Synthesis and biological evaluation of glycal-derived novel tetrahydrofuran 1,2,3-triazoles by 'click' chemistry

Article abstract of DOI:10.1016/j.carres.2010.03.031

Thirteen new 1,2,3-triazoles (5a-e, 15a-d, 17a-b, 19, and 21) were synthesized by 'click' reaction of sugar-derived azides with commercially available acetylenes. The synthesized triazoles were tested in vitro for their biological activity, and compound 5

Full text of DOI:10.1016/j.carres.2010.03.031

Carbohydrate Research 345 (2010) 1515–1521
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis and biological evaluation of glycal-derived novel tetrahydrofuran
1,2,3-triazoles by ‘click’ chemistry q
L. Vijaya Raghava Reddy a, P. Venkat Reddy a, Nripendra N. Mishra b, Praveen K. Shukla b, Garima Yadav c,
Ranjana Srivastava c, Arun K. Shaw a,
*
a Division of Medicinal and Process Chemistry, Central Drug Research Institute (CSIR), Lucknow 226 001, India
b Division of Fermentation Technology, Central Drug Research Institute (CSIR), Lucknow 226 001, India
c Division of Microbiology, Central Drug Research Institute (CSIR), Lucknow 226 001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Thirteen new 1,2,3-triazoles (5a–e, 15a–d, 17a–b, 19, and 21) were synthesized by ‘click’ reaction of
sugar-derived azides with commercially available acetylenes. The synthesized triazoles were tested
in vitro for their biological activity, and compound 5b displayed both antibacterial and antifungal activ-
Received 20 January 2010
Received in revised form 20 March 2010
Accepted 24 March 2010
ities at an MIC value of 12.5
value of 25 g/mL.
l
g/mL, while compounds 15b and 19 showed antibacterial activity at an MIC
Available online 30 March 2010
l
Ó 2010 Elsevier Ltd. All rights reserved.
Dedicated to Professor Manas Chakrabarty
on the occasion of his 62nd birthday
Keywords:
1,2,3-Triazoles
Click chemistry
THF domain
1. Introduction
anticonvulsant,27 antiinflammatory, local anesthetic,28 antimalar-
ial,29 antiviral,30 and antimycobacterial agents.31,32 Additionally
some 1,2,3-triazoles are even used as b3-selective adrenergic recep-
tor antagonists,33 potassium channel activators,34 and DNA cleaving
agents.35
In the field of pharmaceutical sciences, ‘click’ chemistry serves
as a guiding principle in the quest for leads in drug discovery. It
is a modular approach that uses only the most practical and reli-
able chemical transformations in modern-day chemistry.1,2 Of
the various ‘click’ reactions that are available to us, the Cu(I)-cata-
lyzed Huisgen 1,3-dipolar cycloaddition of azides and acetylenes to
give 1,2,3-triazoles3–7 has gained a significant amount of attention
by researchers as its applications are increasingly found in all as-
pects of drug discovery ranging from lead finding through combi-
natorial chemistry,8,9 target-templated in situ chemistry,10–13 to
tagging of biological systems, such as proteins, nucleotides, and
whole organisms using bioconjugation reactions.14–17
Amongst various classes of nitrogen heterocycles, 1,2,3-triazoles
and their derivatives deserve special recognition due to their wide
usage in industrialapplicationsas dyes, photographic materials, cor-
rosion inhibitors, and agrochemicals such as herbicides, fungicides,
and antibacterial agents.18,19 Several members of the 1,2,3-triazole
family indeed are found to exhibit a broad spectrum of biological
activities such as antimicrobial,20,21 anti-HIV,22–24 antiallergic,25,26
The importance of the triazole core lies in the fact that they can-
not be cleaved hydrolytically and are almost impossible to oxidize
or reduce. Though 1,2,3-triazole units are not present in natural
products, they are remarkably stable to metabolic transformations
and are seen in many drugs such as tazobactam and cefatrizine.36
1,2,3-Triazoles may act as H-bond donors or acceptors, depending
on their substitution. In 1,4-disubstituted 1,2,3-triazoles, N-2 and
N-3 act as H-bond acceptors. The strong dipole moment of triazole
polarizes H–C-5 to a degree that it may function as a weak H-bond
donor.37 Recent studies on 1,2,3-triazoles revealed that the hydro-
gen bonding and dipole interactions of the triazole core can favor
their binding to biomolecular targets and improve their solubil-
ity.38,39 As we were interested by the wide variety of pharmacolog-
ical properties and potential applications of 1,2,3-triazoles, we
designed the synthesis of a small library of stereo-diversified enan-
tiopure tetrahydrofuran 1,2,3-triazole molecules of prototypes I
and II (Fig. 1) as the tetrahydrofuran backbone is found in several
molecules of biological importance.40–46 In both the series we
decided to retain the benzyl protection group in the final molecules
as it is lipophilic in nature and is reported to influence the biolog-
ical activity profile in a positive manner.47,48
q
CDRI Communication No. 7659.
* Corresponding author. Tel.: +91 9415403775.
E-mail address: akshaw55@yahoo.com (A.K. Shaw).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.03.031

1516
L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
in 4–8 h (Scheme 1). Their structures were established by their
1H NMR, 13C NMR, and IR spectroscopic and high-resolution mass
spectrometric analyses.
O
O
O
O
N
To observe the role of stereoselectivity on biological activity
profile of the triazoles, we tried to synthesize azide 9 (Scheme 2),
whose stereochemistry at the C-2 position of the THF ring was dif-
ferent. Treatment of the diol 7 (Rf 0.90, 1:1 EtOAc–hexane) ob-
tained from our previously reported THF domain 6,49 with I2,
PPh3, imidazole in toluene at 40–45 °C showed the formation of a
single product at Rf 0.41 (3:7 EtOAc–hexane). It was then subjected
to azide displacement with NaN3 in DMF at 50–60 °C for 12 h. But
the TLC analysis of the reaction mixture did not show any change
in Rf value (0.41) or color even after 12 h of reaction time. After the
usual workup, the reaction mixture was purified by column chro-
matography, and to our surprise characterization of the pure col-
umn product obtained on iodination of the diol 7 (50% yield)
revealed that the compound formed was not the deoxyiodo deriv-
ative 8, as no peak was observed corresponding to the methylene
carbon attached to the iodide around the range of 10 ppm or less.
Careful examination of the spectroscopic data and consideration of
a few literature precedents50–52 identified it as dioxabicyclo com-
pound 10 formed by the cyclization of the hydroxyl deoxyiodo
intermediate under basic reaction conditions (Scheme 2). It is
worth mentioning here that although the hydroxymethyl at C-2
and the hydroxyl functionality at C-4 are also placed syn to each
other in compound 3, iodination of 3 did not yield any bicyclo com-
pound as the C-3-OBn is placed anti to both C-2 and C-4. Probably,
the syn orientation of C-3-OBn with respect to C-2 and C4 in com-
pound 7 could have favored the formation of the 10. To the best of
our knowledge this is the first report of this kind of cyclization un-
der mild reaction conditions, while the previous instances required
the use of strong external sources like potassium tert-butoxide,50
NaH,51 or palladium(II) catalyst.52
N
N
OBn
N
N
HO
OBn
R
N
R
Prototype I
Prototype II
Figure 1. Prototype molecules.
2. Results and discussion
The synthesis of 1,4-disubstituted-1,2,3-triazoles of prototype I
was undertaken with a view that the methylenic spacer between
the two heterocyclic rings can bring a free rotation in the molecule,
and the free hydroxyl group will act as a neutral hydrogen-bond
donor that can facilitate proper binding to biomolecular target(s).
To begin with, the precursor THF domain 2, easily prepared in
three steps starting from 3,4,6-tri-O-benzyl-D-galactal (1) follow-
ing our previous procedure,49 was subjected to sequential hydroly-
sis and oxidation with H5IO6, followed by immediate reduction of
the resulting aldehyde by NaBH4 to afford diol 3 (Scheme 1). The
diol thus obtained was transformed to azide 4 via the deoxyiodo
intermediate. The IR spectrum of
4 showed absorption at
2106 cmꢀ1, which is characteristic of the azido functionality, while
its FABMS displayed peak at m/z 207 corresponding to [MꢀN3]+Å.
The 13C NMR spectrum displayed peak at 53.2 ppm corresponding
to a methylene carbon attached to an azido function, confirming
the formation of the azidodeoxy compound.
Treatment of azide 4 with phenylacetylene at ambient temper-
ature in the presence of CuSO4ꢁ5H2O, sodium ascorbate and 1:1 t-
BuOH–H2O furnished the triazole 5a as a single isomer (Scheme 1).
The 1H NMR spectrum of 5a showed a singlet at d 7.90 correspond-
ing to the triazolyl proton, while the 13C NMR spectrum showed
peaks at d 121.5 and 148.2 corresponding to CH and qC character-
istic to the triazole core unit. The ESIMS displayed an [M+H]+Å peak
at m/z 352, while its HRESIMS showed an [M]+ peak, thus confirm-
ing its structure. Similarly, treatment of the above-mentioned
azide 4 with different alkynes viz. 1-decyne, 2-ethynylpyridine,
5-chloropent-1-yne, and 5-ethynyl-1-methyl-1H-imidazole led to
the formation of their respective triazoles 5b–e in 40–78% yields
Next, we turned our attention to the synthesis of the triazole
derivatives with opposite stereochemical configurations at C-2
and C-3 of the THF ring to that of triazoles 5a–5e. In this endeavor
the diol 13 was prepared by subjecting the THF domain 12,49 pre-
pared from 3,4,6-tri-O-benzyl-D-glucal, to a sequential oxidative
cleavage and reduction by H5IO6 and NaBH4, respectively. The diol
13 in a standard iodination reaction followed by treatment with
excess of sodium azide, furnished the diastereomerically pure
azide 14. Subsequent treatment of the azide 14 with different al-
kynes, viz., phenylacetylene, decyne, 2-ethynylpyridine, and chlor-
opentyne, under Huisgen 1,3-dipolar cycloaddition reaction
conditions furnished their corresponding 1,2,3-triazoles 15a–d in
good yields (Scheme 3).
O
BnO
BnO
OBn
O
O
OH
O
i, ii
three
steps
O
OBn
O
O
HO
OH
i, ii
three
steps
HO
OBn
O
1
3
O
1
2
HO
OBn
OBn
HO
6
7
N
O
O
N
R
N
v
O
iii, iv
N3
N3
HO
OBn
HO
OBn
HO
O
OBn
4
5a R = phenyl (86%)
5b R = n-octyl (78%)
5c R = 2-pyridyl (64%)
5d R = 3-chloropropyl (75%)
5e R = 1-methyl-1H-
9
I
iii
BnO
HO
OBn
8
O
O
imidazol-5-yl (41%)
10
Scheme 1. Reagents and conditions: (i) H5IO6 (1.3 equiv), EtOAc, rt, 3 h; (ii) NaBH4,
EtOH, 0 °C–rt 2.5 h (76% for two steps); (iii) I2 (1.5 equiv), PPh3 (1.5 equiv),
imidazole (3.0 equiv), toluene, 40–45 °C, 1.5 h; (iv) NaN3 (10 equiv) DMF, 50–60 °C,
Scheme 2. Reagents and conditions: (i) H5IO6 (1.3 equiv), EtOAc, rt, 3 h; (ii) NaBH4,
EtOH, 0 °C–rt 2.5 h (72% for two steps); (iii) I2 (1.5 equiv), PPh3 (1.5 equiv),
imidazole (3.0 equiv), toluene, 40–45 °C, 1.5 h; (iv) NaN3 (10 equiv) DMF, 50–60 °C,
>12 h (50% from 8).
3 h (42% yield for two steps); (v)
, CuSO ꢁ5H O (0.2 equiv), sodium
H
R
4
2
ascorbate (0.4 equiv), t-BuOH–H2O (1:1), rt, 4–8 h.

L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
1517
O
O
O
O
OBn
O
O
O
O
2-Ethynylpyridine (1.2 equiv),
O
O
O
i, ii
OH
.
CuSO4 5H2O (0.2 equiv),
three
steps
BnO
BnO
HO
HO
N
N
OBn
OBn
N3
OBn
OBn
sodium ascorbate (0.4 equiv),
11
12
13
N
18
1:1 t-BuOH−H2O, rt, 5−6h
N
O
N
O
N
N
R
N3
v
iii, iv
19 (94%)
HO
OBn
15a R = phenyl (67
15b R = n-octyl (64
15c R = 2-pyridyl (77
HO
OBn
14
%)
%
)
%)
O
O
2-Ethynylpyridine (1.2 equiv),
15d R =3 -chloropropyl (53
%)
.
O CuSO4 5H2O (0.2 equiv),
O
O
OBn
O
OBn
Scheme 3. Reagents and conditions: (i) H5IO6 (1.3 equiv), EtOAc, 3 h; (ii) NaBH4,
EtOH, 0 °C–rt 2.5 h (76% for two steps); (iii) I2 (1.5 equiv), PPh3 (1.5 equiv),
imidazole (3.0 equiv), toluene, 40–45 °C, 1.5 h; (iv) NaN3 (10 equiv) DMF, 50–60 °C,
3 h (44% for two steps); (v)
(0.4 equiv), 1:1 t-BuOH–H2O, rt, 5–6 h.
N3
N
N
N
sodium ascorbate (0.4 equiv),
20
1:1 t-BuOH−H2O, rt, 5−6h
N
, CuSO ꢁ5H O (0.2 equiv), sodium ascorbate
H
R
4
2
21 (94%)
Finally, we were also interested in studying the biological activ-
ity of prototype II triazole derivatives, in which the triazole ring is
placed at the C-4 position of the THF ring with varied stereochem-
istries at C-2 and C-3. Thus, the triazoles 17a–b (85% for 17a, 54%
for 17b), 19 (94%), and 21 (94%) were synthesized from their
respective azides 16,53 18,54 and 2054 (Scheme 4 and Scheme 5).
All these synthesized triazoles were found to be >99% pure as
shown by their NMR spectra and HRESIMS.
Scheme 5. Synthesis of triazoles 19 and 21.
phobicity of the side chain, an observation in agreement with the
previous literature reports.31,32,55
3. Conclusions
The synthesized triazole derivatives of both prototypes I and II
were tested in vitro for their antifungal activity against Candida
albicans, Cryptococcus neoformans, Sporothrix schenckii, Trichophy-
ton mentagrophytes, Aspergillus fumigatus, Candida parapsilosis and
for antibacterial activity against Escherichia coli, Pseudomonas aeru-
ginosa, Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium
tuberculosis H37Rv.
In conclusion, a convenient route to synthesize a small ensem-
ble of novel tetrahydrofurans, 1,2,3-triazole derivatives with differ-
ent stereochemical patterns is illustrated. The above-mentioned
results conclude that the relative stereochemistries of the substit-
uents of synthesized 1,2,3-triazoles had a very little effect on their
activity profile. However, appropriate modification/optimization of
the above-synthesized triazoles may generate more promising
molecules having pronounced biological activities, which is cur-
rently in progress in our laboratory.
Out of all the tested compounds, only three compounds showed
activity at 50
octyl triazole 5b (prototype I) was able to inhibit the growth of S.
aureus at a concentration of 12.5 g/mL, which is comparable to
the antibacterial drug gentamycin (MIC value of 6.25 g/mL). The
same compound also showed growth inhibition of S. schenckii
and K. pneumoniae at concentrations of 12.5 and 25 g/mL, respec-
lg/mL (Minimal Inhibitory Concentration, MIC). The
l
4. Experimental
l
4.1. Biological evaluation procedures
l
tively. Among the other triazole derivatives, octyl triazole 15b,
whose stereochemistries at C-2 and C-3 of the tetrahydrofuran
core unit were opposite to those of 5b, and pyridyl triazole 19
exhibited very mild in vitro antibacterial activity at an MIC of
4.1.1. Radiometric method for drug susceptibility testing using
BACTEC 460 TB systems (Becton Dickinson)
A total of 104–105 CFU/mL (CFU = Colony forming units) of M.
tuberculosis H37Rv was inoculated in 4 mL of fresh BACTEC 12B
broth containing the test compounds. An additional control was
inoculated with 1:100 dilution of the inoculum to represent 1%
of the bacterial population (102+–103+ CFU/mL). The vials were
incubated at 37 °C, and GI (Growth Index) readings were recorded
daily until the GI 1:100 control had reached 30. The concentration
of the drug producing a final GI reading lower than those in the
1:100 control was considered to have inhibited more than 90% of
the bacteria and was defined as the MIC (Minimal Inhibitory
Concentration).
25 lg/mL against K. pneumoniae and S. aureus, respectively. Lack
of potent antibacterial and antifungal activity of phenyl triazoles
(5a, 15a, and 17a) and chloropropyl triazoles (5d and 15d) rein-
states that biological activity was largely dependent on the hydro-
O
(1.2 equiv),
O
R
H
O
O
O
O
.
CuSO4 5H2O (0.2 equiv),
4.1.2. In vitro antifungal and antibacterial activity evaluation
All the prepared 1,4-disubstituted-1,2,3-triazoles were evalu-
ated for their in vitro antifungal activity against C. albicans, C. neofor-
mans, S. schenckii, T. mentagrophytes, A. fumigatus, and C. parapsilosis
(ATCC 22019) and antibacterial activity against E. coli, P. aeruginosa
(ATCC BAA-427), S. aureus (ATCC 25923), and K. pneumoniae (ATCC
27736). In this process, the minimum inhibitory concentration of
compounds was tested according to the standard microbroth
sodium ascorbate (0.4 equiv),
N3
OBn
N
N
OBn
1:1 t-BuOH−H2O, rt, 5−6h
N
16
R
17a R = Ph (85%)
17b R = CH2OH (54%)
Scheme 4. Synthesis of triazoles 17a and 17b.

1518
L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
dilution technique as per NCCLS guidelines.56 Briefly, testing was
performed in flat-bottomed 96-well tissue culture plates (CELL-
STARÒ Greiner bio-one GmbH, Germany) in RPMI 1640 medium buf-
fered with MOPS (3-[N-morpholino]propanesulfonic acid) (Sigma–
Aldrich Chemical Co., St. Louis, MO, USA) for fungal strains and in
Muller Hinton broth (Titan Biotech Ltd, India) for bacterial strains.
The concentration range of test compounds was 50–0.36 and 32–
136, 91. DART-HRESIMS: calcd for C12H17O4 (M+H)+ 225.1126;
found m/z 225.1127.
4.3.2. 2,5-Anhydro-3-O-benzyl-4-deoxy-4-methyl-D-arabinitol
(7)
Yield: 322 mg (72% from 6), oil. Eluent for column chromatogra-
phy: 2:3 EtOAc–hexane, ½a D28
ꢃ
ꢀ50.7 (c 0.10, CHCl3), Rf 0.12 (2:3
0.0018
l
g/mL for standard compounds. Initial inocula of fungal
EtOAc–hexane). IR (neat): m 3420 (–OH str), 3020 (@CH str),
and bacterial strains were maintained at 1–5 ꢂ 103 cells/mL. These
plates were incubated in a moist chamber at 35 °C, and an absor-
bance at 492 nm was recorded on a VersaMax microplate reader
(Molecular devices, Sunnyvale, USA) after 48 h for C. albicans and
C. parapsilosis, 72 h for A. fumigatus, S. schenckii, and C. neoformans,
and 96 h for T. mentagrophytes, while bacterial strains were incu-
bated for 24 h. The MICs were determined as 90% inhibition of
growth with respect to the growth control as observed using SOFT-
max Pro 4.3 Software (Molecular Devices, Sunnyvale, USA).
2925, 2361, 1633, 1521, 1455, 1216 cmꢀ1 1H NMR (300 MHz,
.
CDCl3): d 3.68–3.83 (m, 3H), 3.93 (d, 1H, J = 9.8 Hz), 4.03–4.06
(m, 1H), 4.18–4.22 (m, 2H), 4.53, 4.76 (2 d, 2H, J = 11.5 Hz, CH2Ph),
7.30–7.34 (m, 5H, ArH). 13C NMR (75 MHz, CDCl3 + CCl4): d 61.6
(CH2), 69.8 (CH), 73.1 (CH2), 73.8 (CH2), 78.8 (CH), 79.6 (CH),
128.2 (ArC), 128.5 (ArC), 129.0 (ArC), 137.7 (ArCq). DART-HRESIMS:
calcd for C12H17O4 (M+H)+ 225.1126; found m/z 225.1140.
4.3.3. 2,5-Anhydro-3-O-benzyl-D-ribitol (13)
Yield: 340 mg (76% from 12), oil. Eluent for column chromatog-
4.2. General methods and materials
raphy: 7:13 EtOAc–hexane, ½a D28
ꢀ45.8 (c 0.33, CHCl3), Rf 0.86 (1:1
ꢃ
EtOAc–hexane). IR (neat):
m 3419 (–OH str), 3019 (@C–H str), 1599,
All the products were characterized by 1H, 13C, IR, FABMS, DART
(Direct Analysis in Real Time)-HRESIMS, ESIMS and HREIMS (C, H,
O). Analytical TLC was performed using 2.5 ꢂ 5 cm plates coated
with a 0.25 mm thickness of silica gel (60F-254), and visualization
was accomplished with CeSO4 (1% in 2.0 N H2SO4), or in some cases
30% (v/v) H2SO4 in MeOH and subsequent charring over the hot
plate. 1H NMR spectra were recorded at 300 MHz with TMS as
the internal reference. 13C NMR spectra were recorded at 75 MHz
with CDCl3 as the internal reference. Chemical shifts are given in
parts per million downfield from the internal standard Me4Si.
Yields refer to pure compounds after chromatography unless
otherwise mentioned. IR spectra were recorded on Perkin–Elmer
881 and FTIR-8210 PC Shimadzu spectrophotometers. Mass spec-
tra were recorded on a JEOL JMS-600H high-resolution spectrome-
ter in the EI mode at 70 eV. Optical rotations were determined on
an Autopol III polarimeter using a 1-dm cell at 28 °C in CHCl3–
MeOH as the solvent; concentrations mentioned are in g/100 mL.
1216 cmꢀ1 1H NMR (300 MHz, CDCl3): d 2.08 (br s, 1H, –OH), 2.65
.
(br s, 1H, –OH), 3.51 (dd, 1H, J = 3.2, 12.0 Hz), 3.74–3.80 (m, 2H),
3.85–4.00 (m, 3H), 4.14–4.15 (m, 1H), 4.61 (s, 2H, CH2Ph), 7.25–
7.37 (m, 5H, ArH). 13C NMR (75 MHz, CDCl3 + CCl4): d 62.4 (CH2),
70.3 (CH), 73.4 (CH2), 74.0 (CH2), 79.2 (CH), 81.2 (CH), 128.4
(ArC), 128.8 (ArC), 129.1 (ArC), 137.6 (ArCq). FABMS: m/z 224;
found 207 (MꢀOH)+, 154, 136, 91. DART-HRESIMS): calcd for
C
12H17O4 (M+H)+ 225.1126; found m/z 225.1108.
4.4. General procedure for the preparation of azides
To a solution of pure diol (448 mg, 2.0 mmol) in toluene at 40–
45 °C were added, with vigorous stirring, iodine (598 mg,
1.5 equiv), triphenylphospine (786 mg, 1.5 equiv), and imidazole
(484 mg, 3.0 equiv). After completion of the reaction, the reaction
mixture was decolorized by shaking it with aq Na2S2O3, and the
aqueous layer was extracted thrice with EtOAc. The combined or-
ganic layer was dried over anhyd Na2SO4, and evaporated to
dryness.
4.3. General procedure for the preparation of diol
To a solution of the crude deoxyiodo intermediate in DMF
(5 mL) at 50–60 °C was added excess of NaN3 (1.31 g, 10 equiv),
and the mixture was allowed to stir at the same temperature until
the completion of reaction. The reaction mixture was then diluted
with an excess of water and extracted with EtOAc (4 ꢂ 15 mL). The
combined organic layer obtained was evaporated under high vac-
uum and subjected to column chromatography to yield the pure
azide.
A solution of the THF domain (588 mg, 2.0 mmol) and periodic
acid (592 mg, 1.3 equiv) in 10 mL of dry EtOAc was allowed to stir
at room temperature for 3 h. After the completion of the reaction
(TLC), the reaction was quenched with satd aq NaHCO3, and the
mixture was extracted with EtOAc (3 ꢂ 15 mL). The combined or-
ganic layer was dried over anhyd Na2SO4 and evaporated under re-
duced pressure to afford the aldehyde that was immediately
utilized for the next reaction step.
To a precooled solution of the crude aldehyde (445 mg) in
EtOH was added NaBH4 (38 mg, 0.5 equiv), and the mixture
was left stirring for 2.5 h. After the completion of reaction, excess
of NaBH4 was quenched with acetone, and the whole organic
layer was evaporated and column-chromatographed to furnish
the pure diol.
4.4.1. 1,4-Anhydro-5-azido-3-O-benzyl-2,5-dideoxy-2-methyl-D-
arabinitol (4)
Yield: 158 mg (42% from 3), oil. Eluent for column chromatogra-
phy: 13:77 EtOAc–hexane, ½a D28
ꢃ
+47.9 (c 0.19, CHCl3), Rf 0.54 (3:7
m 3447 (–OH str), 3019 (@C–H str),
EtOAc–hexane). IR (neat):
2106 (–N3 str), 1216 cmꢀ1 1H NMR (300 MHz, CDCl3): d 2.43 (d,
.
1H, J = 6.5 Hz, –OH), 3.44 (dd, 1H, J = 4.4, 12.7 Hz), 3.55 (dd, 1H,
J = 4.0, 12.7 Hz), 3.77–3.78 (m, 1H), 3.87–3.97 (m, 3H), 4.24 (br s,
1H), 4.57, 4.65 (2 d, 2H, J = 12.0 Hz, CH2Ph), 7.28–7.36 (m, 5H,
ArH). 13C NMR (75 MHz, CDCl3 + CCl4): d 53.2 (–CH2N), 72.5
(CH2), 75.0 (CH), 75.9 (CH2), 83.1 (CH), 87.3 (CH), 128.1 (ArC),
128.4 (ArC), 129.0 (ArC), 137.9 (ArCq). FABMS: m/z 249; found
207 (MꢀN3)+, 147, 136, 91. DART-HRESIMS: calcd for C12H16N1O3
(M+1ꢀN2) 222.1130; found m/z 222.1141.
4.3.1. 1,4-Anhydro-2-deoxy-2-methyl-3-O-phenyl-D-arabinitol
(3)
Yield: 340 mg (76% from 2), oil. Eluent for column chromatogra-
phy: 9:16 EtOAc–hexane, ½a D28
ꢃ
+18.4 (c 0.25, CHCl3), Rf 0.16 (1:1
3364 (–OH str), 2922 (@CH str),
.
1H NMR (300 MHz, CDCl3): d 3.61
EtOAc–hexane). IR (neat):
m
2361, 1650, 1454, 1050 cmꢀ1
(dd, 1H, J = 2.0, 11.7 Hz), 3.78–3.95 (m, 5 H), 4.16 (br s, 1H), 4.53,
4.62 (2 d, J = 11.9 Hz, 2H, CH2Ph), 7.23–7.32 (m, 5H, ArH). 13C
NMR (75 MHz, CDCl3 + CCl4): d 62.9 (CH2), 72.3 (CH2), 75.0 (CH),
75.3 (CH2), 85.1 (CH), 86.8 (CH), 128.0 (ArC), 128.3 (ArC), 128.9
(ArC), 138.1 (ArCq). FABMS: m/z 224; found 225 [M+H]+Å, 154,
4.4.2. 1,4:2,5-Dianhydro-3-deoxy-3-ethylpentitol (10)
Yield: 206 mg (50%), oil. Eluent for column chromatography:
3:22 EtOAc–hexane, ½a D28
ꢃ
+46.0 (c 0.53, CHCl3), Rf 0.41 (3:7

L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
1519
EtOAc–hexane). 1H NMR (300 MHz, CDCl3): d 3.84–3.95 (m, 3H),
4.05–4.12 (m, 3H), 4.22 (br s, 1H), 4.55, 4.65 (2 d, 2H, J = 11.8 Hz,
CH2Ph), 7.25–7.33 (m, 5H, ArH). 13C NMR (75 MHz, CDCl3 + CCl4):
d 72.5 (CH2), 73.2 (CH2), 74.2 (CH2), 76.0 (CH), 76.3 (CH), 80.2
(CH), 128.2 (ArC), 128.4 (ArC), 128.9 (ArC), 137.9 (ArCq). FABMS:
m/z 206; found 207 (M+H)+Å HRESIMS: calcd for C12H15O3 (M+H)+
207.10212; found m/z 207.10173.
128.1 (ArC), 128.3 (ArC), 128.9 (ArC), 137.7 (ArCq), 148.8 (Cq of tri-
azole). ESIMS: m/z 387; found 388 (M+H)+Å DART-HRESIMS: calcd
for C22H34N3O3 (M+H)+ 388.2600; found m/z 388.2567.
4.5.3. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-[4-
(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]-D-arabinitol (5c)
Yield: 113 mg (64%), solid, mp 98–100 °C, Eluent for column
chromatography: 3:97 MeOH–CHCl3, ½a D28
ꢃ
+42.5 (c 0.10, CHCl3),
3413 (–OH str), 3021
4.4.3. 2,5-Anhydro-1-azido-3-O-benzyl-1,4-dideoxy-4-methyl-
D
-
Rf 0.80 (1:19 MeOH–CHCl3). IR (KBr):
m
ribitol (14)
(@CH str), 2360, 1601, 1425 and 1216 cmꢀ1 1H NMR (300 MHz,
.
Yield: 166 mg (44% from 13), oil. Eluent for column chromatog-
CDCl3 + CCl4): d 3.74–3.75 (m, 1H), 3.87–3.91(m, 3H), 4.12–4.17
(m, 1H), 4.24 (s, 1H), 4.44–4.55 (m, 4H), 7.09–7.22 (m, 6H, ArH),
7.63–7.69 (m, 1H, ArH), 8.05 (d, 1H, J = 7.9 Hz), 8.24 (s, 1H, triazolyl
H), 8.40 (d, 1H, J = 4.3 Hz). 13C NMR (75 MHz, CDCl3 + CCl4): d 52.6
(CH2N), 72.3 (CH2), 75.0 (CH2), 75.7 (CH), 82.6 (CH), 86.9 (CH),
120.9 (CH of triazole), 123.1 (ArC), 124.2 (ArC), 128.1 (ArC), 128.3
(ArC), 128.9 (ArC), 137.5 (ArC), 137.8 (ArCq), 148.1 (Cq of triazole),
149.4 (ArC), 150.6 (ArCq). ESIMS: m/z 352; found 353 (M+H)+Å HRE-
IMS: calcd for C19H21N4O3 (M+H)+ 353.1614; found m/z 353.1612.
raphy: 3:22 EtOAc–hexane, ½a D28
ꢀ69.6 (c 0.12, CHCl3), Rf 0.43 (2:3
ꢃ
EtOAc–hexane). IR (neat):
m 3376 (–OH str), 3021 (@C–H str), 2361,
2105 (–N3 str), 1216 cmꢀ1. 1H NMR (200 MHz, CDCl3): d 2.53 (br s,
1H, –OH), 3.12 (dd, 1H, J = 3.7, 13.1 Hz,), 3.51(dd, 1H, J = 3.3,
13.1 Hz,), 3.78–4.07 (m, 4H), 4.17–4.19 (m, 1H), 4.58, 4.65 (2 d,
2H, J = 11.7 Hz, CH2Ph), 7.30–7.37 (m, 5H, ArH). 13C NMR
(75 MHz, CDCl3 + CCl4): d 52.3 (–CH2N), 70.1 (CH), 73.4 (CH2),
73.9 (CH2), 79.7 (CH), 80.2 (CH), 128.5 (ArC), 128.9 (ArC), 129.2
(ArC), 137.4 (ArCq). FABMS: m/z 249; found 207 (MꢀN3)+Å DART-
HRESIMS: calcd for C12H16NO3 (M+HꢀN2) 222.1130; found m/z
222.1146.
4.5.4. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-[4-(3-
chloropropyl)-1H-1,2,3-triazol-1-yl]-D-arabinitol (5d)
Yield: 132 mg (75%), oil. Eluent for column chromatography:
4.5. General procedure for the synthesis of 1,2,3-triazoles
19:31 EtOAc–hexane, ½a D28
ꢃ
+27.8 (c 0.10, CHCl3), Rf 0.23 (1:1
m 3406 (–OH str), 3020 (@CH str), 2361
EtOAc–hexane). IR (neat):
To a vigorously stirred solution of the azide (125 mg, 0.5 mmol)
and 1216 cmꢀ1 1H NMR (300 MHz, CDCl3 + CCl4): d 2.04–2.17 (m,
.
in t-BuOH (5 mL) was added acetylene (1.2 equiv). The reaction
2H), 2.85 (t, 2H, J = 7.2 Hz, allylic CH2), 3.53 (t, 2H, J = 6.3 Hz, CH2Cl)
3.83–3.98 (m, 3H), 4.14 (dd, 1H, J = 4.8, 8.3 Hz), 4.31–4.32 (m, 1H),
4.47–4.50 (m, 4H), 7.24–7.34 (m, 5H, ArH), 7.46 (s, 1H, triazolyl H).
13C NMR (75 MHz, CDCl3 + CCl4): d 22.9 (CH2), 32.2 (CH2), 44.2
(CH2), 52.4 (CH2N), 72.4 (CH2), 74.9 (CH2), 75.6 (CH), 82.8 (CH),
87.0 (CH) 123.1 (CH of triazole), 128.1 (ArC), 128.3 (ArC), 128.9
(ArC), 137.9 (ArCq), 146.5 (Cq of triazole). ESIMS: m/z 351; found
352 (M+H)+Å HREIMS: calcd for C17H23ClN3O3 (M+H)+ 352.1428;
found m/z 352.1410.
was initiated by the addition of
a
solution of CuSO4ꢁ5H2O
(0.2 equiv) and sodium ascorbate (0.4 equiv) in distilled water.
The colored suspension that formed was stirred at the room tem-
perature until the formation of the triazole was complete. After
completion of the reaction, ice-cold distilled water was added,
and the aqueous layer was extracted twice with CHCl3. The com-
bined organic extracts were dried, evaporated, and the crude prod-
uct was passed through a short column of silica gel to afford the
enantiomerically pure 1,2,3-triazole.
4.5.5. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-[4-(1-
4.5.1. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-(4-
methyl-1H-imidazoyl-5-yl)-1H-1,2,3-triazol-1-yl)-D-arabinitol
phenyl-1H-1,2,3-triazol-1-yl)-
D
-arabinitol (5a)
(5e)
Yield: 151 mg (86%), solid, mp 128–130 °C, Eluent for column
Yield: 73 mg (41%), oil. Eluent for column chromatography:
chromatography: 8:17 EtOAc–hexane, ½a D28
ꢃ
+25.7 (c 0.21, CHCl3),
7:93 MeOH–CHCl3, ½a D28
ꢃ
+28.3 (c 0.30, CHCl3), Rf 0.41 (3:17
MeOH–CHCl3). IR (neat): m 3402 (–OH str), 3018 (@CH str), 2926,
Rf 0.36 (1:1 EtOAc–hexane). IR (KBr):
m
3441 (–OH str), 3020
(@CH str), 2930, 2362, 1731, 1374 and 1218 cmꢀ1
.
1H NMR
2361, 1626, 1507, 1455, 1217 and 1083 cmꢀ1 1H NMR (300 MHz,
.
(300 MHz, CDCl3): d 2.77 (m, 1H, –OH), 3.87–4.04 (m, 3H), 4.22–
4.27 (m, 1H), 4.38 (br s, 1H), 4.53–4.70 (m, 4H), 7.28–7.36 (m,
6H, ArH), 7.40–7.45 (m, 2H, ArH), 7.80–7.82 (m, 2H, ArH), 7.90 (s,
1H, triazolyl H). 13C NMR (75 MHz, CDCl3): d 52.5 (CH2N), 72.5
(CH2), 74.9 (CH2), 75.9 (CH), 82.6 (CH), 86.9 (CH), 121.5 (CH of tri-
azole), 126.1 (ArC), 128.1 (ArC), 128.4 (ArC), 128.5 (ArC), 128.9
(ArC), 129.2 (ArC), 130.8 (ArCq), 137.7 (ArCq), 148.2 (Cq of triazole).
ESIMS: m/z 351; found 352 (M+H)+Å HREIMS: calcd for C20H21N3O3
(M)+ 351.1583; found m/z 351.1585.
CDCl3 + CCl4): d 3.77 (s, 4H), 3.91–3.99 (m, 2H), 4.21 (dd, 1H,
J = 5.2, 8.3 Hz), 4.32 (br s, 1H), 4.48–4.59 (m, 4H), 7.04 (s, 1H, imid-
azolyl H), 7.20–7.31 (m, 6H, 5 ArH and 1 imidazolyl H), 7.78 (s, 1H,
triazolyl H). 13C NMR (75 MHz, CDCl3 + CCl4): d = 33.9 (–NCH3),
52.5 (CH2N), 72.1 (CH2), 75.0 (CH2), 75.3 (CH), 82.5 (CH), 86.7
(CH), 123.1 (CH of triazole), 127.8 (imidazolyl CH), 128.0 (ArC),
128.2 (ArC), 128.8 (ArC), 137.9 (2 C, imidazolyl Cq and ArCq),
138.1 (Cq of triazole), 139.2 (imidazolyl CH). ESIMS: m/z 355; found
356 (M+H)+Å DART-HRESIMS: calcd for C14H28N5O3 (M+H)+
356.1682; found m/z 356.1716.
4.5.2. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-[4-(n-
octyl)-1H-1,2,3-triazol-1-yl]-D-arabinitol (5b)
4.5.6. 2,5-Anhydro-3-O-benzyl-1,4-dideoxy-4-methyl-1-(4-
Yield: 156 mg (78%), oil. Eluent for column chromatography:
phenyl-1H-1,2,3-triazol-1-yl)-D-ribitol (15a)
3:7 EtOAc–hexane, ½a D28
ꢃ
+15.2 (c 0.25, CHCl3), Rf 0.33 (1:1 EtOAc–
Yield: 113 mg (67%), solid, mp 166–168 °C, Eluent for column
hexane). IR (neat):
m
3433 (–OH str), 3020 (@CH str), 2928, 1731,
chromatography: 7:13 EtOAc–hexane, ½a D28
ꢃ
ꢀ58.8 (c 0.20, CHCl3),
1374 and 1218 cmꢀ1
.
1H NMR (300 MHz, CDCl3): d 0.89 (t, 3H,
Rf 0.37 (1:1 EtOAc–hexane). IR (KBr):
m
3433 (–OH str), 3020
J = 4.7 Hz, CH3), 1.27–1.35 (m, 10H), 1.63–1.68 (m, 2H, CH2), 2.70
(t, 2H, J = 10.8 Hz, allylic CH2), 3.84–4.03 (m, 3H), 4.16–4.21 (m,
1H), 4.36–4.37 (m, 1H), 4.48–4.62 (m, 4H) 7.28–7.37 (m, 5H,
ArH), 7.41 (s, 1H, triazolyl H). 13C NMR (75 MHz, CDCl3): d 14.4
(CH3), 23.0 (CH2) 25.9 (CH2), 29.5 (CH2), 29.6 (2C, CH2), 29.7
(CH2), 29.8 (CH2), 30.0 (CH2), 32.2 (CH2), 52.3 (CH2N), 72.4 (CH2),
74.8 (CH2), 75.8 (CH), 82.7 (CH), 87.0 (CH), 122.3 (CH of triazole),
(@CH str), 2361, 1522, 1424 and 1216 cmꢀ1 1H NMR (200 MHz,
.
CDCl3): d 2.53 (br s, 1H, –OH), 3.66 (dd, 1H, J = 4.8, 7.6 Hz), 3.84–
3.86 (m, 2H), 3.97 (br s, 1H), 4.21 (quint, 1H, J = 5.7 Hz), 4.58–
4.72 (m, 4H), 7.30–7.48 (m, 8H, ArH), 7.81–7.87 (m, 3H, 2 ArH
and 1 triazolyl H). 13C NMR (75 MHz, DMSO-d6): d 52.3 (CH2N),
68.9 (CH), 71.5 (CH2), 73.6 (CH2), 78.4 (CH), 81.1 (CH), 122.5 (CH
of triazole), 125.6 (ArC), 127.9 (ArC), 128.1 (ArC), 128.2 (ArC),

1520
L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
128.5 (ArC), 129.3 (ArC), 131.2 (ArCq), 138.6 (ArCq), 146.7 (Cq of tri-
azole). ESIMS: m/z 351; found 352 (M+H)+Å DART-HRESIMS: calcd
for C20H22N3O3 (M+H)+ 352.1661; found m/z 352.1624.
74.8 (CH2), 79.0 (CH), 83.7 (CH), 109.6 (CMe2), 120.3 (CH of tria-
zole), 126.0 (ArC), 128.4 (ArC), 128.5 (ArC), 128.7 (ArC), 128.8
(ArC), 129.1 (ArC), 130.7 (ArCq), 137.0 (ArCq), 148.3 (Cq of triazole).
ESIMS: m/z 421; found 422 (M+H)+Å HREIMS: calcd for C24H27N3O4
(M)+ 421.2002; found m/z 421.2007.
4.5.7. 2,5-Anhydro-3-O-benzyl-1,4-dideoxy-4-methyl-1-[4-(n-
octyl)-1H-1,2,3-triazol-1-yl]-D-ribitol (15b)
Yield: 124 mg (64%), oil. Eluent for column chromatography:
4.5.11. 1,4-Anhydro-3-O-benzyl-2-deoxy-2-[4-(hydroxymethyl)-
1H-1,2,3-triazol-1-yl]-5,6-O-(1-methylethylidene)-L-mannitol
(17b)
7:13 EtOAc–hexane, ½a D28
ꢃ
ꢀ25.2 (c 0.25, CHCl3), Rf 0.38 (1:1
EtOAc–hexane). IR (neat):
2929, 1373 and 1216 cmꢀ1
m
3403 (–OH str), 3020 (@CH str),
1H NMR (200 MHz, CDCl3): d 0.89
;
Yield: 101 mg (54%), solid, mp 80–82 °C, Eluent for column
chromatography: 1:99 MeOH–CHCl3, ½a D28
ꢃ
+23.0 (c 0.20, CHCl3),
3396 (–OH str), 3032
(t, 3H, J 6.5 Hz, CH3), 1.25–1.38 (m, 10H), 1.62–1.69 (m, 2H,
CH2), 2.49 (br s, 1H, –OH), 2.69 (t, 2H, J 7.8 Hz, allylic CH2),
3.55 (dd, 1H, J = 4.9, 7.5 Hz) 3.71–3.87 (m, 3H), 4.09–4.13 (m,
1H), 4.49–4.69 (m, 4H), 7.26–7.34 (m, 6H, ArH and triazolyl H).
13C NMR (75 MHz, CDCl3 + CCl4): d 14.6 (CH3), 23.1 (CH2), 26.1
(CH2), 29.7 (2C, CH2), 29.8 (2 C, CH2), 29.9 (CH2), 30.1 (CH2),
32.3 (CH2), 51.1 (CH2N), 69.6 (CH), 73.7 (CH2), 73.9 (CH2), 78.6
(CH), 80.1 (CH), 122.5 (CH of triazole), 128.6 (ArC), 128.8 (ArC),
129.1 (ArC), 137.4 (ArCq), 148.8 (Cq of triazole). ESIMS: m/z
387; found 388 (M+H)+Å HREIMS: Calcd for C22H33N3O3 (M)+
387.2522; found m/z 387.2515.
Rf 0.66 (1:19 MeOH–CHCl3,). IR (KBr):
m
(@CH str), 1657, 1456 and 1074 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
d 1.40 (s, 3H, CH3 of CMe2), 1.46 (s, 3H, CH3 of CMe2), 3.99–4.04 (m,
3H), 4.08–4.25 (m, 3H), 4.32–4.47 (m, 3H), 4.71–4.80 (m, 2H), 5.51
(td, 1H, J 5.1, 13.2 Hz), 7.08–7.11 (m, 2H, ArH), 7.28–7.31 (m, 3H,
ArH), 7.69 (s, 1H, triazolyl H). 13C NMR (75 MHz, CDCl3): d 25.7
(CH3 of CMe2), 27.1 (CH3 of CMe2), 56.6 (CH2), 62.5 (CH), 67.3
(CH2), 69.9 (CH2), 73.4 (CH), 74.5 (CH2), 79.0 (CH), 83.6 (CH),
109.5 (CMe2), 122.5 (CH of triazole), 128.4 (ArC), 128.6 (ArC),
128.7 (ArC), 137.1 (ArCq), 148.0 (Cq of triazole). ESIMS: m/z 375;
found 376 (M+H)+Å HREIMS: calcd for C19H25N3O5 (M)+ 375.1794;
found m/z 375.1808.
4.5.8. 2,5-Anhydro-3-O-benzyl-1,4-dideoxy-4-methyl-1-[4-
(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]-D-ribitol (15c)
Yield: 136 mg (77%), solid, mp 106–108 °C. Eluent for column
4.5.12. 1,4-Anhydro-3-O-benzyl-2-deoxy-5,6-O-(1-
methylethylidene)-2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]-L-
altritol (19)
chromatography: 1:49 MeOH–CHCl3, ½a D28
ꢃ
ꢀ42.5 (c 0.10, CHCl3),
Rf 0.42 (1:19 MeOH–CHCl3). IR (KBr):
m
3382 (–OH str), 3011
(@CH str), 2362, 1602, 1422 and 1216 cmꢀ1 1H NMR (300 MHz,
.
Yield: 199 mg (94%), oil. Eluent for column chromatography:
CDCl3): d 3.60–3.62 (m, 1H), 3.73–3.84 (m, 2H), 3.92–3.93 (m,
1H) 4.15 (dd, 1H, J 2.6, 7.1 Hz), 4.52–4.61 (m, 4H), 7.16–7.28 (m,
6H, ArH), 7.70–7.73 (m, 1H, ArH), 8.08–8.20 (m, 2 H, ArH, triazolyl
H), 8.51 (br s, 1H). 13C NMR (75 MHz, CDCl3): d 51.6 (CH2N), 69.5
(CH), 73.7 (CH2), 74.0 (CH2), 78.3 (CH), 80.3 (CH), 120.6 (CH of tri-
azole), 123.2 (ArC), 124.1 (ArC), 128.5 (ArC), 128.8 (ArC), 129.1
(ArC), 137.2 (ArCq), 137.3 (ArC), 148.8 (Cq of triazole), 149.7
(ArC), 150.5(ArCq). ESIMS: m/z 351; found 353 (M+H)+Å HREIMS:
Calcd for C19H20N4O3 (M)+ 352.1535; found m/z 352.1521.
9:16 EtOAc–hexane, ½a D28
ꢃ
+76.0 (c 0.63, CHCl3), Rf 0.25 (1:1
3017 (@CH str), 2927, 1602, 1459,
.
1H NMR (300 MHz, CDCl3 + CCl4): d 1.36 (s,
EtOAc–hexane). IR (neat):
m
1375 and 1216 cmꢀ1
3H, CH3 of CMe2), 1.38 (s, 3H, CH3 of CMe2), 3.78 (dd, 1H, J = 5.6,
8.4 Hz), 3.89 (t, 1H, J = 5.0 Hz), 4.06 (t, 1H, J = 8.4 Hz), 4.23–4.33
(m, 4H), 4.65, 4.77 (2 d, 2H, J = 11.6 Hz, CH2Ph), 5.29 (br s, 1H),
7.20–7.29 (m, 6H, ArH), 7.76 (t, 1H, J = 7.5 Hz, ArH), 8.17 (d, 1H,
J = 7.6 Hz, ArH), 8.33 (s, 1H, triazolyl H), 8.56 (br s, 1H, ArH). 13C
NMR (75 MHz, CDCl3 + CCl4): d 25.4 (CH3 of CMe2), 26.7 (CH3 of
CMe2), 66.7 (CH), 66.9 (CH2), 71.7 (CH2), 72.9 (CH2), 75.2 (CH),
86.0 (CH), 86.1 (CH), 110.2 (CMe2), 120.5 (ArC), 121.3 (CH of tria-
zole), 123.0 (ArC), 128.5 (ArC), 128.6 (ArC), 128.9 (ArC), 137.0
(ArCq), 137.1 (ArCq), 149.1 (ArC), 149.7 (Cq of triazole), 150.7
(ArC). ESIMS: m/z 422; found 422 (M)+Å HREIMS: calcd for
4.5.9. 2,5-Anhydro-3-O-benzyl-1,4-dideoxy-4-methyl-1-[4-(3-
chloropropyl)-1H-1,2,3-triazol-1-yl]-D-ribitol (15d)
Yield: 143 mg (53%), oil. Eluent for column chromatography:
3:2 EtOAc–hexane, ½a D28
ꢃ
ꢀ22.6 (c 0.25, CHCl3), Rf 0.46 (1:19
3413 (–OH str), 3015 (@CH str), 2360,
.
1H NMR (300 MHz, CDCl3 + CCl4): d 2.14–
MeOH–CHCl3). IR (neat):
m
C
23H27N4O4 (M+H)+ 423.2032; found m/z 423.2033.
1672 and 1217 cmꢀ1
2.21 (m, 2H), 2.88 (t, 2H, J = 7.2 Hz, allylic CH2), 3.52–3.57 (m,
3H), 3.79–3.80 (m, 2H), 3.90–3.93 (m, 1H), 4.12 (dd, 1H, J = 3.7,
7.5 Hz), 4.49–4.51 (m, 2H), 4.58–4.67 (m, 2H, CH2Ph), 7.27–7.39
(m, 6H, ArH, triazolyl H). 13C NMR (75 MHz, CDCl3 + CCl4): d 23.0
(CH2), 32.2 (CH2), 44.3 (CH2), 51.2 (CH2N), 69.6 (CH), 73.7 (CH2),
73.9 (CH2), 78.5 (CH), 80.1 (CH) 123.1 (CH of triazole), 128.6
(ArC), 128.9 (ArC), 129.2 (ArC), 137.3 (ArCq), 146.7 (Cq of triazole).
ESIMS: m/z 351; found 352 (M+H)+Å HREIMS: calcd for
4.5.13. 3,6-Anhydro-4-O-benzyl-5-deoxy-1,2-O-(1-methyl-
ethylidene)-5-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]-L-altritol
(21)
Yield: 199 mg (94%), oil. Eluent for column chromatography:
17:33 EtOAc–hexane, ½a D28
ꢃ
+108.8 (c 0.26, CHCl3), Rf 0.30 (3:2
EtOAc–hexane). IR (neat):
m
3020 (@CH str), 2927, 2362, 1658,
1467, 1377 and 1216 cmꢀ1
.
1H NMR (300 MHz, CDCl3 + CCl4): d
C
17H23ClN3O3 (M+H)+ 352.1428; found m/z 352.1427.
1.36 (s, 3H, CH3 of CMe2), 1.43 (s, 3H, CH3 of CMe2), 3.78 (dd,
1H, J = 5.4, 8.5 Hz), 4.03–4.08 (m, 2H), 4.15–4.25 (m, 2H), 4.33–
4.40 (m, 4H), 5.44–5.46 (m, 1H), 7.10–7.12 (m, 2H, ArH), 7.20–
7.28 (m, 4H, ArH), 7.78 (dt, 1H, J = 1.3, 7.6 Hz, ArH), 8.20 (d,
1H, J = 7.9 Hz, ArH), 8.36 (s, 1H, triazolyl H), 8.57 (d, 1H,
J = 4.3 Hz, ArH). 13C NMR (75 MHz, CDCl3 + CCl4): d 25.4 (CH3 of
CMe2), 27.0 (CH3 of CMe2), 61.9 (CH), 66.7 (CH2), 70.5 (CH2),
72.9 (CH2), 76.1 (CH), 79.0 (CH), 84.3 (CH), 110.2 (CMe2), 120.6
(ArC), 122.8 (CH of triazole), 123.0 (ArC), 128.4 (ArC), 128.7
(ArC), 128.8 (ArC), 137.0 (ArCq), 137.1 (ArCq), 148.8 (ArC), 149.7
(Cq of triazole), 150.8 (ArC). ESIMS: m/z 422; found 423 (M+H)+Å
HREIMS: calcd for (M)+, C23H26N4O4 422.1954; found m/z
422.1935. HREIMS: calcd for C23H27N4O4 (M+H)+ 423.2032; found
m/z 423.2035.
4.5.10. 1,4-Anhydro-3-O-benzyl-2-deoxy-5,6-O-(1-methyl
ethylidene)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)- -mannitol (17a)
L
Yield: 174 mg (85%), solid, mp 106–108 °C. Eluent for column
chromatography: 23:77 EtOAc–hexane, ½a D28
ꢃ
+68.4 (c 0.26, CHCl3),
m 3141 (@CH str), 2925,
Rf 0.26 (3:7 EtOAc–hexane). IR (KBr):
1658 and 1461 cmꢀ1 1H NMR (300 MHz, CDCl3): d 1.43 (s, 3H,
.
CH3 of CMe2), 1.49 (s, 3H, CH3 of CMe2), 4.03–4.08 (m, 3H), 4.16–
4.31 (m, 3H), 4.40 (dd, 1H, J = 3.6, 5.0 Hz) 4.43–4.53 (m, 2H), 5.61
(td, 1H, J = 5.0, 13.3 Hz), 7.08–7.11 (m, 2H, ArH), 7.23–7.29 (m,
3H, ArH), 7.37–7.47 (m, 3H, ArH), 7.77–7.80 (m, 2H, ArH), 7.94 (s,
1H, triazolyl H). 13C NMR (75 MHz, CDCl3): d 25.7 (CH3 of CMe2),
27.1 (CH3 of CMe2), 62.6 (CH), 67.4 (CH2), 70.1 (CH2), 73.4 (CH),

L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521
1521
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We are thankful to SAIF, CDRI for providing spectral data and
Mr. A. K. Pandey for technical assistance. L.V.R.R. and P.V.R. thank
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