5-triyl triacetate 2l: This compound was prepared by
using the above mentioned general procedure I using (2R,3R,4S)-
2-(acetoxymethyl)-5-iodo-3,4-dihydro-2H-pyran-3,4-diyl
diacetate 1l (200 mg, 0.503 mmol) as the starting material. Yield:
(278 mg, 0.477 mmol, 95%, α:β: 96:4).
α-manno isomer: [α]D22= +36.9 (c 0.18, CHCl3); Rf: 0.23 (1:2,
EtOAc/Hexane); IR (Neat): νmax 3239, 2930, 2399, 1732, 1638,
α-manno isomer: [α]D22 = -8.62 (c 0.32, CHCl3); Rf: 0.23 (1:3.5,
EtOAc/Hexane); IR (Neat): νmax 3055, 2830, 2156, 1722, 1650,
1253, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ 6.55 (s, 1H),
5.26 (t, J=9.49 Hz, 1H), 4.90 (d, J=8.95 Hz, 1H), 4.03-4.15 (m,
3H), 2.15 (s,3H), 2.15 (s, 3H), 2.02 (s, 3H), 1.97 (s, 3H); 13C (100
MHz, CDCl3): δ 170.76, 169.83, 169.43, 168.03, 96.22, 75.81,
71.12, 68.71, 61.70, 21.11, 20.91, 20.80, 20.72, 0.90; ESI-
1
1403, 1215, 1063, 669 cm-1; H (400 MHz, CDCl3): δ 7.18-7.35
(m, 10 H), 5.72 (d, J=8.35, 1H), 4.48-4.65 (m, 4H), 4.33 (dd,
J1=8.37, J2=10.03 Hz, 1H), 4.07 (dd, J1=3.23, J2=12.75 Hz, 1H),
3.62-3.64 (m, 1H), 3.56 (dd, J1=3.13, J2=10Hz, 1H), 3.44 (dd,
J1=1.36, J2=12.71 Hz, 1H), 2.06 (s, 3H); 13C (100 MHz, CDCl3):
δ 169.44, 137.93, 137.41, 128.71, 128.38, 128.30, 128.23,
128.15, 95.44, 81.15, 72.46, 71.70, 71.59, 64.55, 29.47, 21.05;
+
HRMS: m/z [M+Na]+ calcd for C14H18I2NaO9 606.8938,
measured 606.8905.
+
ESI-HRMS: m/z [M+Na]+ calcd for C21H23INaO5 505.0488,
measured 505.0472.
Methyl (E)-3-((2R,3S,4S,5R,6R)-2-acetoxy-4,5-bis(benzyloxy)-
6-((benzyloxy)methyl)-3-iodotetrahydro-2H-pyran-3-
(2S,3R,4R,5S,6S)-3-iodo-6-methyltetrahydro-2H-pyran-2,4,5-
triyl triacetate 2i: This compound was prepared by adopting the
yl)acrylate 2n: This compound was prepared by adopting the
above mentioned general procedure I using (E)-methyl 3-
((2R,3S,4R)-3,4-bis(benzyloxy)-2-((benzyloxy)methyl)-3,4-
dihydro-2H-pyran-5-yl)acrylate 1n (100 mg, 0.20 mmol) as the
starting material. Yield: (103 mg, 0.150 mmol, 75%, α:β: 80:20).
above mentioned general procedure
I using (3R,4R)-3,4-
bis(benzyloxy)-3,4-dihydro-2H-pyran 1i (100 mg, 0.467 mmol)
as the starting material. Yield: (168 mg, 0.42 mmol, 90%, α:β:
80:20).
22
α-manno isomer: [α]D = -37.0 (c 0.21, CHCl3); Rf: 0.40 (1:9,
22
α-manno isomer: [α]D = +25.3 (c 1.0, CHCl3); Rf: 0.23 (1:3.5,
EtOAc/Hexane); IR (Neat): νmax 3010, 2940, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
7.10-7.41 (m, 15H), 6.49-6.53 (d, J=16.27 Hz, 1H), 6.32 (s, 1H),
5.98 (s, 1H), 4.67-4.76 (m, 2H), 4.55-4.58 (m, 1H), 4.39-4.47 (m,
3H), 4.09-4.14 (m, 1H), 3.93-3.95 (m, 1H), 3.66-3.75 (m, 5H),
3.58-3.61 (m, 1H), 2.09 (s, 3H); 13C (100 MHz, CDCl3): δ
168.62, 166.53, 142.27, 138.22, 137.83, 133.42, 130.63, 128.84,
128.80, 128.64, 128.36, 128.22, 128.07, 127.94, 127.89, 127.39,
126.60, 106.27, 91.28, 81.23, 80.11, 75.27, 75.09, 73.80, 72.51,
68.19, 52.08, 29.94, 21.14; ESI-HRMS: m/z [M+Na]+ calcd for
C33H35INaO8 + 709.1274, measured 709.1264.
EtOAc/Hexane); IR (Neat): νmax 3110, 2942, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
6.27 (s, 1H), 5.10-5.15 (m, 1H), 4.44-4.47 (m, 2H), 3.92-3.99 (m,
1H), 2.08 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 1.18 (d, J=6.25 Hz,
3H); 13C (100 MHz, CDCl3): δ 170.24, 169.82, 168.67, 95.07,
72.31, 69.76, 69.03, 28.23, 21.20, 21.12, 20.96, 17.83; ESI-
HRMS: m/z [M+Na]+ calcd for C8H13INaO2+ 422.9917, measured
422.9905.
(2R,3S,4R,5R)-5-(acetoxymethyl)-3-iodotetrahydrofuran-2,4-
diyl diacetate 2j: This compound was prepared by using the
above mentioned general procedure I using ((2R,3S)-3-acetoxy-
2,3-dihydrofuran-2-yl)methyl acetate 1j (200 mg, 1mmol) as the
starting material. Yield: (366 mg, 0.95mmol, 95%, α:β: 90:10).
(2R,3S,4S,5R,6R)-6-(acetoxymethyl)-3-((E)-2-cyanovinyl)-3-
iodotetrahydro-2H-pyran-2,4,5-triyl triacetate 2o: This
compound was prepared by using the above mentioned general
22
procedure
I
using (2R,3S,4R)-2-(acetoxymethyl)-5-((E)-2-
α-manno isomer: [α]D = -20.3 (c 0.2, CHCl3); Rf: 0.5 (1:3,
cyanovinyl)-3,4-dihydro-2H-pyran-3,4-diyl diacetate 1o (200
EtOAc/Hexane); IR (Neat): νmax 3018, 2931, 1742, 1684, 1471,
1216, 1032, 750, 660 cm-1; 1H (400 MHz, CDCl3): δ 6.02 (d,
7

mg, 0.619 mmol) as the starting material. Yield: (268 mg, 0.526
1746, 1521, 668 cm-1; ESI-HRMS: m/z [M+H]+ calcd for
ACCEPTED MANUSCRIPT
C14H17F3IO9+ 512.9869, measured 512.9853.
mmol, 85%, α:β: 85:15).
22
α-manno isomer: [α]D = -26.0 (c 0.18, CHCl3); Rf: 0.23 (1:2,
(II) General procedure for the synthesis of 2-deoxy-2-
iodoglycosyl ortho-iodobenzoates: To a stirred solution of
glycal in dry DCM (5 mL), were added IBX (1.5 equiv.) and
iodine (1.2 equiv.) in equivalent amounts at room temperature
and allow the stirring for 30 to 45 min. After consumption of the
starting material (monitored by TLC), the reaction mixture was
quenched with saturated solution of Na2S2O35H2O. The two
layers were separated and aqueous layer was extracted 2-3 times
with DCM. The combined organic layers were dried over sodium
sulphate and the solvent was evaporated in vacuum. The crude
was subjected to column chromatography to obtain pure
compound.
EtOAc/Hexane); IR (Neat): νmax 3125, 3018, 2925, 1715, 1605,
1
1453, 1216, 1073, 769, 668 cm-1; H (400 MHz, CDCl3): δ 6.73
(d, J=17.06 Hz, 1H), 5.98-6.02 (m, 2H), 5.46 (d, J=9.88 Hz ,
1H), 4.98 (t, J=.9.60 Hz, 1H), 4.04-4.16 (m, 2H), 3.84-3.88 (m,
1H), 2.16 (s, 3H), 2.10 (s, 3H), 2.01 (s, 3H), 1.95 (s, 3H); 13C
(100 MHz, CDCl3): δ 170.65, 169.46, 169.02, 168.14, 147.83,
116.53, 105.49, 95.93, 77.99, 74.33, 66.22, 61.38, 43.11, 20.88,
20.67; ESI-HRMS: m/z [M+Na]+ calcd for C17H20INNaO9
+
532.0080, measured 532.0075.
3-iodotetrahydro-2H-pyran-2-yl acetate 2p: This compound
was prepared by using the above mentioned general procedure I
using 3,4-dihydro-2H-pyran 1p (200 mg, 2.38 mmol) as the
starting material. Yield: (624 mg, 2.31 mmol, 97%); Rf: 0.50
(Pure Hexane); IR (Neat): νmax 3427, 3015, 2930, 1641, 1427,
(2R,3R,4S,5S,6R)-2-(acetoxymethyl)-5-iodo-6-((2-
iodobenzoyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate 11a:
This compound was prepared by using the above mentioned
1
1217, 1106, 919, 764 cm-1; H (400 MHz, CDCl3): δ 5.82 (d,
general procedure II using tri-O-acetyl-D-glucal 1a (100 mg,
0.3676 mmol) as the starting material. Yield: (176 mg, 0.272
J=5.80 Hz, 1H), 5.24 (s, 1H), 4.04-4.09 (m, 1H), 3.94-3.99 (m,
1H), 3.65-3.71 (m, 1H), 2.28-2.36 (m, 1H), 2.01-2.04 (m, 4H),
1.74-1.78 (m, 1H), 1.56-1.61 (m, 1H); 13C (100 MHz, CDCl3): δ
169.20, 95.61, 65.17, 32.68, 26.40, 25.40, 21.08. ESI-HRMS: m/z
[M+Na]+ calcd for C7H11INaO3+ 292.9651, measured 292.9645.
mmol, 74%, α:β: 98:2).
α-manno isomer: [α]D = +25 (c 0.5, CHCl3); Rf: 0.23 (1:3.5,
22
EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
7.96 (dd, J1=1, J2=7.97 Hz, 1H), 7.76 (dd, J1=1.69, J2=7.80 Hz,
1H), 7.39 (td, J1=1.16, J2=7.55 Hz, 1H), 7.15 (td, J1=1.52,
J2=7.74 Hz, 1H), 6.59 (s, 1H), 5.43-5.48 (m, 1H), 4.67-4.71 (m,
1H), 4.13-4.22 (m, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.00 (s, 3H);
13C (100 MHz, CDCl3): δ 170.92, 170.09, 169.57, 164.16,
141.87, 134.21, 133.67, 131.82, 128.41, 96.34, 94.18, 72.27,
69.10, 67.25, 62.07, 27.24, 21.14, 20.99, 20.87; ESI-HRMS: m/z
[M+Na]+ calcd for C19H20I2NaO9+ 668.9094, measured 668.9085.
2-iodocyclohexyl acetate 2q: This compound was prepared by
using the above mentioned general procedure
I using
cyclohexene 1q (200 mg, 2.43 mmol) as the starting material.
Yield: (595 mg, 2.22 mmol, 91%); Rf: 0.50 (20:1,
EtOAc/Hexane); IR (Neat): νmax 3427, 3015, 2930, 1641, 1427,
1
1217, 1106, 919, 764 cm-1; H (400 MHz, CDCl3): δ 4.80-4.86
(m, 1H), 3.96-4.02 (m, 1H), 2.34-2.41 (m, 1H), 1.91-2.07 (m,
5H), 1.73-1.76 (m, 1H), 1.48-1.55 (m, 1H), 1.19-1.42 (m, 3H);
13C (100 MHz, CDCl3): δ 170.16, 76.95, 38.12, 31.98, 31.84,
27.31, 23.82, 21.45; ESI-HRMS: m/z [M+Na]+ calcd for
C8H13INaO2+ 290.9858, measured 290.9838.
(2R,3S,4S,5R,6R)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-3-
iodotetrahydro-2H-pyran-2-yl 2-iodobenzoate 11b: This
compound was prepared by using the above mentioned general
1,3,6-Tri-O-acetyl-4-deoxy-u-~glycero-hex-3-enopyranos-2-
ulose (Compound 8): This compound was prepared by using the
procedure II using tri-O-benzyl-D-glucal 1b (150 mg, 0.360
mmol) as the starting material. Yield: (224 mg, 0.283 mmol,
above mentioned general procedure I using 2-acetoxy-D-glucal 5
79%, α:β: 98:2).
α-manno isomer: [α]D = +36 (c 1.0, CHCl3); Rf: 0.23 (1:3.5,
22
(100 mg, 0.3027 mmol) as the starting material. The crude
mixture was subjected to flash column chromatography. In the
column the intermediate 6 was converted into 7. Yield: (62 mg,
EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
7.89 (dd, J1=0.96, J2=7.93 Hz,1H), 7.59 (dd, J1=1.60, J2=7.81
Hz, 1H), 7.20-7.36 (m, 15H), 7.06-7.13 (m, 3H), 6.61 (d, J=1.23
Hz, 1H), 4.81-4.84 (m, 1H), 4.64-4.69 (m, 2H), 4.57-4.59 (m,
1H), 4.44-4.54 (m, 2H), 3.96-4.02 (m, 2H), 3.72-3.77 (m, 2H),
3.62-3.65 (m, 1H), 3.29-3.32 (m, 1H); 13C (100 MHz, CDCl3): δ
164.36, 141.69, 138.50, 138.23, 137.61, 134.32, 133.41, 131.64,
128.78, 128.63, 128.56, 128.41, 128.32, 128.26, 127.97, 127.77,
97.20, 94.21, 76.24, 75.74, 75.73, 75.63, 73.80, 71.26, 68.78,
22
0.216 mmol, 72%)19c; [α]D = +32.4 (c 0.3, CHCl3); Rf: 0.40
(1:9, EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722,
1
1656, 1462, 1253, 1122, 1063, 755, 665 cm-1; H (400 MHz,
CDCl3): δ 6.62 (d, J=1.93 Hz, 1H), 6.23 (s, 1H), 4.95 (dt,
J1=1.88, J2=4.86 Hz, 1H), 4.39 (dd, J1=5.11, J2=11.73 Hz, 1H),
4.14 (dd, J1=4.73, J2=11.73 Hz, 1H), 2.20 (s, 3H), 2.08 (s, 3H),
2.03 (s, 3H); 13C (100 MHz, CDCl3): δ 181.32, 170.85, 168.94,
168.00, 142.27, 133.20, 90.27, 69.23, 64.46, 20.97, 20.90, 20.52;
+
ESI-HRMS: m/z [M+H]+ calcd for C12H15O8
287.0767,
31.16; ESI-HRMS: m/z [M+NH4]+ calcd for C34H36I2NO6
813.0632, measured 808.0651.
+
measured 287.0753.
Compound 9 and 10: Bis[(trifluoroacetoxy)iodo] benzene (94
mg, 0.218 mmol) and I2 (102 mg, 0.4 mmol) were added to the
stirred solution of tri-O-acetoxy-D-glucal (100 mg, 0.3676) in dry
(2R,3S,4S,5S,6R)-2-(acetoxymethyl)-5-iodo-6-((2-
iodobenzoyl)oxy)tetrahydro-2H-pyran-3,4-diyl diacetate 11c:
This compound was prepared by using the above mentioned
DCM (5 mL) at rt and continues the stirring at the same
temperature for 30 min Then the reaction was quenched with the
saturated solution of Na2S2O35H2O (5 mL) and the two layers
were separated. The aqueous layer was extracted with DCM
(2X5 mL) and combined organic layers were dried over sodium
sulphate and concentrated in vacuum to obtain a residue. Its silica
gel column chromatography led to give an inseparable mixture of
9 and 10 (α:β: 90:10) in 85% yield (159 mg, 0.312 mmol); Rf:
0.45 (1:2, EtOAc/Hexane); IR (Neat): νmax 3020, 2959, 2400,
general procedure II using tri-O-acetyl-D-galactal 1c (100 mg,
0.3676 mmol) as the starting material. Yield: (173 mg, 0.268
mmol, 73%, α:β: 98:2).
22
α-manno isomer: [α]D = -24.8 (c 1.0, CHCl3); Rf: 0.23 (1:3.5,
EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
7.95 (d, J=7.85 Hz, 1H), 7.74 (d, J=7.85 Hz, 1H), 7.39 (t, J=7.48
Hz, 1H), 7.15 (t, J=7.48 Hz, 1H), 6.72 (s, 1H), 5.42 (bs, 1H),
4.99-5.00 (m, 1H), 4.49-4.52 (m, 1H), 4.42-4.43 (m, 1H), 4.10-
8

13C (100
deoxy-2-iodo-(2-iodobenzyloxy) glycosylacetate 11a (500 mg,
0.773 mmol) in dry iPr2NH (1.5 mL) and then degassed the
4.16 (m, 2H), 2.15 (s, 3H), 2.02 (s, 3H), 1.96A(sC, 3CHE); PTED MANUSCRIPT
MHz, CDCl3): δ 170.58, 170.17, 169.68, 164.09, 141.79, 134.17,
133.63, 131.77, 128.38, 97.83, 94.06, 69.92, 65.09, 65.02, 61.74,
21.15, 21.03, 20.88, 18.77; ESI-HRMS: m/z [M+Na]+ calcd for
C19H20I2NaO9+ 668.9094, measured 668.9091.
resulting solution. After stirring at rt for 1 h under a nitrogen
atmosphere, 1-hexyne (0.132 mL, 1.16 mmol) was slowly added
at 0°C. The mixture was allowed to stir at rt for 18 h and
saturated NH4Cl was added. After vigorously stirring for 30 min
petroleum ether (10 mL) was added and the two phases were
separated. The aqueous layer was extracted with EtOAc (10 mL),
the combined organic layers were washed with H2O and brine,
dried over Na2SO4, then concentrated. The crude product was
subjected to silica gel column chromatography (hexane/ EtOAc
90:10) to provide pure glycosyl 2-hex-1-ynyl benzoate 12 in 85%
(2R,3S,4S,5S,6R)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-3-
iodo-4,5-bis(methoxymethoxy)tetrahydro-2H-pyran-2-yl
2-
iodobenzoate 11d: This compound was prepared by using the
above mentioned general procedure II using (((2R,3S,4R)-3,4-
bis(methoxymethoxy)-3,4-dihydro-2H-pyran-2-yl)methoxy)(tert-
butyl)diphenylsilane 1f (200 mg, 0.422 mmol) as the starting
material. Yield: (246 mg, 0.291 mmol, 69%, α:β: 90:10).
22
(394 mg, 0.66 mmol); [α]D = +73.2 (c 0.2, CHCl3); Rf: 0.23
22
(1:5, EtOAc/Hexane); IR (Neat): νmax 3022, 2929, 2402, 2250,
1749, 1584, 1427, 1068, 761, 670 cm-1; 1H (400 MHz, CDCl3): δ
7.93-7.95 (m, 1H), 7.47-7.50 (m, 1H), 7.39-7.43 (m, 1H), 7.28
(dd, J1=7.61, J2=15.46 Hz, 1H), 6.05 (d, J=9.39 Hz, 1H), 5.31-
5.36 (m, 1H), 4.98-5.02 (m, 1H), 4.04-4.08 (m, 3H), 3.88-3.92
(m, 1H), 2.43 (t, J=7.19 Hz, 2H), 2.05 (s, 3H), 2.00 (s, 3H), 1.97
(s, 3H), 1.53-1.61 (m, 2H), 1.38-1.49 (m, 2H), 0.89 (t, J=7.23 Hz,
3H). 13C (100 MHz, CDCl3): δ 171.34, 170.78, 169.75, 163.40,
134.91, 132.76, 131.07, 129.64, 127.36, 126.07, 97.52, 94.68,
79.26, 75.63, 73.25, 68.82, 61.77, 30.90, 25.86, 22.31, 21.25,
20.94, 20.80, 19.85, 13.89; ESI-HRMS: m/z [M+Na]+ calcd for
C25H29INaO9+ 623.0754, measured 623.0737.
α-manno isomer: [α]D = +15.2 (c 0.3, CHCl3); Rf: 0.23 (1:3.5,
EtOAc/Hexane); IR (Neat): νmax 3015, 2930, 2856, 1722, 1656,
1462, 1253, 1122, 1063, 755, 665 cm-1; 1H (400 MHz, CDCl3): δ
7.95 (d, J=8.04 Hz, 1H), 7.64 (dd, J1=1.66, J2=7.74 Hz, 1H),
7.52-7.56 (m, 4H), 7.21-7.39 (m, 7H), 7.14 (td, J1=1.78, J2=7.73
Hz, 1H), 6.71 (s, 1H), 4.86-4.88 (m, 1H), 4.75-4.77 (m, 1H),
4.61-4.71 (m, 2H), 4.38-4.40 (m, 1H), 4.16 (bs, 1H), 4.05-4.08
(m, 1H), 3.85-3.90 (m, 1H), 3.76-3.80 (m, 1H), 3.68-3.70 (m,
1H), 3.37 (s, 3H), 3.29 (s, 3H), 0.96 (s, 9H); 13C (100 MHz,
CDCl3): δ 164.51, 141.60, 135.78, 135.10, 133.48, 133.44,
133.31, 131.73, 130.04, 128.29, 128.16, 127.98, 127.95, 98.70,
97.25, 94.80, 93.90, 74.76, 70.18, 69.96, 62.65, 56.70, 56.53,
29.94, 27.11, 22.32; ESI-HRMS: m/z [M+Na]+ calcd for
C33H40I2NaO8Si+ 869.0480, measured 869.0470.
(III) General procedure for the glycosylation with glycosyl
ortho-hexenylbenzoates 12 as donors:
A
solution of
PPh3AuNTf2 in DCM was added at -78 °C to a mixture of ortho-
hexenylbenzoates 12 (0.218 mmol), acceptors and 4 Å MS in dry
DCM (5 mL). The mixture was allowed to stir at the same
temperature for 2-3 h. Then the reaction shifted to room
temperature and it was filtered through celite bed and the filterate
was concentrated. The residue was purified by silica gel column
chromatography to provide pure compounds.
(3R,4R,5S,6R)-5-iodo-6-((2-iodobenzoyl)oxy)tetrahydro-2H-
pyran-3,4-diyl diacetate 11e: This compound was prepared by
using the above mentioned general procedure II using (3R,4S)-
3,4-dihydro-2H-pyran-3,4-diyl diacetate 1g (100 mg, 0.5 mmol)
as the starting material. Yield: (186 mg, 0.324 mmol, 65%, α:β:
92:8).
α-manno isomer: [α]D22 = +155.3 (c 0.15, CHCl3); Rf: 0.23 (1:4,
EtOAc/Hexane); ); IR (Neat): νmax 3019, 2927, 2400, 1751, 1637,
1
1453, 1371, 1216, 1063, cm-1; H (400 MHz, CDCl3): δ 7.9 (d,
(2R,3R,4S,5S,6S)-2-(acetoxymethyl)-6-(benzyloxy)-5-
iodotetrahydro-2H-pyran-3,4-diyl
diacetate
13:
This
J=8.07 Hz, 1H), 7.88 (dd, J1=1.39, J2=7.72 Hz, 1H), 7.36-7.40
(m, 1H), 7.12-7.16 (m, 1H), 6.22 (d, J=8.06 Hz, 1H), 5.55-5.56
(m, 1H), 5.09-5.13 (m, 1H), 4.32-4.35 (m, 1H), 3.93-4.03 (m,
2H), 2.15 (s, 3H), 1.98 (s, 3H); 13C (100 MHz, CDCl3): δ 170.58,
169.68, 164.09, 141.79, 134.17, 133.63, 131.77, 128.38, 97.83,
94.06, 69.92, 65.02, 61.74, 21.15, 20.89, 18.77; ESI-HRMS: m/z
[M+Na]+ calcd for C16H16I2NaO7 596.8883, measured 596.8870.
compound was synthesized by above mentioned general
procedure III using benzyl alcohol (0.24 mmol) as an acceptor;
Yield: (96 mg, 0.189 mmol, 92%); Rf: 0.23 (1:3, EtOAc/Hexane);
22
[α]D = +40.3 (c 0.3, CHCl3); IR (Neat): νmax 3015, 2930, 2856,
1
1722, 1656, 1462, 1253, 1122, 1063, 755, 665 cm-1; H (400
MHz, CDCl3): δ 7.31-7.39 (m, 5H), 5.39 (t, J=9.33 Hz, 1H), 5.25
(s, 1H), 4.65-4.71 (m, 2H), 4.54-4.57 (m, 2H), 4.22 (dd, J1=4.77,
J2=12.20 Hz, 1H), 4.08(dd, J1=2.41, J2=12.19 Hz, 1H), 4.01-4.05
(m, 1H), 2.12 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H); 13C (100 MHz,
CDCl3): δ 170.91, 170.05, 169.70, 136.57, 128.84, 128.51,
128.42, 100.77, 70.26, 69.57, 69.34, 67.80, 62.40, 29.75, 21.17,
(2R,3S,4R,5R)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-
iodotetrahydrofuran-2-yl 2-iodobenzoate 11f : This compound
was prepared by using the above mentioned general procedure II
using
(2R,3S)-3-(benzyloxy)-2-((benzyloxy)methyl)-2,3-
+
20.99, 20.87; ESI-HRMS: m/z [M+Na]+ calcd for C19H23INaO8
dihydrofuran 1j (200 mg, 0.5 mmol) as the starting material.
529.0335, measured 529.0335.
Yield: (339 mg, 0.506 mmol, 75%, α:β: 93:7).
22
α-manno isomer: [α]D = +80.7 (c 0.2, CHCl3); Rf: 0.4 (1:9,
(2R,3R,4S,5S,6S)-2-(acetoxymethyl)-5-iodo-6-
(((2R,3R,4S,5R,6S)-3,4,5-tris(benzyloxy)-6-(4-
methoxyphenoxy)tetrahydro-2H-pyran-2-
EtOAc/Hexane); ); IR (Neat): νmax 3023, 2931, 2856, 1752, 1642,
1
1372, 1218, 1122, 1071, cm-1; H (400 MHz, CDCl3): δ 7.94 (d,
J=7.92 Hz, 1H), 7.90 (dd, J1=1.58 J2=7.82 Hz, 1H), 7.37 (d, 7.50
Hz, 1H), 7.22-7.31 (m, 10H), 7.06-7.10 (m, 1H), 6.01 (d, J=6.75,
1H), 4.61-4.62 (m, 1H), 4.48-4.59 (m, 4H), 4.16 (dd, J1=4.93,
J2=12.26 Hz, 1H), 3.83-3.84 (m, 1H), 3.74 (dd, J1=2.91, J2=8.47,
1H); 13C (100 MHz, CDCl3): δ 164.04, 142.02, 137.92, 137.46,
133.59, 132.84, 132.26, 102.69, 96.28, 81.79, 80.27, 72.69,
71.75, 71.30, 32.40; ESI-HRMS: m/z [M+Na]+ calcd for
C26H24I2NaO5+ 692.9611, measured 692.9600.
Synthesis of (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-((2-(hex-1-
yn-1-yl)benzoyl)oxy)-5-iodotetrahydro-2H-pyran-3,4-diyl
diacetate 12: [PdCl2(PPh3)2] (54 mg, 0.08 mmol), CuI (14 mg,
0.07 mmol), and PPh3 (20 mg, 0.08 mmol) were added to 2-
yl)methoxy)tetrahydro-2H-pyran-3,4-diyl diacetate 14: This
compound was synthesized by above mentioned general
procedure III using glucose derived alcohol (133 mg, 0.24 mmol)
as an acceptor; Yield: (145 mg, 0.175 mmol, 85%); Rf: 0.23 (1:3,
22
EtOAc/Hexane); [α]D = +29.4 (c 0.1, CHCl3); IR (Neat): νmax
3012, 2830, 1722, 1556, 1362, 1250, 1022, 1063, 755, 665 cm-1;
1H (400 MHz, CDCl3): δ 7.27-7.36 (m, 15H), 7.00 (d, J=9 Hz,
2H), 6.86 (d, J=9.34 Hz, 2H), 5.34 (t, J=9.47 Hz, 1H), 5.19 (s,
1H), 5.04-5.07 (m, 1H), 4.89-4.98 (m, 3H), 4.79-4.83 (m, 2H),
4.57-4.63 (m, 3H), 3.99-4.08 (m, 2H), 3.91-3.95 (m, 1H), 3.69-
3.77 (m, 8H), 3.59-3.63 (m, 1H), 3.46-3.51 (m, 1H), 2.09 (s, 3H),
9

1
2.07 (s, 3H), 1.92 (s, 3H); 13C (100 MHz, CDCl3): δ 170.88,
169.99, 169.72, 155.48, 151.59, 138.56, 138.42, 138.05, 128.76,
128.68, 128.45, 128.15, 128.05, 118.18, 115.02, 102.61, 101.69,
84.89, 82.24, 77.92, 76.03, 75.26, 74.27, 69.35, 69.26, 67.41,
62.11, 55.77, 29.53, 21.21, 20.98, 20.66; ESI-HRMS: m/z
[M+Na]+ calcd for C39H44INaO12+ 977.2221, measured 977.2190.
cm-1; H (400 MHz, CDCl3): δ 7.13-7.36 (m, 16H), 6.89 (d,
ACCEPTED MANUSCRIPT
J=8.89 Hz, 2H), 6.72 (d, J=9.13 Hz, 2H), 5.46-5.48 (m, 2H),
5.24-5.29 (m, 1H) 4.76-4.79 (m, 1H), 4.58-4.65 (m, 4H), 4.48-
4.51 (m, 1H), 4.38-4.41 (m, 2H), 4.19-4.22 (m, 1H), 3.88-4.12
(m, 6H), 3.78-3.81 (m, 1H), 3.68-3.74 (m, 4H), 3.59-3.62 (m,
1H), 2.02 (s, 3H), 1.98 (s, 3H), 1.95 (s, 3H);13C (100 MHz,
CDCl3): δ 170.83, 169.95, 169.65, 155.32, 150.33, 138.35,
138.09, 138.0, 128.78, 128.54, 128.05, 128.01, 127.84, 127.79,
118.03, 114.88, 103.47, 96.47, 79.47, 75.39, 75.10, 73.65, 72.74,
72.47, 69.75, 69.11, 69.02, 68.0, 62.57, 55.87, 29.93, 21.18,
(2R,3R,4S,5S,6S)-2-(acetoxymethyl)-6-((R)-2-((tert-
butoxycarbonyl)amino)-2-phenylethoxy)-5-iodotetrahydro-
2H-pyran-3,4-diyl diacetate 15: This compound was
synthesized by above mentioned general procedure III using
unnatural amino acid phenylglycine derived alcohol (57 mg, 0.24
mmol) as an acceptor; Yield: (118 mg, 0.186 mmol, 87%); Rf:
20.92, 20.91; ESI-HRMS: m/z [M+Na]+ calcd for C46H51INaO14
977.2221, measured 977.2220.
+
22
0.25 (1:3, EtOAc/Hexane); [α]D = +27.4 (c 0.25, CHCl3); IR
(Neat): νmax 3052, 2720, 1719, 1686, 1272, 1370, 1032, 675 cm-1;
1H (400 MHz, CDCl3): δ 7.17-7.30 (m, 5H), 5.27 (bs, 1H), 5.19
(t, J=9.63 Hz, 1H), 5.06 (s, 1H), 4.86 (bs, 1H), 4.44-4.45 (m, 1H),
4.36-4.39 (m, 1H), 3.86-3.90 (m, 1H), 3.68-3.51 (m, 3H), 3.03
Acknowledgements
We are thankful to Mr. A. K. Pandey for technical assistance, and
SAIF, CDRI, for providing spectral data. P. S. and S. A. thank
CSIR for awarding Senior Research Fellowship. CDRI
manuscript no. 99/2016/AKS
(bs, 1H), 2.01 (s, 3H), 2.01 (s, 3H), 1.94 (s, 3H), 1.37 (s, 9H); 13
C
(100 MHz, CDCl3): δ 170.82, 170.10, 169.54, 155.40, 128.87,
127.75, 126.64, 100.71, 80.22, 71.08, 69.24, 69.16, 67.27, 62.03,
29.05, 28.57, 21.17, 20.93, 20.80; ESI-HRMS: m/z [M+Na]+
calcd for C25H34INNaO10+ 658.1125, measured 658.1138.
References:
[1]
(a) Kirschning, A.; Bechthold, A. F. W.; Rohr, J. In
(2R,3R,4S,5S,6R)-2-(acetoxymethyl)-5-iodo-6-(4-
Bioorganic Chemistry: Deoxy sugars, Polyketides and Related
Classes: Synthesis; Biosynthesis: Enzymes, 1997, 1; (b) He, X.;
Agnihotri, G.; Liu, H.-W. Chem. Rev. 2000, 100, 4615; (c) He,
X. M.; Liu, H. W. Curr. Opin. Chem. Biol. 2002, 6, 590; (d) De
Lederkremer, R. M.; Marino, C. Adv. Carbohydr. Chem.
Biochem. 2008, 61, 143.
methoxyphenoxy)tetrahydro-2H-pyran-3,4-diyl diacetate 16:
This compound was prepared by following above mentioned
general procedure III using isopropyl alcohol (0.05 mL, 0.24
mmol) as an acceptor; Yield: (95 mg, 0.186 mmol, 90%); Rf:
22
0.30 (1:3, EtOAc/Hexane); [α]D = +5.6 (c 0.1, CHCl3); IR
(Neat): νmax 3015, 2930, 2856, 1722, 1656, 1462, 1253, 1122,
[2]
(a) Henkel, T.; Rohr, J.; Beale, J. M.; Schwenen, L. J.
1
1063, 755, 665 cm-1; H (400 MHz, CDCl3): δ 6.94 (d, J=9.64
Antibiot. 1990, 43, 492; (b) Shaaban, K. A.; Srinivasan, S.;
Kumar, R.; Damodaran, C.; Rohr, J. J. Nat. Prod. 2011, 74, 2; (c)
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Chem., Int. Ed. Engl. 1991, 30, 1387.
Hz, 2H), 6.75 (d, J=9.64, 2H), 5.67 (s, 1H), 5.37 (t, J=9.64, 1H),
4.76 (dd, J1=4.48, J2=9.41 Hz, 1H), 4.66 (dd, J1=1.35, J2=4.43
Hz, 1H), 4.05-4.15 (m, 3H), 3.70 (s, 3H), 2.05 (s, 3H), 2.0 (s,
3H), 1.99 (s, 3H); 13C (100 MHz, CDCl3): δ 170.80, 170.11,
169.72, 155.70, 149.84, 118.04, 114.89, 100.76, 69.93, 69.20,
67.62, 62.24, 55.88, 29.16, 21.18, 20.91, 20.87 ESI-HRMS: m/z
[M+H]+ calcd for C19H24IO9+ 523.0465, measured 523.0450.
Lombo, F.; Menendez, N.; Salas, J. A.; Mendez, C.
[5]
[6]
Omura, S. Angew. Chem. Int. Ed. 2016, 55, 2 .
(a) Kubo, S.; Mimaki, Y.; Terao, M.; Sashida, Y.;
(2R,3R,4S,5S,6S)-2-(acetoxymethyl)-5-iodo-6-
isopropoxytetrahydro-2H-pyran-3,4-diyl diacetate 17: This
compound was prepared by adopting the above mentioned
general procedure III using 4-methoxyphenol (28 mg, 0.24
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Nikaido, T.; Ohmoto, T. Phytochemistry 1992, 31, 3969; (b)
Mimaki, Y.; Kuroda, M.; Kameyama, A.; Sashida, Y.; Hirano,
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22
0.30 (1:3, EtOAc/Hexane); [α]D = +32.4 (c 0.3, CHCl3); IR
[7]
(a) Kaluza, G.; Scholtissek, C.; Rott, R. A. J. Gen,
(Neat): νmax 3021, 2992, 2812, 1720, 1556, 1462, 1253, 1122, cm-
Virol. 1972, 14, 251; (b) Lagunas, R.; Moreno, E. yeast, 1992, 8,
107; (c) Sastry, M.; Patel, D. J. Biochemistry 1993, 32, 6588; (d)
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1997, 188, 1; (f) Ghaouth, A. E. C.; Wilson, L.; Wisniewski, M.
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56, 8385; (h) Zhu, Z.; Jiang, W.; McGinley, J. N.; Thompson, H.
J. Cancer Res. 2005, 65, 7023; (i) Daniel, P. T.; Koert, U.;
Schuppan, J. Angew. Chem., Int. Ed. 2006, 45, 872.
1
1; H (400 MHz, CDCl3): δ 5.35 (t, J=10 Hz, 1H), 5.25 (s, 1H),
4.64 (dd, J1=4.39, J2=9.40 Hz, 1H), 4.47 (dd, J1=1.31, J2=4.33
Hz, 1H), 4.20 (dd, J1=5.10, J2=12.38 Hz, 1H), 4.05-4.14 (m, 2H),
3.85-3.94 (m, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H), 1.22
(d, J=6.19 Hz, 3H), 1.16 (d, J=5.83 Hz, 3H); 13C (100 MHz,
CDCl3): δ 170.90, 170.06, 169.73, 99.90, 71.35, 69.36, 69.32,
68.04, 62.57, 30.79, 23.28, 21.85, 21.18, 20.93, 20.88; ESI-
HRMS: m/z [M+Na]+ calcd for C15H23INaO8 481.0335,
+
measured 481.0342.
[8]
(a) Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 14,
(2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(((2R,3R,5R,6S)-3,5-
bis(benzyloxy)-2-((benzyloxy)methyl)-6-(4-
methoxyphenoxy)tetrahydro-2H-pyran-4-yl)oxy)-5-
99; (b) Albrecht, H. P. Cardiac Glycosides. In Naturally
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1999; (c) Veyrie`res, A. In Carbohydrates in Chemistry and
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iodotetrahydro-2H-pyran-3,4-diyl
diacetate
18:
This
compound was prepared by adopting the above mentioned
general procedure III using glucose derived acceptor (120 mg,
0.24 mmol) as an acceptor; Yield: (170 mg, 0.19 mmol, 85%);
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22
Rf: 0.2 (1:3, EtOAc/Hexane); [α]D = -20.3 (c 0.2, CHCl3); IR
(Neat): νmax 3427, 3015, 2930, 1702, 1427, 1217, 1106, 919, 764
10

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11