Carbohydrate Research 345 (2010) 1515–1521

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Carbohydrate Research

journal homepage: www.elsevier .com/locate /carres

Synthesis and biological evaluation of glycal-derived novel tetrahydrofuran1,2,3-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, Indiab Division of Fermentation Technology, Central Drug Research Institute (CSIR), Lucknow 226 001, Indiac 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:Received 20 January 2010Received in revised form 20 March 2010Accepted 24 March 2010Available online 30 March 2010

Dedicated to Professor Manas Chakrabartyon the occasion of his 62nd birthday

Keywords:1,2,3-TriazolesClick chemistryTHF domain

0008-6215/$ - see front matter � 2010 Elsevier Ltd. Adoi:10.1016/j.carres.2010.03.031

q CDRI Communication No. 7659.* Corresponding author. Tel.: +91 9415403775.

E-mail address: akshaw55@yahoo.com (A.K. Shaw

Thirteen new 1,2,3-triazoles (5a–e, 15a–d, 17a–b, 19, and 21) were synthesized by ‘click’ reaction ofsugar-derived azides with commercially available acetylenes. The synthesized triazoles were testedin vitro for their biological activity, and compound 5b displayed both antibacterial and antifungal activ-ities at an MIC value of 12.5 lg/mL, while compounds 15b and 19 showed antibacterial activity at an MICvalue of 25 lg/mL.

� 2010 Elsevier Ltd. All rights reserved.

1. Introduction anticonvulsant,27 antiinflammatory, local anesthetic,28 antimalar-

In the field of pharmaceutical sciences, ‘click’ chemistry servesas a guiding principle in the quest for leads in drug discovery. Itis a modular approach that uses only the most practical and reli-able chemical transformations in modern-day chemistry.1,2 Ofthe various ‘click’ reactions that are available to us, the Cu(I)-cata-lyzed Huisgen 1,3-dipolar cycloaddition of azides and acetylenes togive 1,2,3-triazoles3–7 has gained a significant amount of attentionby 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 totagging of biological systems, such as proteins, nucleotides, andwhole organisms using bioconjugation reactions.14–17

Amongst various classes of nitrogen heterocycles, 1,2,3-triazolesand their derivatives deserve special recognition due to their wideusage in industrial applications as dyes, photographic materials, cor-rosion inhibitors, and agrochemicals such as herbicides, fungicides,and antibacterial agents.18,19 Several members of the 1,2,3-triazolefamily indeed are found to exhibit a broad spectrum of biologicalactivities such as antimicrobial,20,21 anti-HIV,22–24 antiallergic,25,26

ll rights reserved.

).

ial,29 antiviral,30 and antimycobacterial agents.31,32 Additionallysome 1,2,3-triazoles are even used as b3-selective adrenergic recep-tor antagonists,33 potassium channel activators,34 and DNA cleavingagents.35

The importance of the triazole core lies in the fact that they can-not be cleaved hydrolytically and are almost impossible to oxidizeor reduce. Though 1,2,3-triazole units are not present in naturalproducts, they are remarkably stable to metabolic transformationsand are seen in many drugs such as tazobactam and cefatrizine.36

1,2,3-Triazoles may act as H-bond donors or acceptors, dependingon their substitution. In 1,4-disubstituted 1,2,3-triazoles, N-2 andN-3 act as H-bond acceptors. The strong dipole moment of triazolepolarizes H–C-5 to a degree that it may function as a weak H-bonddonor.37 Recent studies on 1,2,3-triazoles revealed that the hydro-gen bonding and dipole interactions of the triazole core can favortheir 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, wedesigned the synthesis of a small library of stereo-diversified enan-tiopure tetrahydrofuran 1,2,3-triazole molecules of prototypes Iand II (Fig. 1) as the tetrahydrofuran backbone is found in severalmolecules of biological importance.40–46 In both the series wedecided to retain the benzyl protection group in the final moleculesas it is lipophilic in nature and is reported to influence the biolog-ical activity profile in a positive manner.47,48

O

HO OBn

Prototype I Prototype II

O

OBn

OO

N

N

N

R

N NN

R

Figure 1. Prototype molecules.

1516 L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521

2. Results and discussion

The synthesis of 1,4-disubstituted-1,2,3-triazoles of prototype Iwas undertaken with a view that the methylenic spacer betweenthe two heterocyclic rings can bring a free rotation in the molecule,and the free hydroxyl group will act as a neutral hydrogen-bonddonor that can facilitate proper binding to biomolecular target(s).To begin with, the precursor THF domain 2, easily prepared inthree 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 ofthe resulting aldehyde by NaBH4 to afford diol 3 (Scheme 1). Thediol thus obtained was transformed to azide 4 via the deoxyiodointermediate. The IR spectrum of 4 showed absorption at2106 cm�1, which is characteristic of the azido functionality, whileits FABMS displayed peak at m/z 207 corresponding to [M�N3]+�.The 13C NMR spectrum displayed peak at 53.2 ppm correspondingto a methylene carbon attached to an azido function, confirmingthe formation of the azidodeoxy compound.

Treatment of azide 4 with phenylacetylene at ambient temper-ature in the presence of CuSO4�5H2O, 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 showedpeaks 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]+� peakat m/z 352, while its HRESIMS showed an [M]+ peak, thus confirm-ing its structure. Similarly, treatment of the above-mentionedazide 4 with different alkynes viz. 1-decyne, 2-ethynylpyridine,5-chloropent-1-yne, and 5-ethynyl-1-methyl-1H-imidazole led tothe formation of their respective triazoles 5b–e in 40–78% yields

2

4

O

OBnHO

N3

i, ii

iii, iv

O

HO OBn

OO

OBnO OBn

BnOthreesteps

1

O

OBnHO

N NN

R

v

O

OBnHO

OH

3

5a R = phenyl (86%)5b R = n-octyl (78%)5c R = 2-pyridyl (64%)5d R = 3-chloropropyl (75%)5e R = 1-methyl-1H-

imidazol-5-yl (41%)

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,3 h (42% yield for two steps); (v) R H, CuSO4�5H2O (0.2 equiv), sodiumascorbate (0.4 equiv), t-BuOH–H2O (1:1), rt, 4–8 h.

in 4–8 h (Scheme 1). Their structures were established by their1H NMR, 13C NMR, and IR spectroscopic and high-resolution massspectrometric analyses.

To observe the role of stereoselectivity on biological activityprofile 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 asingle product at Rf 0.41 (3:7 EtOAc–hexane). It was then subjectedto azide displacement with NaN3 in DMF at 50–60 �C for 12 h. Butthe TLC analysis of the reaction mixture did not show any changein Rf value (0.41) or color even after 12 h of reaction time. After theusual 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 methylenecarbon attached to the iodide around the range of 10 ppm or less.Careful examination of the spectroscopic data and consideration ofa few literature precedents50–52 identified it as dioxabicyclo com-pound 10 formed by the cyclization of the hydroxyl deoxyiodointermediate under basic reaction conditions (Scheme 2). It isworth mentioning here that although the hydroxymethyl at C-2and the hydroxyl functionality at C-4 are also placed syn to eachother 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 ofour knowledge this is the first report of this kind of cyclization un-der mild reaction conditions, while the previous instances requiredthe use of strong external sources like potassium tert-butoxide,50

NaH,51 or palladium(II) catalyst.52

Next, we turned our attention to the synthesis of the triazolederivatives with opposite stereochemical configurations at C-2and C-3 of the THF ring to that of triazoles 5a–5e. In this endeavorthe 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 oxidativecleavage and reduction by H5IO6 and NaBH4, respectively. The diol13 in a standard iodination reaction followed by treatment withexcess of sodium azide, furnished the diastereomerically pureazide 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 reactionconditions furnished their corresponding 1,2,3-triazoles 15a–d ingood yields (Scheme 3).

8

O

OBnHO

Iiii

O

OBnHO

N3

iv

9

1

O

O

BnO

O

HO OBn

OO

O

OBnHO

OH

76

10

i, iithreesteps

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).

iii, iv

O

OBnHO

N3

OBnO

OBn

BnO

11

O OO

OBnHO

i, iiO

OBnHO

OH

12 13

14

O

OBnHO

N NN

R15a R = phenyl (67%)15b R = n-octyl (64%)15c R = 2-pyridyl (77%)15d R =3 -chloropropyl (53%)

v

threesteps

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) R H, CuSO4�5H2O (0.2 equiv), sodium ascorbate(0.4 equiv), 1:1 t-BuOH–H2O, rt, 5–6 h.

O OO

OBnN

NN

O OO

OBnN318

2-Ethynylpyridine (1.2 equiv),

CuSO4.5H2O (0.2 equiv),

sodium ascorbate (0.4 equiv),

1:1 t-BuOH−H2O, rt, 5−6h

19 (94%)

N

20

21 (94%)

O

OBn

OO

N

NN

N

O

N3 OBn

OO

2-Ethynylpyridine (1.2 equiv),

CuSO4.5H2O (0.2 equiv),

sodium ascorbate (0.4 equiv),

1:1 t-BuOH−H2O, rt, 5−6h

Scheme 5. Synthesis of triazoles 19 and 21.

L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521 1517

Finally, we were also interested in studying the biological activ-ity of prototype II triazole derivatives, in which the triazole ring isplaced 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 theirrespective azides 16,53 18,54 and 2054 (Scheme 4 and Scheme 5).All these synthesized triazoles were found to be >99% pure asshown by their NMR spectra and HRESIMS.

The synthesized triazole derivatives of both prototypes I and IIwere tested in vitro for their antifungal activity against Candidaalbicans, Cryptococcus neoformans, Sporothrix schenckii, Trichophy-ton mentagrophytes, Aspergillus fumigatus, Candida parapsilosis andfor antibacterial activity against Escherichia coli, Pseudomonas aeru-ginosa, Staphylococcus aureus, Klebsiella pneumoniae, Mycobacteriumtuberculosis H37Rv.

Out of all the tested compounds, only three compounds showedactivity at 50 lg/mL (Minimal Inhibitory Concentration, MIC). Theoctyl triazole 5b (prototype I) was able to inhibit the growth of S.aureus at a concentration of 12.5 lg/mL, which is comparable tothe antibacterial drug gentamycin (MIC value of 6.25 lg/mL). Thesame compound also showed growth inhibition of S. schenckiiand K. pneumoniae at concentrations of 12.5 and 25 lg/mL, respec-tively. Among the other triazole derivatives, octyl triazole 15b,whose stereochemistries at C-2 and C-3 of the tetrahydrofurancore unit were opposite to those of 5b, and pyridyl triazole 19exhibited very mild in vitro antibacterial activity at an MIC of25 lg/mL against K. pneumoniae and S. aureus, respectively. Lackof 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 OO

OBnN

NN

R

O OO

OBnN316

(1.2 equiv),CuSO4

.5H2O (0.2 equiv),

sodium ascorbate (0.4 equiv),1:1 t-BuOH−H2O, rt, 5−6h

R H

17a R = Ph (85%)17b R = CH2OH (54%)

Scheme 4. Synthesis of triazoles 17a and 17b.

phobicity of the side chain, an observation in agreement with theprevious literature reports.31,32,55

3. Conclusions

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-mentionedresults conclude that the relative stereochemistries of the substit-uents of synthesized 1,2,3-triazoles had a very little effect on theiractivity profile. However, appropriate modification/optimization ofthe above-synthesized triazoles may generate more promisingmolecules having pronounced biological activities, which is cur-rently in progress in our laboratory.

4. Experimental

4.1. Biological evaluation procedures

4.1.1. Radiometric method for drug susceptibility testing usingBACTEC 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 12Bbroth containing the test compounds. An additional control wasinoculated with 1:100 dilution of the inoculum to represent 1%of the bacterial population (102+–103+ CFU/mL). The vials wereincubated at 37 �C, and GI (Growth Index) readings were recordeddaily until the GI 1:100 control had reached 30. The concentrationof the drug producing a final GI reading lower than those in the1:100 control was considered to have inhibited more than 90% ofthe bacteria and was defined as the MIC (Minimal InhibitoryConcentration).

4.1.2. In vitro antifungal and antibacterial activity evaluationAll 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 (ATCC27736). In this process, the minimum inhibitory concentration ofcompounds was tested according to the standard microbroth

1518 L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521

dilution technique as per NCCLS guidelines.56 Briefly, testing wasperformed in flat-bottomed 96-well tissue culture plates (CELL-STAR� 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 inMuller Hinton broth (Titan Biotech Ltd, India) for bacterial strains.The concentration range of test compounds was 50–0.36 and 32–0.0018 lg/mL for standard compounds. Initial inocula of fungaland bacterial strains were maintained at 1–5 � 103 cells/mL. Theseplates 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 andC. 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 ofgrowth with respect to the growth control as observed using SOFT-max Pro 4.3 Software (Molecular Devices, Sunnyvale, USA).

4.2. General methods and materials

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 � 5 cm plates coatedwith a 0.25 mm thickness of silica gel (60F-254), and visualizationwas accomplished with CeSO4 (1% in 2.0 N H2SO4), or in some cases30% (v/v) H2SO4 in MeOH and subsequent charring over the hotplate. 1H NMR spectra were recorded at 300 MHz with TMS asthe internal reference. 13C NMR spectra were recorded at 75 MHzwith CDCl3 as the internal reference. Chemical shifts are given inparts per million downfield from the internal standard Me4Si.Yields refer to pure compounds after chromatography unlessotherwise mentioned. IR spectra were recorded on Perkin–Elmer881 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 onan Autopol III polarimeter using a 1-dm cell at 28 �C in CHCl3–MeOH as the solvent; concentrations mentioned are in g/100 mL.

4.3. General procedure for the preparation of diol

A solution of the THF domain (588 mg, 2.0 mmol) and periodicacid (592 mg, 1.3 equiv) in 10 mL of dry EtOAc was allowed to stirat room temperature for 3 h. After the completion of the reaction(TLC), the reaction was quenched with satd aq NaHCO3, and themixture was extracted with EtOAc (3 � 15 mL). The combined or-ganic layer was dried over anhyd Na2SO4 and evaporated under re-duced pressure to afford the aldehyde that was immediatelyutilized for the next reaction step.

To a precooled solution of the crude aldehyde (445 mg) inEtOH was added NaBH4 (38 mg, 0.5 equiv), and the mixturewas left stirring for 2.5 h. After the completion of reaction, excessof NaBH4 was quenched with acetone, and the whole organiclayer was evaporated and column-chromatographed to furnishthe pure diol.

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�28

D +18.4 (c 0.25, CHCl3), Rf 0.16 (1:1EtOAc–hexane). IR (neat): m 3364 (–OH str), 2922 (@CH str),2361, 1650, 1454, 1050 cm�1. 1H NMR (300 MHz, CDCl3): d 3.61(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). 13CNMR (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]+�, 154,

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�28

D �50.7 (c 0.10, CHCl3), Rf 0.12 (2:3EtOAc–hexane). IR (neat): m 3420 (–OH str), 3020 (@CH str),2925, 2361, 1633, 1521, 1455, 1216 cm�1. 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-

raphy: 7:13 EtOAc–hexane, ½a�28D �45.8 (c 0.33, CHCl3), Rf 0.86 (1:1

EtOAc–hexane). IR (neat): m 3419 (–OH str), 3019 (@C–H str), 1599,1216 cm�1. 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 (M�OH)+, 154, 136, 91. DART-HRESIMS): calcd forC12H17O4 (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 reactionmixture was decolorized by shaking it with aq Na2S2O3, and theaqueous layer was extracted thrice with EtOAc. The combined or-ganic layer was dried over anhyd Na2SO4, and evaporated todryness.

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 untilthe completion of reaction. The reaction mixture was then dilutedwith an excess of water and extracted with EtOAc (4 � 15 mL). Thecombined organic layer obtained was evaporated under high vac-uum and subjected to column chromatography to yield the pureazide.

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�28

D +47.9 (c 0.19, CHCl3), Rf 0.54 (3:7EtOAc–hexane). IR (neat): m 3447 (–OH str), 3019 (@C–H str),2106 (–N3 str), 1216 cm�1. 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; found207 (M�N3)+, 147, 136, 91. DART-HRESIMS: calcd for C12H16N1O3

(M+1�N2) 222.1130; found m/z 222.1141.

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�28D +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)+� HRESIMS: calcd for C12H15O3 (M+H)+

207.10212; found m/z 207.10173.

4.4.3. 2,5-Anhydro-1-azido-3-O-benzyl-1,4-dideoxy-4-methyl-D-ribitol (14)

Yield: 166 mg (44% from 13), oil. Eluent for column chromatog-raphy: 3:22 EtOAc–hexane, ½a�28

D �69.6 (c 0.12, CHCl3), Rf 0.43 (2:3EtOAc–hexane). IR (neat): m 3376 (–OH str), 3021 (@C–H str), 2361,2105 (–N3 str), 1216 cm�1. 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 (M�N3)+� DART-HRESIMS: calcd for C12H16NO3 (M+H�N2) 222.1130; found m/z222.1146.

4.5. General procedure for the synthesis of 1,2,3-triazoles

To a vigorously stirred solution of the azide (125 mg, 0.5 mmol)in t-BuOH (5 mL) was added acetylene (1.2 equiv). The reactionwas initiated by the addition of a solution of CuSO4�5H2O(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. Aftercompletion 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 theenantiomerically pure 1,2,3-triazole.

4.5.1. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-(4-phenyl-1H-1,2,3-triazol-1-yl)-D-arabinitol (5a)

Yield: 151 mg (86%), solid, mp 128–130 �C, Eluent for columnchromatography: 8:17 EtOAc–hexane, ½a�28

D +25.7 (c 0.21, CHCl3),Rf 0.36 (1:1 EtOAc–hexane). IR (KBr): m 3441 (–OH str), 3020(@CH str), 2930, 2362, 1731, 1374 and 1218 cm�1. 1H NMR(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)+� HREIMS: calcd for C20H21N3O3

(M)+ 351.1583; found m/z 351.1585.

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)

Yield: 156 mg (78%), oil. Eluent for column chromatography:3:7 EtOAc–hexane, ½a�28

D +15.2 (c 0.25, CHCl3), Rf 0.33 (1:1 EtOAc–hexane). IR (neat): m 3433 (–OH str), 3020 (@CH str), 2928, 1731,1374 and 1218 cm�1. 1H NMR (300 MHz, CDCl3): d 0.89 (t, 3H,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),

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)+� DART-HRESIMS: calcdfor 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 columnchromatography: 3:97 MeOH–CHCl3, ½a�28

D +42.5 (c 0.10, CHCl3),Rf 0.80 (1:19 MeOH–CHCl3). IR (KBr): m 3413 (–OH str), 3021(@CH str), 2360, 1601, 1425 and 1216 cm�1. 1H NMR (300 MHz,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, triazolylH), 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)+� HRE-IMS: calcd for C19H21N4O3 (M+H)+ 353.1614; found m/z 353.1612.

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:19:31 EtOAc–hexane, ½a�28

D +27.8 (c 0.10, CHCl3), Rf 0.23 (1:1EtOAc–hexane). IR (neat): m 3406 (–OH str), 3020 (@CH str), 2361and 1216 cm�1. 1H NMR (300 MHz, CDCl3 + CCl4): d 2.04–2.17 (m,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; found352 (M+H)+� HREIMS: calcd for C17H23ClN3O3 (M+H)+ 352.1428;found m/z 352.1410.

4.5.5. 1,4-Anhydro-3-O-benzyl-2,5-dideoxy-2-methyl-5-[4-(1-methyl-1H-imidazoyl-5-yl)-1H-1,2,3-triazol-1-yl)-D-arabinitol(5e)

Yield: 73 mg (41%), oil. Eluent for column chromatography:7:93 MeOH–CHCl3, ½a�28

D +28.3 (c 0.30, CHCl3), Rf 0.41 (3:17MeOH–CHCl3). IR (neat): m 3402 (–OH str), 3018 (@CH str), 2926,2361, 1626, 1507, 1455, 1217 and 1083 cm�1. 1H NMR (300 MHz,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; found356 (M+H)+� DART-HRESIMS: calcd for C14H28N5O3 (M+H)+

356.1682; found m/z 356.1716.

4.5.6. 2,5-Anhydro-3-O-benzyl-1,4-dideoxy-4-methyl-1-(4-phenyl-1H-1,2,3-triazol-1-yl)-D-ribitol (15a)

Yield: 113 mg (67%), solid, mp 166–168 �C, Eluent for columnchromatography: 7:13 EtOAc–hexane, ½a�28

D �58.8 (c 0.20, CHCl3),Rf 0.37 (1:1 EtOAc–hexane). IR (KBr): m 3433 (–OH str), 3020(@CH str), 2361, 1522, 1424 and 1216 cm�1. 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 ArHand 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 (CHof 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)+� DART-HRESIMS: calcdfor C20H22N3O3 (M+H)+ 352.1661; found m/z 352.1624.

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:7:13 EtOAc–hexane, ½a�28

D �25.2 (c 0.25, CHCl3), Rf 0.38 (1:1EtOAc–hexane). IR (neat): m 3403 (–OH str), 3020 (@CH str),2929, 1373 and 1216 cm�1; 1H NMR (200 MHz, CDCl3): d 0.89(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/z387; found 388 (M+H)+� HREIMS: Calcd for C22H33N3O3 (M)+

387.2522; found m/z 387.2515.

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 columnchromatography: 1:49 MeOH–CHCl3, ½a�28

D �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 cm�1. 1H NMR (300 MHz,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, triazolylH), 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)+� HREIMS:Calcd for C19H20N4O3 (M)+ 352.1535; found m/z 352.1521.

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�28

D �22.6 (c 0.25, CHCl3), Rf 0.46 (1:19MeOH–CHCl3). IR (neat): m 3413 (–OH str), 3015 (@CH str), 2360,1672 and 1217 cm�1. 1H NMR (300 MHz, CDCl3 + CCl4): d 2.14–2.21 (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)+� HREIMS: calcd forC17H23ClN3O3 (M+H)+ 352.1428; found m/z 352.1427.

4.5.10. 1,4-Anhydro-3-O-benzyl-2-deoxy-5,6-O-(1-methylethylidene)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-L-mannitol (17a)

Yield: 174 mg (85%), solid, mp 106–108 �C. Eluent for columnchromatography: 23:77 EtOAc–hexane, ½a�28

D +68.4 (c 0.26, CHCl3),Rf 0.26 (3:7 EtOAc–hexane). IR (KBr): m 3141 (@CH str), 2925,1658 and 1461 cm�1. 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),

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)+� HREIMS: calcd for C24H27N3O4

(M)+ 421.2002; found m/z 421.2007.

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)

Yield: 101 mg (54%), solid, mp 80–82 �C, Eluent for columnchromatography: 1:99 MeOH–CHCl3, ½a�28

D +23.0 (c 0.20, CHCl3),Rf 0.66 (1:19 MeOH–CHCl3,). IR (KBr): m 3396 (–OH str), 3032(@CH str), 1657, 1456 and 1074 cm�1; 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)+� HREIMS: calcd for C19H25N3O5 (M)+ 375.1794;found m/z 375.1808.

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)

Yield: 199 mg (94%), oil. Eluent for column chromatography:9:16 EtOAc–hexane, ½a�28

D +76.0 (c 0.63, CHCl3), Rf 0.25 (1:1EtOAc–hexane). IR (neat): m 3017 (@CH str), 2927, 1602, 1459,1375 and 1216 cm�1. 1H NMR (300 MHz, CDCl3 + CCl4): d 1.36 (s,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). 13CNMR (75 MHz, CDCl3 + CCl4): d 25.4 (CH3 of CMe2), 26.7 (CH3 ofCMe2), 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)+� HREIMS: calcd forC23H27N4O4 (M+H)+ 423.2032; found m/z 423.2033.

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�28

D +108.8 (c 0.26, CHCl3), Rf 0.30 (3:2EtOAc–hexane). IR (neat): m 3020 (@CH str), 2927, 2362, 1658,1467, 1377 and 1216 cm�1. 1H NMR (300 MHz, CDCl3 + CCl4): d1.36 (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 ofCMe2), 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)+�

HREIMS: calcd for (M)+, C23H26N4O4 422.1954; found m/z422.1935. HREIMS: calcd for C23H27N4O4 (M+H)+ 423.2032; foundm/z 423.2035.

L. Vijaya Raghava Reddy et al. / Carbohydrate Research 345 (2010) 1515–1521 1521

Acknowledgments

We are thankful to SAIF, CDRI for providing spectral data andMr. A. K. Pandey for technical assistance. L.V.R.R. and P.V.R. thankCSIR, N.N.M. and G.Y. thank ICMR, New Delhi, India, for the finan-cial assistance.

Supplementary data

Supplementary data (NMR spectra of all compounds) associatedwith this article can be found, in the online version, at doi:10.1016/j.carres.2010.03.031.

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