Addition of amines and carbon nucleophiles to vinyl sulfone-modified 6-deoxy-hex-3-enopyranoside: a case of nucleophile dependent diastereoselectivity

Article abstract of DOI:10.1016/j.carres.2009.09.009

Reactions of amines and carbon nucleophiles with 4-sulfonyl-hex-3-enopyranoside generate a range of C-3 amino- and C-3 branched-chain sugars, which are analogues of 3-amino-3,6-dideoxy sugars and 3-C-branched-chain-3,6-dideoxy sugars. The diastereoselecti

Full text of DOI:10.1016/j.carres.2009.09.009

Carbohydrate Research 344 (2009) 2336–2341
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Addition of amines and carbon nucleophiles to vinyl sulfone-modified
6-deoxy-hex-3-enopyranoside: a case of nucleophile dependent
diastereoselectivity
*
Rahul Bhattacharya, Tanmaya Pathak
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2009
Received in revised form 2 September 2009
Accepted 9 September 2009
Available online 12 September 2009
Reactions of amines and carbon nucleophiles with 4-sulfonyl-hex-3-enopyranoside generate a range of
C-3 amino- and C-3 branched-chain sugars, which are analogues of 3-amino-3,6-dideoxy sugars and
3-C-branched-chain-3,6-dideoxy sugars. The diastereoselectivity of addition reaction is nucleophile
dependent; while both nitrogen and carbon nucleophiles added in cis-fashion, amines generated C3-C4
trans-diaxial products (gulo-derivatives), and carbon nucleophiles afforded C3–C4 trans-diequatorial
products (gluco-analogues).
Keywords:
Vinyl sulfone
Ó 2009 Elsevier Ltd. All rights reserved.
Modified carbohydrate
Michael addition
Aminosugar
Branched-chain sugar
Diastereoselectivity
1. Introduction
derivatives have also been used frequently for the synthesis of
3-amino-3,6-dideoxysugars.11,20–22 3-Amino-3-deoxygluco-deriva-
Aminosugars and branched-chain sugars are important classes of
modified carbohydrates.1,2 Several 3-amino-3,6-dideoxy sugars and
3-C-branched-chain-3,6-dideoxy sugars which belong to special
classes of amino- and branched-chain sugars are reported in the
literature. Some of these aminosugars such as ristosamine,3,4 daun-
osamine,3–6 ravidosamine,7,8 desosamine,9–12 and mycosamine13,14
are the structural components of either macrolide antibiotics such
as methamycine, pikromycine,13 and amphotericin B14 or tetracyc-
lins such as ravidomycine7,8 and daunomycin15 (Fig. 1).
tives were generated in a regioselective fashion from 6-deoxy ana-
logues of 2,3-anhydro allo-pyranosides.11 However because of the
nonselective regiochemical outcome,21 the 3,4-anhydro allo- and
galacto-pyranosides are not the substrates of choice.23 On the other
hand, use of C-3-ulopyranosides for the synthesis of C-3-N amino-
sugars are notably interesting compared to the other meth-
ods,13,20,21 although the reduction of such sugar-derived oxime
and hydrazone derivatives using common reducing agents afforded
a mixture of aminosugars.8,19 In the case of C–C bond formation,
nucleophilic displacement of C-3-O-sulfonylated carbohydrates
by carbon nucleophiles are of negligible interest because of the
secondary nature of the C-3 hydroxyl groups. Although ring-open-
ing reactions of sugar-derived epoxides by carbon nucleophiles are
known to be less efficient,23 limited number of 3-functionalized-
3,6-dideoxysugars were synthesized by reacting the corresponding
oxiranes with carbon nucleophiles.24–27 A minor method using
cyanopropionaldehyde diethylacetal and (S)-propyleneoxide gen-
erated a mixture of four methyl glycosides of 3-cyano-2,3,4-6-
tetradeoxysugars.28
Although there are a limited number of reports on the natural
occurrence of C-3-substituted-branched-chain sugars, D-aldgarose
is the best known example of this kind.16 However, a 3,6-dideoxy
branched-chain sugar,17 namely, methyl 2-O-benzoyl-3,6-dide-
oxy-3-C-methyl-a-D-altropyranoside was used for the construction
of the complex molecule rifamycin W. Yet another related sugar
reportedly exists as a component of a complex molecule callipelto-
side A, a novel class of antitumor agent (Fig. 2).18
In spite of the noted importance of C-3 functionalized 3,6-dide-
oxysugars, synthesis of this class of compounds remains a chal-
lenging task. Sugar triflates,12–14 epoxide,11 and ketones19,20 are
the commonly used intermediates for the incorporation of nitrogen
functionality at C-3 of 6-deoxy-hexopyranosides. 4,6-Dichloro
2. Results and discussion
Vinyl sulfone-modified pyranosides and furanosides function as
efficient Michael acceptors capable of generating a wide range of
products by reaction with several nucleophiles in a diastereoselec-
* Corresponding author.
E-mail address: tpathak@chem.iitkgp.ernet.in (T. Pathak).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.09.009

R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341
2337
ing both amino- and branched-chain sugars represented by the
general structure 2 (Scheme 1).
O
O
O
A retrosynthetic analysis of the route to 1 necessitated the
introduction of the tolylthio group at the C-4 position of a hexopyr-
anosyl sugar. One of the easiest ways of forming a C–S bond would
be the displacement of suitably oriented and protected sugar-sul-
fonates or the regioselective ring opening of epoxy-sugars with
sulfur nucleophiles. The use of any 3,4-anhydro sugars as starting
materials was ruled out because of the ambiguity of the ring-open-
ing reaction in terms of regioselectivity discussed above.21,23 More-
over, retrosynthetic analysis indicated that a higher number of
reaction steps would be required for the synthesis of suitably
substituted 3,4-anhydro sugar (gluco- and galacto-) compared to
the synthesis of gluco-mesylate 3. Thus, the sugar-derived mesy-
late 331 was reacted with p-tolylthiol in DMF in the presence of
TMG at about 150–160 °C to afford 4 in 89% yield within 5 h
(Scheme 2). The regio- and stereospecificities of attack of p-tolyl-
thiolate to C-4 position of 3 was a foregone conclusion because
HO
OH
HO
HO
N
N
HO
O
O
O
O
O
Me
O
Me
O
O
Methymycine
Pikromycine
OH
Me
HO
O
OH
O
OH OH
OH OH
O
O
Me
COOH
Me
Me
OH
O
NH2
Amphotericin B
OH
HO
OH
O
Me
Me
OH
of its inbuilt structural features. Thus, the a-gluco-mesylate 3 pro-
AcO
Me2N
O
O
duced galacto-derivative 4 as expected. Treatment of compound 4
with methanolic NaOMe at reflux temperature for 7 h afforded
compound 5 in excellent yield. The corresponding sulfone deriva-
tive 6 was generated in quantitative yield at room temperature
within 6 h by oxidizing 5 with magnesium monoperoxyphthalate
hexahydrate (MMPP) in MeOH. Compound 6 was subjected to
elimination reaction using MsCl in pyridine at +4 °C to afford 1 in
86% yield (Scheme 2). The identity of vinyl sulfone 1 was estab-
lished on the basis of spectroscopic and analytical data, the vinyl
proton appearing at d 6.85.
O
O
OH
O
OMe
O
HO
Me
OMe
OH OMe
NMe2
OH
Daunomycine
Ravidomycine
Figure 1. 3-Amino-3,6-dideoxysugars as components of macrolide antibiotics and
tetracyclins.
Me
O
OBz
Me
O
Me
HO
Me
Me
ArO2S
?
NuH
OH
O
OH
ArO2S
Nu
O
O
OMe
Me
O
?
methyl 2-O-benzoyl-3,6-dideoxy-
3-C-methyl-α-D-altropyranoside
O
BnO OMe
BnO
D-aldgarose
OMe
Ar = p-Tol
2
1
Scheme 1. Proposed reaction pattern of vinyl sulfone-modified carbohydrate 1.
H
N
O
O
Me
Me
R
O
p-TolSH, TMG
DMF, 140 OC
5 h, 89 %
STol-p
Me
MeO
Me
O
O
O
O
MsO
BzO
OH
BzO
O
O
Me
BnO
OMe
BnO
H
OMe
Cl
Cl
3
Me
4
R =
OMe
Me
MMPP,
MeOH,
rt, 6 h,
NaOMe,
MeOH
reflux,
STol-p
Me
Callipeltoside A
O
Figure 2. Selected examples of C-3-branched-3,6-dideoxysugars.
quantitative
7 h, 97 %
HO
BnO
tive fashion.29,30 This strategy would also be useful for producing a
number of 3-deoxy-3-modified carbohydrates. Barring a report on
the use of 2-sulfonyl-hex-2-enopyranoside as a Michael acceptor
and another describing the use of 4-sulfonyl-hex-3-enopyranoside
as a partner in a cycloaddition reaction, this strategy for the func-
tionalization of the C-3 carbon of a vinyl sulfone-modified carbo-
hydrate remains unexplored.29,30 In the light of the above
discussion and in order to study the scope of C-3 functionalization
we intended to synthesize and study the reaction patterns of a 4-
OMe
5
SO2Tol-p
Me
O
MsCl, Py
0 oC to + 4 oC
16 h, 86%
1
HO
BnO
OMe
6
sulfonyl-hex-3-enopyranoside
1
derived from
D-glucose. We
Scheme 2. Synthesis of methyl 2-O-benzyl-3,4,6-trideoxy-4-(4-methylphenyl)-
sulfonyl- -erythro-hex-3-enopyranoside 1.
opined that a Michael acceptor like 1 is highly capable of generat-
a-D

2338
R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341
Compound 1 on reaction with neat benzylamine at 80–90 °C
spectral data of amino-derivatives 8 (d 4.71, J = 3.6 Hz, H-1), 10 (d
4.94, J = 3.6 Hz, H-1), and 7 (d 4.74, J = 3.6 Hz, H-1) we concluded
that amine adducts 8–10 were having D-gulo conformation as well.
The identities of compounds 11 (Fig. 4) and 12 (Fig. 5) were estab-
lished unambiguously by the X-ray analysis of their single crystals
and the compounds were found to have D-gluco configuration.
Since amines were expected to add to the C-3 position of 1 from
a direction opposite to that of the disposition of the C-2 benzyloxy
generated a mixture (TLC) from which the major product 7 was
isolated in 79% yield (Scheme 3). Similarly, reaction of 1 with neat
n-butylamine at elevated temperature afforded 8 in 83% yield. Aq
ammonia (30%) at room temperature produced a mixture from
which the major product 9 was isolated in 81% yield; the product
was however characterized as the N-benzoyl derivative 10. Com-
pound 1 on the other hand, on reaction with carbon nucleophiles
generated from nitromethane or dimethylmalonate in the presence
of t-BuOK in THF at reflux temperature, afforded single compounds
11 and 12 in 73% and 78% yields, respectively (Scheme 3).
group to afford a D-gluco derivative having four (C2, C3, C4, and C5)
equatorial bonds, the formation of products with C–N axial bond at
C-3 and C–S axial bond at C-4 surprised us. However, it is reported
that the addition of neutral species like amines to a Michael accep-
tor may take place through concerted mechanism involving a pro-
ton relay process.32 Considering the same mechanistic pathway,
we propose that cis-addition of amines to compound 1 takes place
to generate the trans-diaxial product (Scheme 4). Thus, it is plausi-
ble that the preferential formation of trans-diaxial geometry in the
transition state over the trans-diequatorial geometry resulted from
the positioning of amines via a six-membered transition state as
depicted in Scheme 4. It is also probable that an additional H-bond-
ing such as R–NꢀꢀꢀHꢀꢀꢀOMe stabilized the transition state further to
such an extent that the formation of tetra-equatorial products
(such as 11 and 12) was overruled in favor of the formation of
C3–C4 diaxial products 7–9.33–35
The structure of compound 7 was unambiguously established as
the gulo-derivative from X-ray crystal structure analysis of the sin-
gle crystal of compound 7 (Fig. 3). On the basis of similarities of the
SO2Tol-p
neat amines
or
aq. NH3
Me
O
BnO
NHR
OMe
7 R = Bn (79%)
8 R = n-Bu (83%)
9 R = H (81%)
10 R= Bz
1
BzCl, Py, rt,
20 h, 88%
CH3NO2
or
Me
O
H2C(COOMe)2
p-TolO2S
R
KOBu-t, THF,
80 ºC, 10-12 h
BnO
OMe
11 R = CH2NO2 (73%)
12 R = CH(CO2Me)2 (78%)
Scheme 3. Reactions of vinyl sulfone-modified 6-deoxy-hex-3-enopyranoside 1
with amines and carbon nucleophiles.
Figure 4. ORTEP diagram of compound 11.
Figure 3. ORTEP diagram of compound 7.
Figure 5. ORTEP diagram of compound 12.

R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341
2339
7.14 (d, 2H, J = 8.0 Hz); 7.21–7.39 (m, 8H); 7.49–7.56 (m, 1H);
7.81–7.85 (m, 1H). 13C NMR: d 18.5, 21.6, 55.4, 57.6, 65.3, 73.3,
73.4 (CH2), 74.6, 98.7, 127.8, 127.9, 128.0, 128.4, 129.5, 129.6,
129.9, 132.0, 132.1, 132.7, 136.6, 138.1, 165.8. Anal. Calcd for
C24H30O5Sꢀ0.5H2O: C, 63.95; H, 6.77. Found: C, 63.86; H, 7.03.
CH3
p-TolO2S
O
H
H
H
7-9
OBn
OMe
R
N
N
R
H
3.3. Methyl 2-O-benzyl-4,6-dideoxy-4-(4-methylphenyl)-
sulfide-a-D-galactopyranoside 5
H
To a solution of 4 (2.0 g, 4.18 mmol) in methanol (30 mL) was
added NaOMe (0.3 g, 5.55 mmol) and the resulting solution was
heated under reflux for 7 h, cooled to rt and the solvent was evapo-
rated. The residue thus obtained was dissolved in EtOAc (30 mL).
The organic layer was washed with satd aq NH4Cl solution
(2 ꢁ 20 mL) and separated. The organic layer was dried over anhyd
Na2SO4, and evaporated under reduced pressure to get crude 5.
The crude product was purified over silica gel to get pure compound
Scheme 4. Proposed concerted proton relay process leading to the formation of
D-gulo derivatives 7–9.
Compound 3 on reaction with nitromethane and dimethylmal-
onate generated the expected and thermodynamically more stable
C3–C4 diequatorial products. Although it is tempting to argue that
the bulky benzyloxy substituent at C-2 was responsible for the par-
ticular diastereoselectivity of the addition of carbon nucleophiles
5 (1.63 g, 97%). [Eluent: EtOAc/pet ether (3:17)]. Colorless jelly. ½a D30
ꢂ
at C-3, it is also highly probable that the anomeric
a-methoxy
+48.4(c 0.625, CHCl3). 1H NMR(CDCl3): d 1.36 (d, 3H, J = 6.4 Hz); 2.31
(s, 3H); 2.79 (br s, 1H); 3.33 (s, 3H); 3.39–3.41 (m, 1H); 3.46–3.50 (m,
1H); 4.20–4.29 (m, 2H); 4.60 (d, 1H, J = 3.6 Hz); 4.74 (dd, 2H,
J = 12.0 Hz, 50.8 Hz); 7.09 (d, 2H, J = 8.0 Hz); 7.28–7.43 (m, 7H). 13C
NMR: d 18.4, 21.0, 55.3, 62.8, 65.6, 69.3, 73.1 (CH2), 78.3, 98.3,
127.9, 128.1, 128.4, 129.8, 132.0, 133.1, 137.1, 138.1. Anal. Calcd
for C21H26O4SꢀH2O: C, 67.91; H, 6.04. Found: C, 67.84; H, 5.51.
group which stabilized the transition state in case of amines
(Scheme 4), stereoelectronically repelled the incoming negatively
charged carbon nucleophiles so that these nucleophiles were
forced to attack the electron deficient C-3 position of 1 from the
b-face of the sugar ring.33–35
In conclusion, the study on the reaction pattern of the hitherto
unknown 6-deoxy-4-sulfonyl-hex-3-enopyranoside 1 highlights
once again on the efficiency and diastereoselectivity of the addition
of nitrogen and carbon nucleophiles to such systems. This vinyl
sulfone-modified carbohydrate is capable of generating rare ami-
3.4. Methyl 2-O-benzyl-4,6-dideoxy-4-(4-methylphenyl)-
sulfonyl-a-D-galactopyranoside 6
nosugars having a
ing molecule generates less known C-3 branched-chain sugars
with -gluco configuration.
D-gulo configuration. In contrast, the same start-
To a solution of compound 5 (1.64 g, 4.18 mmol) in MeOH
(30 mL) was added MMPP (8.27 g, 16.72 mmol). The reaction mix-
ture was stirred for 6 h at ambient temperature, filtered, and the
filtrate was evaporated under reduced pressure. The resulting res-
idue was neutralized with satd aq NaHCO3 (70 mL). The mixture
was extracted with EtOAc (3 ꢁ 30 mL). The organic layer was sep-
arated and dried over anhyd Na2SO4 and filtered. The filtrate was
concentrated to dryness under reduced pressure and purified over
silica gel to yield compound 6 (1.6 g, quantitative). [Eluent: EtOAc/
D
3. Experimental
3.1. General methods
All reactions were conducted under N2 atmosphere. Melting
points were determined in open-end capillary tubes and are uncor-
rected. Carbohydrates and other fine chemicals were obtained from
commercial suppliers and are used without purification. Solvents
were dried and distilled following the standard procedures. TLC
was carried out on pre-coated plates (Merck Silica Gel 60, f254) and
the spots were visualized with UV light or by charring the plate
dipped in 5% H2SO4–MeOH solution. Column chromatography was
performed on silica gel (230–400 mesh). 1H and 13C NMR for most
of the compounds were recorded at 200/400 and 50/100 MHz,
respectively, using either CDCl3 as the solvent unless stated other-
wise. DEPT experiments have been carried out to identify the meth-
ylene carbons. Optical rotations were recorded at 589 nm.
pet ether (1:4)]. Colorless jelly. ½a D30
ꢂ
+47.3 (c 0.62, CHCl3). 1H NMR
(CDCl3): d 1.68 (d, 3H, J = 7.2 Hz); 2.47 (s, 3H); 3.43 (s, 3H); 3.73–
3.77 (m, 2H); 3.86 (d, 1H, J = 2.4 Hz); 4.13–4.14 (m, 1H); 4.53–
4.58 (m, 2H); 4.71 (d, 1H, J = 12.0 Hz); 4.89 (s, 1H); 7.14–7.31 (m,
5H); 7.35 (d, 2H, J = 8.0 Hz); 7.75 (d, 2H, J = 8.0 Hz). 13C NMR: d
17.5, 21.6, 56.3, 63.8, 66.9, 68.4, 73.6 (CH2), 75.4, 95.8, 127.7,
127.8, 128.1, 128.2, 129.9, 136.6, 137.9, 145.1. Anal. Calcd for
C21H26O6S: C, 67.04; H, 6.82. Found: C, 67.20; H, 75.
3.5. Methyl 2-O-benzyl-3,4,6-trideoxy-4-(4-methylphenyl)-
sulfonyl-a-D-erythro-hex-3-enopyranoside 1
3.2. Methyl 2-O-benzyl-3-O-benzoyl-4,6-dideoxy-4-
(4-methylphenyl)-sulfide-a-D-galactopyranoside 4
To a solution of 6 (1.0 g, 2.46 mmol) in dry pyridine (15 mL) was
added methanesulfonyl chloride (0.55 mL, 7.4 mmol) in dry pyri-
dine (5 mL) at 0 °C. The mixture was left overnight at 4 °C. The
reaction mixture was poured into satd aq NaHCO3 (70 mL) and
aq phase was extracted with dichloromethane (3 ꢁ 30 mL). Organ-
ic extracts were pooled together, dried over anhyd Na2SO4, and fil-
tered. Et3N (5 mL) was added to the filtrate and after 15 min the
solvent was evaporated under reduced pressure. The resulting res-
idue was purified over silica gel to get 1 (0.79 g, 83%). [Eluent:
To a well-stirred solution of p-thiocresol (3.45 g, 27.77 mmol)
and TMG (3.31 g, 26.36 mmol) in dry DMF (20 mL) was added a
solution of the known compound 3 (2.5 g, 5.55 mmol) in dry
DMF (10 mL). The resulting solution was heated at 140–150 °C un-
der N2 for a period of 6 h, cooled to rt, and poured into satd aq NaCl
solution (80 mL). The mixture was extracted with EtOAc
(3 ꢁ 30 mL) and separated. The EtOAc layer was dried over anhyd
Na2SO4, and evaporated under reduced pressure. The resulting syr-
up was purified over silica gel to yield 4 (2.36 g, 89%). [Eluent:
EtOAc/pet ether (1:4)] White solid. Mp: 156–157 °C. ½a D30
ꢂ
+27.1 (c
0.30, CHCl3). 1H NMR (CDCl3): d 1.34 (d, 3H, J = 6.5 Hz); 2.43 (s,
3H); 3.33 (s, 3H); 4.16–4.27 (m, 2H); 4.66–4.76 (m, 3H); 6.85 (d,
1H, J = 1.26 Hz); 7.25–7.43 (m, 7H); 7.74 (d, 2H, J = 8.0 Hz). 13C
NMR: d 19.7, 21.5, 55.6, 64.3, 71.4, 71.7 (CH2), 96.1, 127.8, 128.0,
128.1, 128.5, 129.7, 135.4, 136.5, 137.0, 142.2, 144.4. Anal. Calcd
for C21H24O5Sꢀ0.5CHCl3: C, 57.62; H, 5.51. Found: C, 57.65; H, 5.39.
EtOAc/pet ether (1:19)] Colorless jelly. ½a D30
ꢂ
+52.2 (c 1.14, CHCl3).
1H NMR (CDCl3): d 1.42 (d, 3H, J = 6.4 Hz); 2.07 (s, 3H); 3.36 (s,
3H); 3.84–3.87 (m, 1H); 4.14–4.21 (m, 1H); 4.36–4.45 (m, 1H);
4.66–4.82 (m, 3H); 5.54–5.61 (m, 1H); 6.74 (d, 2H, J = 8.0 Hz);

2340
R. Bhattacharya, T. Pathak / Carbohydrate Research 344 (2009) 2336–2341
3.6. Methyl 2-O-benzyl-3,4,6-trideoxy-3-benzylamino-4-
(4-methylphenyl)-sulfonyl- -gulopyranoside 7
added dropwise to the reaction mixture. The resulting solution
was then heated under reflux with continuous stirring under N2
for 12 h. The reaction mixture was cooled to room temperature
and the volatile matters were evaporated under reduced pressure.
The residue obtained was triturated with EtOAc (30 mL). The or-
ganic layer was washed with satd aq solution of NH4Cl
(3 ꢁ 30 mL) and separated. The organic layer was dried over anhyd
Na2SO4, filtered, and the filtrate was evaporated under reduced
pressure to get a residue. The crude residue was purified by col-
umn chromatography over silica gel to obtain 11. (0.13 g, 73%).
[Eluent: EtOAc/pet ether (1:4)]. White crystalline solid. Mp: 137–
a-D
A mixture of 1 (0.2 g, 0.5 mmol) and neat benzylamine (3 mL)
was heated at 90 °C for 16 h with continuous stirring under N2.
The reaction mixture was cooled to room temperature and the vol-
atile matters were evaporated under reduced pressure. The residue
obtained was dissolved in EtOAc (30 mL). The EtOAc layer was
washed with satd aq solution of NH4Cl (3 ꢁ 30 mL) and separated.
The organic layer was then dried over anhydrous Na2SO4, filtered,
and the filtrate was evaporated under reduced pressure to get a
residue. The crude residue was purified by column chromatogra-
phy over silica gel to get 7 (0.136 g, 79%). [Eluent: EtOAc/pet ether
139 °C. ½a 2D8
ꢂ
+34.3 (c 0.625, CHCl3). 1H NMR (CDCl3): d 1.30 (d,
3H, J = 6.4 Hz); 2.46 (s, 3H); 2.87–2.94 (m, 1H); 3.18 (s, 3H);
3.49–3.55 (m, 2H); 3.88–3.92 (m, 1H); 4.47 (d, 1H, J = 3.2 Hz);
4.55 (dd, 2H, J = 11.6, 18.4 Hz); 5.06–5.10 (m, 1H); 5.19–5.24 (m,
1H); 7.29–7.40 (m, 7H); 7.76 (d, 2H, J = 8.0 Hz). 13C NMR: d 21.1,
21.6, 34.8, 55.2, 62.9, 66.0, 72.6 (CH2), 73.8 (CH2), 75.4, 95.2,
128.2, 128.3, 128.6, 128.8, 130.1, 135.0, 137.1, 145.5. Anal. Calcd
for C22H27NO7Sꢀ0.5H2O: C, 64.90; H, 6.19; N, 2.07. Found: C,
64.90; H, 5.99; N, 1.95.
(1:3)] White crystalline solid. Mp: 127–129 °C. ½a D28
ꢂ
+34.1 (c 0.625,
CHCl3). 1H NMR (CDCl3): d 1.51 (d, 3H, J = 6.8 Hz); 2.44 (s, 3H),
3.15–3.16 (m, 1H), 3.28–3.30 (m, 1H), 3.41 (s, 3H); 3.57 (dd, 2H,
J = 13.6, 36.0 Hz), 3.99–4.02 (m, 1H); 4.37 (dd, 2H, J = 12.4,
32.8 Hz); 4.69–4.72 (m, 1H); 4.74 (d, 1H, J = 3.6 Hz); 7.01–7.02
(m, 2H); 7.19–7.26 (m, 7H); 7.29–7.36 (m, 3H); 7.46 (d, 2H,
J = 8.0 Hz). 13C NMR: d 18.4, 21.8, 52.7 (CH2), 52.8, 55.3, 60.7,
68.8 (CH2), 75.0, 96.0 (CH), 101.2 (CH), 118.0 (C), 120.6 (CH and
C), 122.8 (C), 126.6 (CH), 128.3 (CH), 129.1 (CH), 138.5 (C). 160.6
(C). Anal. Calcd for C28H33NO5Sꢀ0.5CH3OH: C, 62.45; H, 6.77; N,
3.03. Found: C, 62.63; H, 5.51; N, 2.96.
3.10. Methyl 2-O-benzyl-3,4,-trideoxy-3-C-
bis(methoxycarbonyl)methyl-4-(4-methylphenyl)-
sulfonyl-D-glucopyranoside 14
3.7. Methyl 2-O-benzyl-3,4,6-trideoxy-3-(n-butyl)amino-4-
(4-methylphenyl)-sulfonyl-a-D-gulopyranoside 8
Compound 1 (0.2 g, 0.5 mmol) was treated with dimethylmalo-
nate (0.15 mL, ꢃ2.5 mmol) following the procedure described for
the preparation of 11 to get compound 12 within 10 h. (0.14 g,
78%). [Eluent: EtOAc/pet ether (2:7)] White crystalline solid. Mp:
Compound 1 (0.2 g, 0.5 mmol) was treated with neat n-butyl-
amine (3 mL) at 80 °C following the procedure described for 7 to
get compound 8 within 14 h (0.142 g, 83%). [Eluent: EtOAc/pet
142–144 °C. ½a 2D8
ꢂ
+37.1 (c 0.625, CHCl3). 1H NMR (CDCl3): d 1.45
(d, 3H, J = 5.6 Hz); 2.45 (s, 3H); 2.99–3.05 (m, 4H); 3.14–3.20 (m,
1H); 3.47 (s, 3H); 3.79 (s, 3H); 3.80–3.84 (m, 1H); 4.22 (d, 1H,
J = 2.8 Hz); 4.26–4.35 (m, 2H); 4.45 (d, 1H, J = 11.6 Hz); 4.77 (d,
1H, J = 3.2 Hz); 7.22–7.29 (m, 5H); 7.37 (d, 2H, J = 8.0 Hz); 7.77
(d, 2H, J = 8.0 Hz). 13C NMR: d 21.6, 21.9, 36.4, 49.6, 52.2, 52.3,
54.9, 62.6, 68.2, 72.8 (CH2), 75.0, 95.6, 127.9, 128.2, 128.6, 129.3,
129.8, 134.1, 137.7, 145.1. Anal. Calcd for C26H32O9Sꢀ0.5H2O: C,
62.67; H, 5.59. Found: C, 62.40; H, 5.82.
ether (1:4)]. White crystalline solid. Mp: 123–125 °C. ½a D28
ꢂ
+28.1
(c 0.625, CHCl3). 1H NMR (CDCl3): d 0.80 (t, 3H, J = 6.8 Hz); 1.14–
1.18 (m, 5H); 1.52 (d, 3H, J = 7.2 Hz); 2.31–2.34 (m, 2H); 2.43 (s,
3H), 3.22–3.25 (m, 2H), 3.39 (s, 3H); 4.00–4.02 (m, 1H), 4.58–
4.64 (m, 3H); 4.71 (d, 1H, J = 3.6 Hz); 7.26–7.38 (m, 7H); 7.66 (d,
2H, J = 8.4 Hz). 13C NMR: d 13.9, 18.3, 20.3 (CH2), 21.7, 31.9 (CH2),
49.0 (CH2), 54.2, 55.9, 61.0, 67.8, 71.3, 71.6 (CH2), 98.9, 128.0,
128.1, 128.2, 128.5, 129.7, 137.7, 137.8, 144.5. Anal. Calcd for
C25H36NO5Sꢀ0.5CH3OH: C, 65.62; H, 7.40; N, 2.89. Found: C,
65.69; H, 7.57; N, 2.79.
Acknowledgments
T.P. thanks the Indo-French Centre for the Promotion of Ad-
vanced Research, New Delhi for funding (Project No. 3405-1). R.B.
thanks CSIR, New Delhi for a fellowship. DST is also thanked for
the creation of 400 MHz facility under IRPHA program and DST-
FIST for single crystal X-ray facility.
3.8. Methyl 2-O-benzyl-3,4,6-trideoxy-3-(N-benzoyl)amino-4-
(4-methylphenyl)-sulfonyl-a-D-gulopyranoside 10
Compound 1 (0.2 g, 0.5 mmol) was treated with aq ammonia at
room temperature to get compound 9 within 36 h. Compound 9
was benzoylated using standard procedure to afford 10 (0.18 g,
88% from 1). [Eluent: EtOAc/pet ether (1:6)]. Colorless jelly. ½a D28
ꢂ
Supplementary data
+54.1 (0.625, THF). 1H NMR (CDCl3): d 1.58 (d, 3H, J = 6.8 Hz);
2.46 (s, 3H), 3.51 (s, 3H); 3.75–3.77 (m, 1H), 4.29–4.31
(m, 1H); 4.46–4.58 (m, 3H); 4.65–4.69 (m, 1H); 4.49 (d, 1H,
J = 3.6 Hz); 7.26–7.34 (m, 5H); 7.38–7.52 (m, 5H); 7.70 (d, 2H,
J = 7.2 Hz); 7.83 (d, 2H, J = 8.4 Hz). 13C NMR: d 18.4, 21.8, 46.7,
56.2, 60.9, 64.9, 69.3, 70.9 (CH2), 99.3, 127.0, 128.0, 128.2
(2 ꢁ CH), 128.6, 128.7, 130.0, 131.9, 133.6, 137.0, 137.1, 145.0,
167.0. Anal. Calcd for C28H31NO6Sꢀ0.5H2O: C, 63.40; H, 5.60; N,
2.76. Found: C, 63.22; H, 5.62; N, 2.29.
Complete crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre,
CCDC Nos. 742104–742106. Copies of this information may be ob-
tained free of charge from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB21EZ, UK. (fax: +44-
1223-336033, e-mail: deposit@ccdc.cam.ac.uk or via: www.
ccdc.cam.ac.uk), and spectra of 1, 4–8, 10–12. Supplementary data
associated with this article can be found, in the online version, at
doi:10.1016/j.carres.2009.09.009.
3.9. Methyl 2-O-benzyl-3,4,6-trideoxy-3-C-nitromethyl-4-
(4-methylphenyl)-sulfonyl-a-D-glucopyranoside 11
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