Triazole-fused sugars from nitroalkene-containing C-glycosides by a tandem 1,3-dipolar cycloaddition and intramolecular Michael addition

Article abstract of DOI:10.1016/j.carres.2009.03.007

A synthetic method to triazole-fused sugars by treatment of nitroalkene-containing C-glycosides with sodium azide is described. Initial experiments conducted at room temperature gave only the 1,3-dipolar cycloaddition products. However, at elevated reacti

Full text of DOI:10.1016/j.carres.2009.03.007

Carbohydrate Research 344 (2009) 1024–1027
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Note
Triazole-fused sugars from nitroalkene-containing C-glycosides by a tandem
1,3-dipolar cycloaddition and intramolecular Michael addition
*
Wei Zou , Milan Bhasin, Kannan Vembaiyan, Dean T. Williams
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6
a r t i c l e i n f o
a b s t r a c t
Article history:
A synthetic method to triazole-fused sugars by treatment of nitroalkene-containing C-glycosides with
sodium azide is described. Initial experiments conducted at room temperature gave only the 1,3-dipolar
cycloaddition products. However, at elevated reaction temperature the tandem b-elimination/cycloaddi-
tion/Michael addition yielded 1,5-disubstituted triazole-fused sugars.
Received 26 January 2009
Received in revised form 27 February 2009
Accepted 7 March 2009
Available online 12 March 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
Synthesis
Triazole
C-Glycoside
Nitroalkene
Cycloaddition
Michael addition
1,2,3-Triazoles are often synthesized from organic azides and
alkynes by 1,3-dipolar cycloaddition.1 The reaction can be induced
thermally and by Cu(I) catalysts.2 In addition to being structural
entities of antibacterial and anti-tumour agents,3 the formation
of triazoles is widely used in molecular ligation of bioactive carbo-
hydrates with various carrier molecules.4 Our interest in triazole-
fused sugars as potential glycosidase inhibitors5 has prompted
the current synthetic study.
Triazole-fused sugars have been synthesized by intramolecular
1,3-dipolar cycloadditions of an azido group to a carbon–carbon
multiple bond of substrates such as an unsaturated ester6 and an
alkyne group.7 More recently, an In(OTf)3-catalyzed one-pot reac-
tion between trimethylsilylazide (TMSN3) and 1,1-dimethoxyhex-
5-yne derivatives also afforded triazole-fused sugars.8 There are
also reports in which aromatic nitroalkenes were used as a replace-
ment of the alkyne to react with sodium azide9 and TMSN310 lead-
ing to 1,2,3-triazoles (Scheme 1). The products obtained by Zefirov
et al.9 were assigned as 2H-1,2,3-triazoles, while those reported by
Vaccaro et al.10 were assigned as 1H-1,2,3-triazoles. The 1,3-dipo-
lar cycloaddition between nitroalkene and azido compounds is af-
fected by electronic polarization of the substrates. An electron-
donating substituent at C2 of 1-nitroalkene, for example, a substi-
tuted aryl group, is often required to facilitate the reaction. In this
report, we describe a tandem 1,3-dipolar cycloaddition and intra-
molecular Michael addition from nitroalkene C-glycosides and so-
dium azide, leading to the formation of fused triazole-sugars.
Previously, we have used nitroalkyl 20-(oxoalkyl)-C-glycosides
for the synthesis of hydroxylated indoles and oxindoles by an
intramolecular Michael addition.11 The intermediates in that study,
D-ribosyl derivative 1 and L-arabinosyl derivative 5, can be easily
converted into nitroalkene C-glycosides (4 and 7) by oxidation of
the allyl group to a ketone (3 and 6) prior to the dehydration to
nitroalkenes (Scheme 2). 20-Oxidation of 1 and 5 was achieved
effectively using Hg(OAc)2 and Jones reagent as previously de-
scribed,12 which was followed by the treatment of 3 and 6 with
MsCl/TEA13 to afford nitroalkenes 4 and 7, respectively.
When nitroalkenes 2 and 4 were treated overnight with sodium
azide at room temperature, triazoles 8 and 9 were obtained in
moderate yields (see Scheme 3). Improved yields (60–70%) were
obtained when the substrate (e.g., 7) was treated with TMSN3
and t-butylammonium fluoride (TBAF)10 (see Scheme 3). 1H-
1,2,3-Triazole and 2H-1,2,3-triazole are tautomeric structures pre-
sented in 8–10 as evidenced by missing the C5 and C6 resonances
in their C-13 spectra. However, the cycloaddition likely produced
the latter because when 1-nitrocyclohexene (11) was treated with
sodium azide, the major product obtained was 2-N-substituted tri-
azole 12. Apparently, the intermediate 2H-1,2,3-triazole 13 was
initially formed and then trapped immediately by nitroalkene 11
via an intermolecular Michael-type addition (Scheme 4). Six dis-
tinctive 13C NMR signals for the nitrohexyl moiety and an addi-
tional three on triazolo-[4,5]-cyclohexane were observed. 1H
NMR also showed only two sets of chemical shifts for protons of
* Corresponding author. Tel.: +1 613 991 0855; fax: +1 613 952 9092.
E-mail address: wei.zou@nrc-cnrc.gc.ca (W. Zou).
0008-6215/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.carres.2009.03.007

W. Zou et al. / Carbohydrate Research 344 (2009) 1024–1027
1025
NO
H
2
N
NH
N
N
N
X
N
N
O N
2
O N
2
X
NaN /DMF
X
3
N
N
NaN /DMF
3
or
or TMSN /Bu NF
3
4
R
R
12
+ 11
R
11
X = CN, H
H
N
Scheme 1.
N
N
NO
NO
13
Scheme 4.
2
2
NO
2
OH
O
OH
O
O
a
b
O
O
OBn
OBn
OBn
OBn
OBn
OBn
4
3
1
69%
60%
the presence of a triazole moiety may actually hinder b-elimina-
tion. Treatment of 4 and 7 with sodium azide at elevated temper-
ature, however, afforded fused triazole-sugars (Scheme 5). It
appears that b-elimination at high temperature was followed by
1,3-dipolar cycloaddition of the azide to the nitroalkene group.
The open-chain intermediate, a conjugated ketone containing a tri-
azole moiety, then underwent an intramolecular Michael addition
to give a triazole-fused sugar. The stereochemistry of the reaction
was controlled similarly by thermodynamic stability of the transi-
tion state as previously reported,14 which led to the formation of a
fused triazole (14) from nitroalkene 4 and an anomeric mixture of
15 and 16 from nitroalkene 7. The low chemical yield was likely
the result of a series of side-reactions, including intermolecular
couplings similar to that reported in Scheme 4 as indicated by a
significant amount of very polar byproducts observed on TLC.
Based on the reaction illustrated in Scheme 4 2,4-disubstituted
triazoles would be the likely products (see Chart 1). However,
structural analysis of 14–16 by NMR, including the measurement
of coupling constants and NOE’s and comparison of our NMR data
b
NO
2
O
OBn
OBn
2
OBn
O
OBn
OBn
O
O
a
O
O
b
OBn
OBn
OH
OBn
OH
NO
NO
2
NO
2
7
2
6
5
(45% for two steps)
α/β 1:1
Scheme 2. Reagents and conditions: (a) Hg(OAc)2/Jones reagent; (b) MsCl/TEA in
DCM.
N
N
N H
N
NO
2
(J1,2 = 8.4 Hz, J3,4 = 4 Hz observed in 14, all small couplings in 15,
***
O
J1,2 = 3.2 Hz, J2,3 = 5.6 Hz and J3,4 = 4.0 Hz in 16 and
dc 132–
a (51%)
a (47%)
O
133 ppm for C-6 and 135–136 ppm for C-5) with those reported
in the literature6–8 suggest that the products could be 1,5-disubsti-
tuted triazoles.
OBn
OBn
OBn
OBn
OBn
2
8
NO
2
To determine unambiguously the bicyclic structure, we decided
to introduce 15N-atom into triazole 14 by treatment of 1-15N-so-
dium azide with nitroalkene 4. The triazole product obtained
(14-15N) was analyzed by 1H and 13C NMR. Because of the 15N label
at N-1 and N-3 of the triazole, based on 15N–13C and/or 15N–1H
couplings one would be able to definitively assign the structure
of 14. Although 15N–1H-6 coupling was observed in 14-15N at dH
7.69 ppm, 15N–1H-1 coupling was not conclusive due to the over-
lap of H-1 and benzyl CH2 proton resonances. However, the obser-
vation of 15N–13C-5, 15N–13C-6 and 15N–13C-1 coupling in 14-15N at
N H
N
O
O
O
O
O
O
OBn
4
OBn
OBn
OBn
9
OBn
O
OBn
O
a (40%)
or b (65%)
OBn
N
N H
7
NO
2
N
10
Scheme 3. Reagents and conditions: (a) NaN3 in DMF at rt overnight; (b) TMSN3/
N
N
TBAF.
HO
a
a
N
O
4
7
+
9
BnO
8%
OBn
14 (47%)
triazolo-[4,5]-cyclohexane, dH 1.81 (broad singlet, 4H, 2 ꢀ N@C–
CH2CH2) and 2.66 (broad singlet, 4H, 2 ꢀ N@C–CH2CH2), confirm-
ing the structure of 12 and that the 2H-triazole was indeed formed
from 1,3-dipolar addition.
N
N
N
HO
N
HO
BnO
N
O
N
O
+
BnO
OBn
16 (10%)
The formation of adduct 12 prompted us to attempt an intramo-
lecular Michael addition using triazoles 9 and 10 as substrates after
OBn
15 (23%)
b-elimination under basic conditions yielded an a,b-conjugated ke-
Reagents and conditions:(a) NaN in DMF at 80 ºC overnight
3
tone. However, both 9 and 10 were relatively stable under basic
conditions (1% NaOMe and K2CO3 in methanol), indicating that
Scheme 5. Reagents and conditions: (a) NaN3 in DMF at 80 °C overnight.

1026
W. Zou et al. / Carbohydrate Research 344 (2009) 1024–1027
15N
The organic phase was washed with brine, dried and evaporated.
N15
N15
N
HO
N
O
Purification by chromatography (hexane–EtOAc 8:1) yielded
1.33 g of product (69%). 1H NMR (CDCl3) d: 2.08 (s, 3H, CH3), 2.79
(dd, 1H, H-10a, J = 6.4, 17.6 Hz), 2.91 (dd, 1H, H-10b, J = 8.0,
17.6 Hz), 3.86 (dd, 1H, H-2, J = 4.0, 8.4 Hz), 4.19 (dd, 1H, H-3,
J = 4.0, 4.0 Hz), 4.45 and 4.83 (d and d, 1H each, CH2Ph,
J = 11.2 Hz), 4.51 (m, 1H, H-1), 4.54 and 4.71 (d and d, 1H each,
CH2Ph, J = 12.0 Hz), 4.64 (m, 1H, H-4), 7.06–7.15 (m, 2H, H-5, 6),
15N
O
HO
BnO
BnO
OBn
2,4-disubstituted triazole
OBn
1,5-disubstituted triazole
Chart 1.
13
7.23–7.39 (m, 10H, 2 ꢀ Ph); C NMR (CDCl3) d: 30.8 (C-30), 43.9
136.0 ppm (C-5), 132.5 ppm (C-6) and 54.0 ppm (C-1) indicates
that the products are indeed 1,5-disubstituted triazoles.
In summary, we described a synthetic method to triazole-fused
sugars from nitroalkene-containing C-glycosides. Initial experi-
ments conducted at room temperature gave only the 1,3-dipolar
cycloaddition products. However, at elevated reaction temperature
the tandem b-elimination/cycloaddition/Michael addition yielded
1,5-disubstituted triazole-fused sugars.
(C-10), 73.6 (CH2Ph), 74.3 (CH2Ph), 75.9 (C-4), 76.9 (C-1 and C-3),
84.2 (C-2), 128.2, 128.4, 128.7, 137.0 (C-5), 138.1 (C-6), 139.8,
140.2, 206.9 (C-20). HRMS: calcd for C23H26NO6 (M + H) 412.1760,
found 412.1748.
1.2.2.2. 1-C-(2,3-Di-O-benzyl-6-C-nitro-6-deoxy-a/b-D-arabino-
hex-5-eno-furanosyl)acetone (7). The compound (syrup) was
synthesized as an anomeric mixture (45%) from 5 following the
same procedure described for compound 4. Date for 7-a:
1H
NMR (CDCl3) d: 2.15 (s, 3H, CH3), 2.70–2.93 (m, 2H, H-10a,b), 3.91
(s, 1H, H-2), 3.96 (s, 1H, H-3), 4.37 (d, J = 11.6 Hz, 1H, CH2Ph),
4.44–4.68 (m, 5H, H-1, 4, 1.5 ꢀ CH2Ph), 7.06–7.20 (m, 2H, H-5, H-
1. Experimental
1.1. General methods
13
6), 7.26–7.40 (m, 10H, 2 ꢀ Ph); C NMR (CDCl3) d: 30.6 (C-30),
1H and 13C NMR spectra were recorded at 400 MHz and
100 MHz, respectively, with a Varian instrument at 293 K. Chemi-
cal shifts were given in ppm downfield to the signal of internal
46.5 (C-10), 71.9 (CH2Ph), 72.6 (CH2Ph), 79.7 (C-1), 79.7 (C-4),
85.8 (C-2), 87.1 (C-3), 127.7-128.8 (Ph), 136.8 (Ph), 137.4 (Ph),
139.8 (C-6), 139.1(C-6), 139.9 (C-5), 206.1 (C-20). Data for 7-b: 1H
NMR (CDCl3) d: 2.16 (s, 3H, CH3), 2.70–2.93 (m, 2H, H-10a, 10b),
3.87 (m, 1H, H-3), 4.08 (d, J = 3.6 Hz, 1H, H-2), 4.37 (d,
J = 11.6 Hz, 1H, CH2Ph), 4.44–4.68 (m, 5H, H-1, H-4, CH2Ph),
7.06–7.20 (m, 2H, H-5, H-6), 7.26–7.40 (m, 10H, 2 ꢀ Ph); 13C
NMR (CDCl3) d: 30.5 (C-30), 42.7 (C-10), 72.3 (CH2Ph), 72.2 (CH2Ph),
78.1 (C-1), 79.9 (C-4), 82.5 (C-2), 86.1(C-3), 127.7-128.8 (Ph), 136.8
(Ph), 137.4 (Ph), 139.4 (C-6), 139.7 (C-5), 206.3 (C-20). HRMS: calcd
for C23H26NO6 (M+H) 412.1760, found 412.1768.
TMS, and were assigned on the basis of 2D 1H-COSY and 1H–13
C
chemical-shift correlated experiments. To maintain consistency
in NMR assignments, carbon and proton numberings of the sugar
were used despite the compounds being named otherwise. For
high resolution mass spectroscopic analysis, samples in CH2Cl2–
MeOH, 1:1 were mixed with Agilent ES tuning mix for internal
mass calibration and infused into an AB/MDS-Sciex (Concord,
ON) QSTAR mass spectrometer at a flow-rate of 4 lL/min. All
chemicals were purchased from Aldrich Co. and used without fur-
ther purification.
1.2.2.3. 4-(1-C-Allyl-2,3-di-O-benzyl-
2H-1,2,3-triazole (8). A syrup with [
a
-
a
D
-erythrofuranoside-4s)-
]
+39 (c 0.5, CHCl3); 1H
D
NMR (CDCl3) d: 2.56 (dd, 2H, 10-CH2, J = 6.8, 6.8 Hz), 4.09 (dd, 1H,
H-2, J = 4.0, 4.4 Hz), 4.25 (dt, 1H, H-1, J = 4.4, 6.8 Hz), 4.32 (dd,
1H, H-3, J = 4.0, 7.2 Hz), 4.55 and 4.61 (d and d, 1H each, CH2Ph,
J = 12.4 Hz), 4.62 and 4.89 (d and d, 1H each, CH2Ph, J = 11.6 Hz),
5.06 (br d, 1H, CH2@, J = 10.4 Hz), 5.12 (br d, 1H, CH2@,
J = 17.2 Hz), 5.26 (d, 1H, H-4, J = 6.8 Hz), 5.80 (m, 1H, –CH@),
7.29–7.38 (m, 10H, 2 ꢀ Ph), 7.59 (s, 1H, H-6); 13C NMR (CDCl3) d:
34.5 (C-10), 73.0 (CH2Ph), 73.8 (CH2Ph), 74.3 (C-4), 77.9 (C-2),
80.6 (C-1), 84.7 (C-3), 117.4 (CH2@), 127.9, 128.0, 128.1, 128.5,
128.6, 134.8 (–CH@), 137.7, 138.5. HRMS: calcd for C23H26N3O3
(M+H) 392.1976, found 392.1991.
1.2. General procedure
1.2.1. Method A
The nitroalkene (100 mg) and sodium azide (20 mg) in DMF
(2 mL) were stirred overnight at room temperature. The mixture
was diluted by the addition of water, and extracted with EtOAc.
The organic phase was dried and concentrated. Purification by col-
umn chromatography gave the triazole sugars.
1.2.2. Method B
A solution of the nitroalkene (100 mg) in DMF (1 mL) was
mixed at 80 °C with sodium azide (20 mg) in DMF (1 mL). The mix-
ture was stirred overnight at that temperature. Upon cooling, the
mixture was diluted by the addition of water, and extracted with
EtOAc. The organic phase was dried and concentrated. Purification
by column chromatography gave fused triazoles.
1.2.2.4. 4-(1-C-Acetylmethyl-2,3-di-O-benzyl-
anoside-4s)-2H-1,2,3-triazole (9). Obtained in 47% as a syrup.
+26 (c 0.9, CHCl3); 1H NMR (CDCl3) d: 2.07 (s, 3H, CH3), 2.85
a-D-erythrofur-
[a]
D
(dd, 1H, H-10a, J = 6.4, 17.2 Hz), 2.97 (dd, 1H, H-10b, J = 7.2,
17.2 Hz), 4.23 (dd, 1H, H-2, J = 4.4, 3.2 Hz), 4.28 (dd, 1H, H-3,
J = 4.4, 6.0 Hz), 4.43 and 4.81 (d and d, 1H each, CH2Ph,
J = 11.2 Hz), 4.53 and 4.60 (d and d, 1H each, CH2Ph, J = 12.0 Hz),
4.65 (m, 1H, H-1), 5.18 (d, 1H, H-4, J = 6.8 Hz), 7.29–7.38 (m,
1.2.2.1. 1-C-(2,3-Di-O-benzyl-6-C-nitro-6-deoxy-a-D-ribo-hex-
5-eno-furanosyl)acetone (4). To a solution of compound 1
(3.5 g, 8.46 mmol) and Hg(OAc)2 (1.6 g, 5.0 mmol) in acetone–
water (37.5 mL:5 mL) was added dropwise a solution of Jones
reagent (0.84 M, 21 mL) over 30 min. The dark greenish-brown
mixture was stirred for 1 h and then poured into water and
extracted with EtOAc. The combined organic solution was washed
with water, aq NaHCO3, and brine, dried and concentrated. Purifi-
cation by chromatography (hexane–EtOAc 2:1) yielded compound
3 (2.2 g, 60%) as a solid. To a solution of the compound 3 (2 g,
4.7 mmol) and TEA (1.4 mL, 9.8 mmol) at 0 °C in DCM (30 mL)
13
10H, 2 ꢀ Ph), 7.59 (s, 1H, H-6); C NMR (CDCl3) d: 30.9 (C-30),
44.2 (C-10), 73.1 (CH2Ph), 74.0 (CH2Ph), 74.5 (C-4), 76.4 (C-1),
78.1 (C-2), 84.2 (C-3), 128.0, 128.1, 128.2, 128.3, 128.6, 128.7,
137.7, 138.3, 207.8 (C-20). HRMS: calcd for C23H26N3O4 (M+H)
408.1923, found 408.1890.
1.2.2.5. 4-(1-C-Acetylmethyl-2,3-di-O-benzyl-
side-4r)-2H-1,2,3-triazole (10). Obtained as an anomeric mix-
ture ( :b 1:1) following method A (40%) and method B (65%) as a
syrup. 1H NMR (CDCl3) d: 2.16 and 2.17 (2s,
- and b-CH3), 2.75–
a/b-L-threofurano-
was added MeSO2Cl (435
the mixture was poured into cold 5% HCl and extracted with EtOAc.
lL, 5.6 mmol) dropwise. After 30 min,
a
a

W. Zou et al. / Carbohydrate Research 344 (2009) 1024–1027
1027
2.97 (m, 2H, 10-CH2), 3.96 and 4.14 (2m, 1H, H-2), 4.18 and 4.31
(2m, 1H, H-3), 4.33–4.62 (m, 5H, H-1, 2 ꢀ CH2Ph), 5.11 and 5.27
(2d, 1H, H-4), 7.29–7.38 (m, 10H, 2 ꢀ Ph), 7.60 and 7.65 (2s, 1H,
4-OH, J = 10.0 Hz), 3.17 (dd, 1H, H-100a, J = 8.8, 17.6 Hz), 3.28 (dd,
1H, H-10b, J = 4.0, 17.6 Hz), 3.98 (dd, 1H, H-3, J = 4.0, 5.6 Hz), 4.19
(dd, 1H, H-2, J = 2.8, 5.6 Hz), 4.58 and 4.64 (d and d, 1H each,
CH2Ph, J = 11.6 Hz), 4.75 and 4.80 (d and d, 1H each, CH2Ph,
J = 12.0 Hz), 5.04 (m, 1H, H-1), 5.09 (dd, 1H, H-4, J = 4.0, 10.0 Hz),
7.29–7.38 (m, 10H, 2 ꢀ Ph), 7.73 (s, 1H, H-6); 13C NMR (CDCl3) d:
30.3 (C-30), 46.3 (C-10), 55.4 (C-1), 62.2 (C-4), 72.8 (CH2Ph), 73.8
(CH2Ph), 74.3 (C-3), 77.9 (C-2), 128.3, 128.4, 128.8, 128.9, 129.1,
132.3 (C-6), 134.9 (C-5), 136.7, 137.5, 205.8 (C-20). HRMS: calcd
for C23H26N3O4 (M+H) 408.1923, found 408.1912.
13
H-6); C NMR (CDCl3) d: 30.8 and 30.9 (C-30), 43.1 and 46.7 (C-
10), 72.1, 72.18, 72.2, 72.5, 78.0, 78.1, 79.3, 83.2, 86.9, 87.2, 88.4,
128.0, 128.1, 128.2, 128.3, 128.7, 137.4, 137.5, 137.6, 206.7 and
206.8 (C-20).
1.2.2.6. 2-(1,2-trans-2-Nitrocyclohexyl)-1,2,3-triazolo-[4,5]-
cyclohexane (12). Obtained as a syrup. 1H NMR (CDCl3) d: 1.45–
1.53 (m, 2H, H-4ax, 5ax), 1.81 (br s, 4H, 2 ꢀ N@C–CH2CH2), 1.80–
2.03 (m, 4H, H-3ax, 6ax, 4eq, 5eq), 2.26 (dm, 1H, H-6eq), 2.50
(dm, 1H, H-3eq), 2.66 (br s, 4H, 2 ꢀ N@C–CH2), 4.99 (ddd, 1H, H-
2, J = 4.0, 11.2, 11.2 Hz), 5.15 (ddd, 1H, H-1, J = 4.0, 11.2, 11.2 Hz);
13C NMR (CDCl3) d: 21.9 (2 ꢀ N@C–CH2CH2), 23.2 (2 ꢀ N@C–
CH2CH2), 24.0 (C-4), 24.2 (C-5), 31.8 (C-6), 32.0 (C-3), 64.4 (C-1),
87.8 (C-2), 144.4 (2 ꢀ N@C–CH2CH2); MS: m/z 251.4 (M+H),
268.3 (M+NH4).
Acknowledgements
This is NRC-CNRC publication No. 42532. We thank Ken Chan
and Jacek Stupak for MS analysis and Nam Khieu for the assistance
in NMR 0.analysis.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2009.03.007.
1.2.2.7. (3r,4s,5s,6s)-6-Acetylmethyl-4,5-di-O-benzyl-3-hydroxy-
pyrido[1,5-c]-1,2,3-triazole (14). Obtained from 4 in 47% as a
syrup. [
a
]
D ꢁ21 (c 1.5, CHCl3); 1H NMR (CDCl3) d: 2.12 (s, 3H, CH3),
3.07 (d, 1H, 4-OH, J = 12.0 Hz), 3.12 (dd, 1H, H-10a, J = 4.0, 17.6 Hz),
3.28 (dd, 1H, H-10b, J = 6.0, 17.6 Hz), 4.12 (d, 1H, H-2, J = 8.4 Hz);
4.15 (d, 1H, H-3, J = 4.0 Hz), 4.62 and 4.77 (d and d, 1H each, CH2Ph,
J = 11.6 Hz), 4.70 and 4.94 (d and d, 1H each, CH2Ph, J = 11.6 Hz), 4.87
(dd, 1H, H-4, J = 4.0, 12.0 Hz), 4.92 (m, 1H, H-1), 7.29–7.38 (m, 10H,
References
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13
2 ꢀ Ph), 7.69 (s, 1H, H-6); C NMR (CDCl3) d: 30.9 (C-30), 42.6
(C-10), 54.0 (C-1), 63.3 (C-4), 72.8 (CH2Ph), 73.9 (C-3), 74.1 (CH2Ph),
77.2 (C-2), 128.3, 128.4, 128.5, 128.7, 128.9, 129.0, 132.6 (C-6),
136.0 (C-5), 136.8, 137.4, 205.2 (C-20). HRMS: calcd for C23H26N3O4
(M+H) 408.1923, found 408.1919.
1.2.2.8. (3s,4r,5s,6r)-6-Acetylmethyl-4,5-di-O-benzyl-3-hydroxy-
pyrido[1,5-c]-1,2,3-triazole (15). Major product (23%) obtained
from 7 as a syrup. [a]
+63 (c 1.0, CHCl3); 1H NMR (CDCl3) d: 2.15
D
(s, 3H, CH3), 2.81 (d, 1H, 3-OH, J = 11.2 Hz), 3.04 (dd, 1H, H-10a,
J = 9.6, 18.4 Hz), 3.82 (dd, 1H, H-10b, J = 4.0, 18.4 Hz), 4.02 (dd,
1H, H-3, J = 4.4, 4.4 Hz), 4.30 (dd, 1H, H-2, J = 3.6, 4.4 Hz), 4.38
and 4.51 (d and d, 1H each, CH2Ph, J = 11.6 Hz), 4.61 and 4.70 (d
and d, 1H each, CH2Ph, J = 11.6 Hz), 4.97 (m, 1H, H-1), 5.01 (dd,
1H, H-4, J = 4.0, 11.2 Hz), 7.29-7.38 (m, 10H, 2 ꢀ Ph), 7.72 (s, 1H,
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11. Zou, W.; Wu, A.-T.; Bhasin, M.; Sandbhor, M.; Wu, S.-H. J. Org. Chem. 2007, 72,
2686–2689.
13
H-6); C NMR (CDCl3) d: 30.5 (C-30), 41.9 (C-10), 52.8 (C-1), 63.0
(C-4), 73.6 (C-2, 3), 73.7 (CH2Ph), 73.8 (CH2Ph), 128.5, 128.6,
128.8, 128.9, 129.0, 132.6 (C-6), 136.0 (C-5), 136.7, 136.8, 205.9
(C-20). HRMS: calcd for C23H26N3O4 (M + H) 408.1923, found
408.1944.
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4726–4734.
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254–256.
1.2.2.9. (3s,4r,5s,6s)-6-Acetylmethyl-4,5-di-O-benzyl-3-hydroxy-
pyrido[1,5-c]-1,2,3-triazole (16). Minor product (10%) obtained
from 7 as a syrup. 1H NMR (CDCl3) d: 2.10 (s, 3H, CH3), 2.79 (d, 1H,
14. Zou, W.; Sandbhor, M.; Bhasin, M. J. Org. Chem. 2007, 72, 1226–1234.