Novel lipase-catalysed highly selective acetylation studies on D-arabino- and D-threo-polyhydroxyalkyltriazoles

Article abstract of DOI:10.1016/S0968-0896(01)00350-9

Capabilities of lipases from Candida antarctica, Candida rugosa and porcine pancreas have been evaluated for regioselective acetylation of 2-phenyl-4-(D-arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-O-1',2'-isopropylidene-3',4'-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-threo-trilhydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of triazolylacylonucleosides. C. antarctica lipase and porcine pancreatic lipase exhibited exclusive selectivity for the acetylation of primary hydroxyl group over secondary hydroxyl group(s) in all three cases. Copyright

Full text of DOI:10.1016/S0968-0896(01)00350-9

Bioorganic & Medicinal Chemistry 10 (2002) 947–951
Novel Lipase-Catalysed Highly Selective Acetylation Studies on
D-Arabino- and D-Threo-polyhydroxyalkyltriazolesy
Ashok K. Prasad,a Himanshu,a Anupam Bhattacharya,a
Carl E. Olsenb and Virinder S. Parmara,*
aDepartment of Chemistry, University of Delhi, Delhi-110 007, India
bChemistry Department, Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, Frederiksberg C,
DK-1871 Copenhagen, Denmark
Received 11 June 2001; accepted 2 October 2001
Abstract—Capabilities of lipases from Candida antarctica, Candida rugosa and porcine pancreas have been evaluated for regiose-
lective acetylation of 2-phenyl-4-(d-arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(d-arabino-O-10,20-isopropylidene-
30,40-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(d-threo-trihydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of
triazolylacyclonucleosides. C. antarctica lipase and porcine pancreatic lipase exhibited exclusive selectivity for the acetylation of
primary hydroxyl group over secondary hydroxyl group(s) in all the three cases. # 2002 Elsevier Science Ltd. All rights reserved.
Introduction
Recently, enzymes have emerged as economical and
environment-friendly catalysts to carry out highly regio-,
chemo- and stereoselective reactions. We have also
demonstrated the capabilities of lipases from Candida
antarctica and Pseudomonas sp for regioselective acyla-
tion of hydroxyl groups in 2-deoxy-d-ribose and d-
ribose,13 and for the acylation of one out of the two
similar hydroxymethyl groups present in some 4-C-
hydroxymethyl-1,2-O-isopropylidene-a-d-pentofuranose
derivatives,14,15 key intermediates for the synthesis of
bicyclonucleosides.16,17 We herein wish to report lipase-
catalysed highly selective acetylation of hydroxyl groups
present in 2-phenyl-4-(d-arabino-10,20,30,40-tetrahydroxy-
butyl)-2H-1,2,3-triazole (1), 2-phenyl-4-(d-arabino-O-
10,20-isopropylidene-30,40-dihydroxybutyl)-2H-1,2,3-tria-
zole (3) and 2-phenyl-4-(d-threo-10,20,30-trihydroxy-
propyl)-2H-1,2,3-triazole (5) using vinyl acetate as
acetylating agent in organic solvents.
The control of regiochemistry and stereochemistry dur-
ing the course of chemical transformations is a great
challenge for the synthetic organic chemist. For exam-
ple, selective manipulation of hydroxyl groups in poly-
hydroxy compounds is always required when sugars,
polyols or polyphenolics are used as starting mate-
rials.1ꢀ5 Among the different polyhydroxy com-
pounds, carbohydrates have always been a focal
point because of their chiral pool characteristics.6 In
the recent past, a plethora of work has been done
in the area of modification of sugars towards the
synthesis of sugar modified nucleosides and nucleo-
tides in search of antiviral candidates, for example
AZT, ddc, d4T, and so on and in antisense and
antigene strategies for selective regulation of gene
expression.7ꢀ10 Synthesis of these highly functionalised
bioactive molecules containing modified sugar moieties
requires multi-step protocols involving protections and
deprotections of hydroxyl groups which result in overall
low yields.11,12
Results and Discussion
Synthesis
The triazolyl sugar 1 was prepared in two steps starting
from glucose via its conversion into phenylosazone,
followed by oxidative cyclisation of the osazone with
1% CuSO4 in an overall yield of 43% (Scheme 1).18 The
conversion of tetrahydroxybutyltriazole 1 to its di-iso-
yA part of this work was presented at the IUPAC International Sym-
posium on Green Chemistry held in New Delhi (India) on 10–13 Jan-
uary 2001.
*Corresponding author. Tel.:+91-11-766-6555; fax:+91-11-766-7206;
e-mail: virparmar@yahoo.co.in
0968-0896/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved.
PII: S0968-0896(01)00350-9

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A. K. Prasad et al. / Bioorg. Med. Chem. 10 (2002) 947–951
propylidene derivative 2 by acetone–anhydrous ferric
chloride method,19 followed by the selective deprotection
of 30,40-O- isopropylidene function led to the formation
of 10,20-O-isopropylidene-30,40-dihydroxybutyltriazole 3
in 68% yield (Scheme 1). The NaIO4 oxidation, followed
by NaBH4 reduction20 of mono-isopropylidine deriva-
tive 3 lead to the formation of 2-phenyl-4-(d-threo-O-
10,20-isopropylidene-30-hydroxypropyl)-2H-1,2,3-triazole
4, which on deprotection of isopropylidene protection
afforded threo-trihydroxypropyltriazole 5 in 60% yield
(Scheme 1). The structures of all the five compounds 1–
5, prepared in our laboratory under a programme of
synthesis of triazolylacyclonucleosides for antiviral
activity evaluation, were unambiguously established on
the basis of their spectral analysis. The melting points of
two known compounds, that is, triazolyl sugars 1 and 5
were found identical with those reported in the litera-
ture,18,21 however the complete spectral data for triazolyl
sugars 1 and 5 is being reported here for the first time.
THF (20 mL) was incubated with CAL/PPL (150 mg) in
an incubator shaker at 42–45 ꢁC and the progress of the
reaction was monitored by HPLC and/or TLC. On
completion of the reaction, enzyme was filtered off and
solvent removed under reduced pressure to obtain the
crude product, which on purification by column chro-
matography afforded the acetylated product and the
unreacted starting compound. It was observed that both
CAL and PPL exclusively acetylate the primary
hydroxyl group over the secondary hydroxyl group(s) in
all the three triazolyl sugars 1, 3 and 5 leading to the for-
mation of 2-phenyl-4-(d-arabino-40-acetoxy-10,20,30-trihy-
droxy-butyl)-2H-1,2,3-triazole (6), 2-phenyl-4-(d-arabino-40-
acetoxy-O-10,20-isopropylidene-30-hydroxybutyl)-2H-1,2,3-
triazole (7) and 2-phenyl-4-(d-threo-30 -acetoxy-10,20 -
dihydroxypropyl)-2H-1,2,3-triazole (8), respectively. All
the three partially acetylated compounds 6–8 are new
in literature and have been fully characterised on the
basis of their spectral data. As indicated during
screening, the rate of acetylation of primary hydroxyl
groups of triazolyl sugars 1, 3 and 5 catalysed by
CAL in DIPE was much faster as compared to the
rate of acetylation catalysed by PPL in THF. Thus,
acetylation of triazolyl sugar 1 to monoacetate 6
catalysed by CAL in DIPE was completed in 2 h,
whereas the conversion was only 72% even after 26 h of
incubation of 1 with PPL in THF. Similar trends
were observed for the other two triazolyl sugars 3
and 5 (Table 1). The acetylation reaction catalysed by
PPL practically stops after 68–76% conversion of the
starting compounds 1, 3 and 5 into the monoacetylated
products 6, 7 and 8; both the lipases exclusively acety-
late the primary hydroxyl group in these compounds. It
is interesting to note that the rate of acetylation of the
primary hydroxyl group catalysed by CAL in DIPE
increases as the number of hydroxyl group in the sub-
strate increases. Thus, the rate of acetylation of tetra-
hydroxybutyltriazole 1 catalysed by CAL in DIPE was
4 and 1.75 times faster than the rate of acetylation of
Regioselective enzymatic acetylation
Different lipases, that is C. antarctica lipase (CAL) and
Candida rugosa lipase (CRL) in diisopropyl ether
(DIPE), and porcine pancreatic lipase (PPL) in tetra-
hydrofuran (THF) were screened for the selective acet-
ylation of hydroxyl groups in tetra-, di- and
trihydroxylated triazolyl sugars 1, 3 and 5. The selection
of solvent for different lipases was done on the basis of
our earlier experience.4 No appreciable conversion was
observed in the case of acetylation of compounds 1, 3 or
5 catalysed by CRL in DIPE even after 34 h of incuba-
tion at 42–45 ꢁC. Further, the rate of acetylation of
triazolyl sugars 1, 3 and 5 catalysed by PPL in THF was
very slow with respect to the acetylation catalysed by
CAL in DIPE (Table 1).
In a typical reaction, a solution of the triazolyl sugar (1,
3 or 5, 1 mmol) and vinyl acetate (4.4 mmol) in DIPE/
Scheme 1. Reagents and conditions: (i) PhNHNH2, acetic acid, H2O, reflux; (iii) 1% aq CuSO4.5H2O solution, H2O, reflux; (iii) FeCl3, acetone,
stirring, 25–28 ꢁC; (iv) 80% acetic acid, stirring, 25–28 ꢁC; (v) NaIO4, H2O/dioxane (1:1), stirring, 25–28 ꢁC; (vi) NaBH4, H2O/dioxane (1:1) ethanol,
stirring, 25–28 ꢁC; (vii) 80% acetic acid, reflux; (viii) CAL-DIPE/PPL-THF, vinyl acetate, 42–45 ꢁC.

A. K. Prasad et al. / Bioorg. Med. Chem. 10 (2002) 947–951
949
Table 1. Regioselective acetylation of triazolyl sugars 1, 3 and 5 mediated by lipases at 42–45ꢁC using vinyl acetate as acylating agenta
Substrate
Lipase-solvent
(RT in h)
Product
% Yield in case of
reaction with
CAL-DIPE/PPL-THF
2-Phenyl-4-(d-arabino-
10,20,30,40-tetrahydroxy-
butyl)-2H-1,2,3-triazole (1)
2-Phenyl-4-(d-arabino-
O-10,20-isopropylidene-
30,40-dihydroxybutyl)-
2H-1,2,3-triazole (3)
2-Phenyl-4-(d-threo-10,
20,30-trihydroxypropyl)-
2H-1,2,3-triazole (5)
CAL-DIPE/
PPL-THF
(2/26)
CAL-DIPE/
PPL-THF
(8/72)
2-Phenyl-4-(d-arabino-40-
acetoxy-10,20,30-trihydroxy-
butyl)-2H-1,2,3-triazole (6)
2-Phenyl-4-(d-arabino-
98/72
95/76
40-acetoxy-O-10,20-iso-
propylidene-30-hydroxy-
butyl)-2H-1,2,3- triazole (7)
2-Phenyl-4-(D-threo-30-
acetoxy-10,20-dihydroxy-
propyl)-2H-1,2,3-triazole (8)
CAL-DIPE/
PPL-THF
(3.5/48)
97/68
aAll these reactions when performed under identical conditions but without addition of the enzyme did not yield any product.
dihydroxybutyltriazole 3 and trihydroxypropyltriazole
5, respectively (Table 1). This indicates that the interac-
tion of the secondary hydroxyl groups with the active
site of the enzyme facilitates the acetylation of the pri-
mary hydroxyl group present in the substrate. This is
the first report of enzyme-catalysed selective acetylation
studies on triazolyl sugars.
coated Merck silica gel 60F254 plates; the spots were
detected either by UV light or by charring with 4%
alcoholic H2SO4. Reactions were monitored at l254 nm
on a Shimadzu LC-10AS HPLC instrument with SPD-
10A UV–Vis detector and Shimpack CLC-ODS
(4.6ꢂ150 mm) reverse phase column; solvent system used
was methanol–water (3:2) at a flow rate of 0.50 mL/min.
2-Phenyl-4-(D-arabino-10,20,30,40-tetrahydroxybutyl)-2H-
1,2,3-triazole (1). The tetrahydroxybutyltriazole 1 was
prepared from glucose phenylosazone by the method of
Hann and Hudson,18 it was obtainedꢁ as a white crys-
talline solid in 54% yield, mp 194–195 C (lit.21 mp 195–
196 ꢁC). Rf 0.28 (chloroform–methanol, 9:1); IR
(Nujol): 3287 (OH), 2923, 2360, 1596, 1462, 1377, 1089
and 968 cmꢀ1; 1H NMR(300 MHz, DMSO- d6): d 3.51–
3.55(1H, m, C-40Ha), 3.62–3.71 (3H, m, C-20H, C-30H
and C-40Hb), 4.35 (1H, t, J=5.7 Hz, OH), 4.60 (1H, d,
J=6.8 Hz, OH), 4.67 (1H, d, J=4.7 Hz, OH), 5.15 (1H,
d, J=4.7 Hz, OH), 5.25 (1H, d, J=6.9 Hz, C-10H),
7.33–7.38 (1H, m, C-400H), 7.48–7.54 (2H, m, C-200H and
C-600H), 7.93 (1H, s, C-5H) and 7.99 (2H, m, C-300H and
C-500H); 13C NMR(75.5 MHz, DMSO- d6): d 61.75,
63.87, 69.29 and 72.18 (C-10, C-20, C-30 and C-40), 116.27
(C-300 and C-500), 125.23 (C-400), 127.55 (C-200 and C-600),
133.26 (C-5), 137.67 (C-100) and 151.06 (C-4); EIMS, m/z
(% rel. int.): 247([M-18]+, 10), 187 (15), 174 (100), 159
(5), 91 (45) and 77 (32).
Conclusion
The above study has revealed that CAL in DIPE exhi-
bits exclusive selectivity for the acetylation of primary
hydroxyl group over secondary hydroxyl group(s) in
triazolyl sugars. The turn over of the acetylation reac-
tion was very high and 95–98% conversion was
observed in 2–8 h. The enzymatic method developed for
the selective acetylation of primary hydroxyl group in
triazolyl sugars may offer a significant advantage over
the chemical methods for selective manipulation of dif-
ferent hydroxyl groups en route to multistep synthesis
of bioactive molecules of this class. All these reactions
when performed under identical conditions but without
addition of the enzyme did not yield any product.
Experimental
General
2-Phenyl-4-(D-arabino-di-O-10,20,30,40-isopropylidenebutyl)-
Melting points were determined on a Mettler FP62
instrument and are uncorrected. The IRspectra were
recorded either on a Perkin-Elmer model 2000 FT-IRor
RXI FT-IR spectrometer. The 1H NMRand 13C NMR
spectra were recorded on Bruker AC-300 spectrometer
at 300 and at 75.5 MHz, respectively using TMS as
internal standard. The chemical shift values are on d
scale and the coupling constants (J) are in Hz. The
EIMS were recorded on a Jeol AX 505 W instrument at
70 eV. The C. antarctica lipase immobilised on accurel
was gifted by Novo Nordisk Co. and used as such. The
enzymes, porcine pancreatic lipase (PPL, Type II) and
C. rugosa lipase (CRL, Type VII) were purchased from
Sigma Chemical Co. (USA) and used after storing in
vacuo over P2O5 for 24 h. The organic solvents (THF
and DIPE) used were distilled over activated molecular
sieves (4 A). Analytical TLCs were performed on pre-
2H-1,2,3-triazole (2).
A
suspension of tetra-
hydroxybutyltriazole (1, 1.3 g, 5 mmol) and anhydrous
FeCl3 (750 mg) in dry acetone (125 mL) was stirred at
25–28 ꢁC and the progress of the reaction was mon-
itored by TLC. On completion, the reaction was termi-
nated by addition of 10% solution of potassium
carbonate (10 mL); solvent removed under reduced
pressure and the brown syrup obtained was extracted
with chloroform (3ꢂ50 mL). The combined organic
layer was washed with water (2ꢂ50 mL), dried over
Na2SO4 and solvent removed under reduced pressure to
afford the crude product which was purified by silica gel
column chromatography using petroleum ether–ethyl
acetate as eluent to obtain pure di-O-isopropylidene
derivative 2 as a colourless viscous oil (1.6 g) in 90%
yield. Rf 0.30 (petroleum ether–ethyl acetate, 9:1); IR
(Nujol): 1600, 1499, 1463, 1372, 1217, 1071, 967, 844

950
A. K. Prasad et al. / Bioorg. Med. Chem. 10 (2002) 947–951
and 755 cmꢀ1
;
1H NMR(300 MHz, CDCl 3): d 1.18,
m, C-20H), 5.17 (1H, d, J=8.4 Hz, C-10H), 7.33–7.38
(1H, m, C-400H), 7.45–7.50 (2H, m, C-200H and C-600H),
7.84 (1H, s, C-5H) and 8.03–8.06 (2H, m, C-300H and C-
1.22, 1.40 and 1.42 (12H, 4s, 3H each, 4ꢂCH3), 3.94 and
4.04 (2H, 2dd, 1H each, J=4.7 Hz and 8.6 Hz, and 6.1
Hz and 8.6 Hz, respectively, C-40Ha and C-40 Hb), 4.15–
4.21 (1H, m, C-30H), 4.27 (1H, t, J=7.1 Hz, C-20H),
5.09 (1H, d, J=7.2 Hz, C-10H), 7.20–7.29 (1H, m, C-
400H), 7.33–7.39 (2H, m, C-200H and C-600H), 7.73 (1H, s,
C-5H) and 7.96–7.99 (2H, m, C-300H and C-500H); 13C
NMR(75.5 MHz, CDCl 3): d 24.19, 25.42, 25.79 and
26.05 (4ꢂCH3), 65.85 (C-40), 72.80 and 76.50 (C-20 and
C-30), 80.23 (C-10), 108.74 and 109.58 (2ꢂC(CH3)2),
117.84 (C-300 and C-500), 126.48 (C-400), 128.19 (C-200 and
C-600), 133.36 (C-5), 138.77 (C-100) and 147.21 (C-4);
EIMS, m/z (% rel. int.): 345 ([M+], 25), 330 (25), 272
(30), 229 (100), 188 (95), 158 (50), 101 (95), 91 (25), 77
(40) and 43 (95).
500H); 13C NMR(75.5 MHz, CDCl ): d 27.15 and 27.33
3
(2ꢂCH3), 61.37 (C-30), 72.17 (C-20), 81.99 (C-10), 110.63
(C(CH3)2), 119.26 (C-400), 128.02 (C-300 and C-500),
129.63 (C-200 and C-600), 134.27 (C-5), 140.04 (C-100) and
148.04 (C-4); EIMS, m/z (% rel. int.): 275([M]+, 36),
260 (75), 242 (15), 230 (10), 218 (95), 216 (5), 200 (75),
188 (75), 131 (15), 91 (65), 77 (95) and 59 (100).
2-Phenyl-4-(D-threo-10,20,30-trihydroxypropyl)-2H-1,2,3-
triazole (5). A solution of the isopropylidenetriazole 4
(550 mg, 2 mmol) in 80% acetic acid (25 mL) was
refluxed for 2 h when TLC showed complete conversion
of the starting material into a slow moving spot. The
solvent was evaporated under reduced pressure to
afford the trihydroxypropyltriazole 5 as a wꢁhite crystal-
line solid (282 mg) in 60% yield; mp 87–89 C (lit21 mp
88–90 ꢁC). Rf 0.35 (chloroform–methanol, 9:1); IR
2-Phenyl-4-(D-arabino-O-10,20-isopropylidene-30,40-dihy-
droxybutyl)-2H-1,2,3-triazole (3). A solution of 2 (1.4 g,
4 mmol) in 80% acetic acid (50 mL) was stirred at 25–
28 ꢁC for 12 h when TLC showed complete conversion
of starting material into a slow moving product.
Removal of acetic acid under reduced pressure afforded
the title compound 3 as a white solid (830 mg) in 68%
yield; mp 65–66 ꢁC. Rf 0.25 (petroleum ether–ethyl ace-
tate, 7:3); IR(Nujol): 3420 (OH), 1599, 1498, 1462,
(Nujol): 3292 (OH), 1597, 1501, 1448, 1379, 1265, 1087,
1
942, 892 and 753 cmꢀ1; H NMR(300 MHz, CD OD):
3
d 3.60 (1H, dd, J=6.3 Hz and 11.2 Hz, C-30Ha), 3.74
(1H, dd, J=5.2 Hz and 11.2 Hz, C-30 Hb), 3.92–3.97
(1H, q, J=5.1 Hz, C-20H), 4.99 (1H, d, J=4.8 Hz, C-
10H), 7.35–7.40 (1H, m, C-400H), 7.49–7.54 (2H, m, C-
200H and C-600H), 7.93 (1H, s, C-5H) and 8.04–8.07 (2H,
1375, 1242, 1216, 1070, 968, 889 and 757 cmꢀ1 1H
;
NMR(300 MHz, CDCl ): d 1.47 and 1.54 (6H, 2s, 3H
m, C-300H and C-500H); 13C NMR(75.5 MHz, CD OD):
3
3
each, 2ꢂCH3), 2.80 (2H, br s, 2ꢂOH), 3.76–3.81 (2H,
m, C-40H), 4.04–4.08 (1H, m, C-30H), 4.30–4.34 (1H, m,
C-20H), 5.25 (1H, d, J=7.7 Hz, C-10H), 7.33–7.38 (1H,
m, C-400H), 7.45–7.49 (2H, m, C-200H and C-600H), 7.85
(1H, s, C-5H) and 7.98–8.01 (2H, m, C-300H and C-
d 60.98 and 64.95 (C-20 and C-30), 72.25 (C-10), 116.36
(C-400), 125.10 (C-300 and C-500), 127.13 (C-200 and C-600),
132.46 (C-5), 137.60 (C-100) and 149.32 (C-4); EIMS, m/z
(% rel. int.): 235 ([M]+, 10), 218 (15), 189 (10), 174
(100), 149 (25), 91 (55), 83 (85) and 77 (45).
500H); 13C NMR(75.5 MHz, CDCl ): d 26.38 and 26.75
3
(2ꢂCH3), 63.12 (C-40), 71.39 and 72.17 (C-20 and C-30),
81.32 (C-10), 110.00 (C(CH3)2), 118.75(C-300 and C-500),
127.72 and 129.27 (C-200, C-400 and C-600), 133.85 (C-5),
140.00 (C-100) and 150.00 (C-4); EIMS, m/z (% rel. int.):
304 ([M-1]+, 20), 289 (30), 230 (35), 216 (75), 188 (100),
158 (55), 91 (40), 77 (60) and 43 (95).
General procedure of Candida antarctica lipase-
catalysed acetylation of triazolyl sugars 1, 3 and 5
To a solution of the triazolyl sugar (1, 3 or 5, 1 mmol) in
dry diisopropyl ether (20 mL) was added vinyl acetate
(4.4 mmol), followed by C. antarctica lipase (150 mg).
The suspension was stirred at 42–45 ꢁC in an incubator
shaker and progress of the reaction monitored periodi-
cally by HPLC and/or TLC. The reaction was quenched
on completion by filtering off the enzyme and the sol-
vent evaporated to dryness in vacuo to afford the pure
partially acetylated triazolyl sugars 6–8 in 95–98%
yields.
2-Phenyl-4-(D-threo-O-1,2-isopropylidene-30-hydroxypro-
pyl)-2H-1,2,3-triazole (4). To a solution of 3 (762 mg,
2.5 mmol) in 1:1 mixture of H2O–dioxane (25 mL),
NaIO4 (2.5 mmol, 532 mg in 8 mL water) was added
and the reaction mixture was stirred for 90 min at 25–
28 ꢁC when TLC showed complete conversion of the
starting material into a fast moving product. Ethanol
(15 mL) was added to the reaction mixture, the white
solid that precipitated out was filtered off, NaBH4 (47
mg, 1.25 mmol) was added to the clear filtrate and the
contents stirred for 30 min at 25–28 ꢁC. The reaction
mixture was filtered, solvent evaporated under reduced
pressure and the crude product thus obtained was pur-
ified by column chromatography on silica gel using pet-
roleum ether–ethyl acetate (9:1) as eluent to afford
isopropylidenepropyltriazole 4 as a colourless oil (605
mg) in 88% yield. Rf 0.45 (petroleum ether–ethyl ace-
tate, 3:2); IR(Nujol): 3447 (OH), 1599, 1462, 1375,
2-Phenyl-4-(D-arabino-40-acetoxy-10,20,30-trihydroxybutyl)-
2H-1,2,3-triazole (6). It was obtained as a white solid
(301 mg) in 98% yield; mp 112–13 ꢁC. Rf 0.40 (petro-
leum ether–ethyl acetate, 9:1); IR(Nujol): 3316 (OH),
1738 (OCOCH3), 1598, 1461, 1377, 1071, 967 and 754
cmꢀ1 1H NMR(300 MHz, CDCl 3): d 2.12 (3H, s,
;
OCOCH3), 3.07, 3.17 and 3.38 (3H, 3br s, 1H each,
3ꢂOH), 3.97–4.10 (2H, m, C-40H), 4.31–4.37 and 4.42–
4.48 (2H, 2m, 1H each, C-20H and C-30H), 5.26 (1H, br
s, C-10H), 7.32–7.37 (1H, m, C-400H), 7.45–7.49 (2H, m,
C-200H and C-600H), 7.88 (1H, s, C-5H) and 7.99–8.02 (2H,
m, C-300H and C-500H); 13C NMR(75.5 MHz, CDCl 3): d
21.28 (OCOCH3), 66.70 (C-40), 70.98 and 73.36 (C-20
and C-30), 77.83 (C-10), 119.25 (C-300 and C-500), 128.10
and 129.72 (C-200, C-400 and C-600), 134.72 (C-5), 139.97
1220, 1164, 1070, 968, 857 and 757 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d 1.54 and 1.55 (6H, 2s, 3H each,
2ꢂCH3), 2.25 (1H, br s, OH), 3.79–3.83 and 4.10–4.13
(2H, 2m, 1H each, C-30Ha and C-30 Hb), 4.27–4.30 (1H,

A. K. Prasad et al. / Bioorg. Med. Chem. 10 (2002) 947–951
951
(C-100), 150.46 (C-4) and 172.36 (CO); EIMS, m/z (%
rel. int.): 247 ([M–CH2CO–H2O]+, 8), 172 (100), 158
(15), 117 (12), 91 (88), 77 (58), 64 (31) and 43 (74).
and Industrial Research (CSIR, New Delhi) for finan-
cial assistance.
2-Phenyl-4-(D-arabino-40-acetoxy-O-10,20-isopropylidene-
30-hydroxybutyl)-2H-1,2,3-triazole (7). It was obtained
as a colourless viscous oil (330 mg) in 95% yield. Rf 0.35
(petroleum ether–ethyl acetate, 9:1); IR(Nujol): 3446
(OH), 1741 (OCOCH3), 1462, 1376, 1241, 1071, 967 and
758 cmꢀ1; 1H NMR(300 MHz, CDCl 3): d 1.51 and 1.53
(6H, 2s, 3H each, 2ꢂCH3), 2.04 (3H, s, OCOCH3), 2.85
(1H, br s, OH), 4.16–4.21 (2H, m, C-40H), 4.29–4.36
(2H, m, C-20H and C-30H), 5.28 (1H, d, J=7.6 Hz, C-
10H), 7.33–7.36 (1H, m, C-400H), 7.45–7.51 (2H, m, C-200H
a0n0 d C-600H), 070 .84 (1H, s, C-5H) and 8.02–8.05 (2H, m, C-
3 H and C-5 H); 13C NMR(75.5 MHz, CDCl 3): d 26.58
and 26.83 (2ꢂCH3), 29.61 (OCOCH3), 61.97 and 65.44
(C-30 and C-40), 70.35 (C-20), 80.57 (C-10), 110.41
(C(CH3)2), 118.81 (C-300 and C-500), 127.64 and 129.22 (C-
200, C-400 and C-600), 133.92 (C-5), 139.52 (C-100), 148.22
(C-4) and 171.11 (CO); EIMS, m/z (% rel. int.): 347
([M]+, 45), 332 (35), 290 (50), 272 (25), 230 (60), 188
(100), 158 (60), 135 (10), 103 (30), 91 (40) and 77 (60).
References and Notes
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Perkin Trans. 1, 1995, 2203.
2. Schmid, R. D.; Verger, R. Angew. Chem., Int. Ed. Eng.
1998, 37, 1608.
3. Zaks, A.; Dodds, D. R. Drug Discov. Today 1997, 2,
513.
4. Parmar, V. S.; Prasad, A. K.; Pati, H. N.; Kumar, R.;
Azim, A.; Roy, S.; Errington, W. Bioorg. Chem. 1999, 27,
119.
5. Prasad, A. K.; Pati, H. N.; Azim, A.; Trikha, S.; Poonam
Bioorg. Med. Chem. 1999, 7, 1973.
6. Collins, P.; Ferrier, R. Monosaccharides: their Chemistry
and Their Roles in Natural Products; John Wiley and Sons:
UK, 1995; p. 431.
7. Wengel, J. Acc. Chem. Res. 1999, 32, 301.
8. Meldgaard, M.; Wengel, J. Perkin Trans. 1, 2000, 3539.
9. Sekiyama, T.; Hatsuya, S.; Tanaka, Y.; Uchiyama, M.;
Ono, N.; Iwayama, S.; Oikaw, M.; Suzuki, K.; Okunishi, M.;
Tsuji, T. J. Med. Chem. 1998, 41, 1284.
2-Phenyl-4-(D-threo-30 -acetoxy-10,20 -dihydroxypropyl)-
2H-1,2,3-triazole (8). It was obtained as a white solid
(269 mg) in 97% yield; mp 131–32 ꢁC. Rf 0.50 (petro-
leum ether–ethyl acetate, 9:1); IR(Nujol): 3357 (OH),
10. Hirota, K.; Monguchi, Y.; Sajiki, H.; Sako, M.; Kitade,
Y. Perkin Trans. 1, 1998, 41.
11. Rich, J. O.; Bedll, B. A.; Dordick, J. S. Biotech. Bioengg.
1995, 45, 426.
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Tetrahedron Lett. 1995, 36, 6163.
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Tetrahedron 1998, 54, 3607.
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735.
1736 (OCOCH3), 1461, 1376, 1228, 1062, 977, 810 and
1
757 cmꢀ1; H NMR(300 MHz, CDCl ): d 2.10 (3H, s,
3
OCOCH3), 3.09 and 3.16 (2H, 2br s, 1H each, 2ꢂOH),
4.20–4.27 and 4.29–4.37 (3H, 2m, 2H and 1H each,
respectively, C-20H and C-30H), 4.95(1H, br s, C-10H),
7.33–7.38 (1H, m, C-400H), 7.45–7.50 (2H, m, C-200H and
C-600H), 7.86 (1H, s, C-5H) and 8.01–8.04 (2H, m, C-
300H and C-500H); 13C NMR(75.5 MHz, CDCl 3): d 21.23
(OCOCH3), 65.44 and 67.48 (C-20 and C-30), 72.54 (C-10),
119.26 (C-300 and C-500), 128.13 and 129.72 (C-200, C-400 and
C-600), 134.52 (C-5), 139.99 (C-100), 149.65 (C-4) and 171.74
(CO); EIMS, m/z (% rel. int.): 277 ([M]+, 10), 260 (15),
234 (7), 217 (15), 200 (10), 174 (100), 91 (45) and 77 (40).
19. Singh, P. P.; Gharia, M. M.; Dasgupta, F.; Srivastava,
H. C. Tetrahedron Lett., 1977, 439.
20. Nielsen, P.; Kirpekar, F.; Wengel, J. Nucleic Acids Res.
1994, 22, 703.
Acknowledgements
We thank the Danish International Development
Agency (DANIDA, Denmark) and Council of Scientific
21. Tipson, R. S. Methods in Carbohydrates Chemistry; Aca-
demic Press: New York, 1963; Vol. 2, p 16.