Highly efficient and selective biocatalytic acylation studies on triazolylsugars

Article abstract of DOI:10.1016/j.tet.2003.10.059

Different acid anhydrides (of C₂ to C₇ aliphatic fatty acids and benzoic acid) have been used to study the selective acylation of primary/secondary hydroxyl groups in 2-phenyl-4-(D-threo-1′,2′, 3′-trihydroxypropyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-erythro-1′, 2′,3′-trihydroxypropyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino- 1′,2′,3′,4′-tetrahydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-lyxo-1′,2′,3′,4′-tetrahydroxybutyl)-2H-1, 2,3-triazole in the presence of Candida antarctica lipase B in diisopropyl ether. Among the different acid anhydrides, butanoic anhydride was found to be the most efficient acylating agent (for butanoylation); for acetylation, vinyl acetate gave the best results. The reactions with both these acylating agents were highly selective and efficient yielding exclusively the monoacylated products in 95-99% yields in 1-5 h.

Full text of DOI:10.1016/j.tet.2003.10.059

Tetrahedron 59 (2003) 10269–10277
Highly efficient and selective biocatalytic acylation studies
on triazolylsugars
a,b
Anupam Bhattacharya, Ashok K. Prasad, Jyotirmoy Maity, Himanshu, Poonam,
a,*
a
a,b
a
c
Carl E. Olsen, Richard A. Gross and Virinder S. Parmar
b
a,b,
*
a
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
NSF Centre for Biocatalysis and Bioprocessing of Macromolecules, Department of Chemistry, Polytechnic University,
b
Six Metrotech Centre, Brooklyn, NY 11201, USA
Department of Chemistry, Royal Veterinary and Agricultural University, Frederiksberg C, DK-1871 Copenhagen, Denmark
c
Received 14 April 2003; revised 19 September 2003; accepted 16 October 2003
Abstract—Different acid anhydrides (of C
2 7
to C aliphatic fatty acids and benzoic acid) have been used to study the selective acylation of
0
0
0
0
0
0
primary/secondary hydroxyl groups in 2-phenyl-4-(D-threo-1 ,2 ,3 -trihydroxypropyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-erythro-1 ,2 ,3 -
0
0
0
0
trihydroxypropyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-1 ,2 ,3 ,4 -tetrahydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-lyxo-
0 0 0
0
1
,2 ,3 ,4 -tetrahydroxybutyl)-2H-1,2,3-triazole in the presence of Candida antarctica lipase B in diisopropyl ether. Among the different
acid anhydrides, butanoic anhydride was found to be the most efficient acylating agent (for butanoylation); for acetylation, vinyl acetate gave
the best results. The reactions with both these acylating agents were highly selective and efficient yielding exclusively the monoacylated
products in 95–99% yields in 1–5 h.
q 2003 Elsevier Ltd. All rights reserved.
1
. Introduction
these bioactive compounds involving several protection and
deprotection steps, which often result in relatively low
yields, thus making the whole protocol cumbersome and
Enzyme-catalyzed organic reactions have provided a great
impetus to organic synthesis during the last two decades.
Enzymes, especially lipases are known for their low cost
and great tolerance towards their substrates. In fact lipase-
catalyzed acylation and deacylation reactions today
represent an important class of enzymatic transformations
9
,10
expensive.
We have shown in our recent publications the capability of
Candida antarctica lipase, Pseudomonas sp. lipase and
porcine pancreatic lipase for carrying out highly selective
protection of hydroxyl groups in 2-deoxy-D-ribose, 4-C-
hydroxymethylated furanose derivatives and triazolyl-
1
–3
in organic synthesis.
1
1–15
Carbohydrates are probably the most complex of all
polyhydroxy compounds due to the presence of nearly
equivalent hydroxy groups and multiple chiral centers.
Carbohydrate derivatives have recently ushered in a new era
of drug development with the discovery of their role in
intercellular interactions and cell–cell communications.
Further, the nucleosides derived from modified sugars, e.g.
AZT, ddC, d4T, etc. have shown excellent antiviral activity
sugars.
selective and efficient CAL B-catalyzed acylations of
In this report, we have carried out highly
4
0
0
0
hydroxyl groups in 2-phenyl-4-(D-threo-1 ,2 ,3 -trihydroxy-
propyl)-2H-1,2,3-triazole (1), 2-phenyl-4-(D-erythro-
1 ,2 ,3 -trihydroxypropyl)-2H-1,2,3-triazole (2), 2-phenyl-
0
0
0
0
0
0
0
4-(D-arabino-1 ,2 ,3 ,4 -tetrahydroxybutyl)-2H-1,2,3-tria-
0
0
0
0
zole (3) and 2-phenyl-4-(D-lyxo-1 ,2 ,3 ,4 -tetrahydroxy-
butyl)-2H-1,2,3-triazole (4), precursors for the synthesis of
5
–8
16
and are being used as drugs.
In addition, the sugar-
triazolylacyclonucleosides using anhydrides of acetic,
modified nucleosides like LNA monomer form the back-
bone of a new therapeutic strategy called oligonucleotide
therapeutics including antigene and antisense approaches.
Multistep synthetic protocols are required to synthesize
propanoic, butanoic, pentanoic, hexanoic, heptanoic and
benzoic acids, and 2,2,2-trifluoroethyl butyrate and vinyl
acetate as acylating agents.
Keywords: lipase; Candida antarctica; butanoic anhydride; N-
phenyltriazolylsugar.
2. Results and discussion
*
Corresponding authors. Tel.: þ91-11-725-6555; fax: þ91-11-725-7206
The triazolylsugars 1–4 were prepared in two steps starting
from the corresponding sugars, i.e. D-xylose, D-ribose,
(
e-mail: virparmar@yahoo.co.in
V.S.P.); tel. þ91-11-2766-6555; fax: þ91-11-2766-7206 (A.K.P.);
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.10.059

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A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
D-glucose and D-galactose, respectively, via their conversion
into phenylosazones, followed by oxidative cyclization with
1
7–20
1
% CuSO in overall yields of 43–54% (Scheme 1).
4
The structures of these triazolyl sugar derivatives were
unambiguously established on the basis of their spectral
analysis. The melting points of all the four compounds 1–4
and spectral data of compounds 1 and 3 were found identical
1
3,16–20
with those reported in the literature,
spectral data for triazolyl sugar derivatives 2 and 4 is being
however the
reported here for the first time.
Different lipases, i.e. C. antarctica lipase B (CAL), C.
rugosa lipase (CRL) and porcine pancreatic lipase (PPL)
were screened for selective acylation of primary/secondary
hydroxyl groups in triazolyl sugar derivatives 1–4 using
propanoic anhydride as the acylating agent. Diisopropyl
ether was used as solvent in the case of screening reactions
catalyzed by CAL and CRL, whereas tetrahydrofuran was
employed as the solvent when PPL was used as the
2
,13,14
biocatalyst, based on our earlier experience.
None of
the above triazolylsugars were accepted as substrates by
CRL for propanoylation with propanoic anhydride. Both
CAL and PPL were found to transform the starting
triazolylsugars 1–4 into less polar products (as seen on
TLC) upon incubation with propanoic anhydride, however
the rate of transformation was much slower in the reaction
catalyzed by PPL than the reaction catalyzed by CAL, and
the reaction was incomplete even after 120 h (5 days) of
stirring in the former case. On the basis of the screening test,
CAL in diisopropyl ether was selected for further acylation
studies on triazolyl sugars 1–4.
In a typical reaction, a mixture of triazolyl sugar (1–4,
1
mmol) and propanoic anhydride (1 mmol) in DIPE
20 ml) was shaken with CAL (150 mg) in an incubator
(
shaker at 42–458C and the progress of the reaction was
monitored on TLC (Scheme 2). The substrates were not
soluble in DIPE initially, however the solubility increased
with the progress of the reaction. On completion of the
Scheme 2.
reaction the enzyme was filtered off and solvent was
removed under reduced pressure. The crude product thus
obtained was purified by passing through a short column of
silica gel, which afforded the acylated compound in a pure
form. It was observed that CAL in diisopropyl ether
exclusively acylates the lone primary hydroxyl group over
two secondary hydroxyl groups, in compounds 1 and 2 and
over three secondary hydroxyl groups in compounds 3 and 4
leading to the formation of propanoyl derivatives 5b–8b,
respectively, in 20–70% yields (Scheme 2, Table 1).
In order to find out the tolerance of CAL for different acid
anhydrides as acylating agents and also to find out the best
lipase-anhydride combination for selective and efficient
acylation, different acid anhydrides, e.g. acetic, butanoic,
pentanoic, hexanoic, heptanoic and benzoic anhydrides
together with propanoic anhydride have been examined for
the acylation of triazolylsugars 1–4. The C. antarctica
lipase in diisopropyl ether was found to accept all these
seven acid anhydrides as acylating agents and transfers the
acyl group exclusively at the primary hydroxyl group of
triazolylsugars over the secondary hydroxyl groups leading
to the formation of the monoacylated products 5a–5g,
6a–6g, 7a–7g and 8a–8g in 15–99% yields (Table 1).
Scheme 1.

A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
10271
a
Table 1. Regioselective acylation of triazolylsugars 1–4 mediated by CAL in diisopropyl ether at 42–458C using different acylating agents
Substrate
Acylating agent/reaction time
Product
% Yield
Trihydroxytriazole 1
Acetic anhydride/48 h
Acetyltriazole 5a
60
70
98
97
98
98
65
82
95
Propanoic anhydride/48 h
Butanoic anhydride/45 min
Pentanoic anhydride/1 h
Hexanoic anhydride/45 min
Heptanoic anhydride/1 h
Benzoic anhydride/48 h
Propanoyltriazole 5b
Butanoyltriazole 5c
Pentanoyltriazole 5d
Hexanoyltriazole 5e
Heptanoyltriazole 5f
Benzoyltriazole 5g
Butanoyltriazole 5c
Acetyltriazole 5a
2,2,2-Trifluoroethyl butyrate/4.5 h
Vinyl acetate/4 h
Trihydroxytriazole 2
Acetic anhydride /48 h
Propanoic anhydride/48 h
Butanoic anhydride /1 h
Pentanoic anhydride/7 h
Hexanoic anhydride/10 h
Heptanoic anhydride/9 h
Benzoic anhydride/48 h
Acetyltriazole 6a
50
40
99
82
83
83
54
75
95
Propanoyltriazole 6b
Butanoyltriazole 6c
Pentanoyltriazole 6d
Hexanoyltriazole 6e
Heptanoyltriazole 6f
Benzoyltriazole 6g
Butanoyltriazole 6c
Acetyltriazole 6a
2,2,2-Trifluoroethyl butyrate/7 h
Vinyl acetate/5 h
Tetrahydroxytriazole 3
Acetic anhydride/48 h
Acetyltriazole 7a
15
20
99
85
84
85
15
53
97
Propanoic anhydride/48 h
Butanoic anhydride/2.5 h
Pentanoic anhydride/10 h
Hexanoic anhydride/8 h
Heptanoic anhydride/8 h
Benzoic anhydride/48 h
Propanoyltriazole 7b
Butanoyltriazole 7c
Pentanoyltriazole 7d
Hexanoyltriazole 7e
Heptanoyltriazole 7f
Benzoyltriazole 7g
Butanoyltriazole 7c
Acetyltriazole 7a
2,2,2-Trifluoroethyl butyrate/12 h
Vinyl acetate/2.5 h
Tetrahydroxytriazole 4
Acetic anhydride/48 h
Acetyltriazole 8a
30
35
95
88
85
89
32
65
97
Propanoic anhydride/48 h
Butanoic anhydride/5 h
Pentanoic anhydride/11 h
Hexanoic anhydride/10 h
Heptanoic anhydride/14 h
Benzoic anhydride/48 h
Propanoyltriazole 8b
Butanoyltriazole 8c
Pentanoyltriazole 8d
Hexanoyltriazole 8e
Heptanoyltriazole 8f
Benzoyltriazole 8g
Butanoyltriazole 8c
Acetyltriazole 8a
2,2,2-Trifluoroethyl butyrate/10 h
Vinyl acetate/3 h
a
All these reactions when performed under identical conditions without adding the lipase yielded mixtures of acylated compounds without any selectivity
Although CAL in diisopropyl ether accepts different
aliphatic and aromatic acid anhydrides as acylating agents,
butanoic anhydride was found to be the most efficient
acylating agent among all seven anhydrides in this study on
different triazolylsugars. Thus, incubation of triazolylsugars
acylating agent beyond C may disturb the finer fitting of the
4
acylating agent in the active site of the enzyme leading to a
slight decrease in turnover and increase in the reaction time
of enzyme-catalyzed acylation reaction. The aromatic acid
anhydride, benzoic anhydride was found to be a poor
acylating agent for all four triazolylsugars.
1
–4 with CAL in diisopropyl ether and butanoic anhydride
led to the formation of corresponding mono-esters 5c, 6c, 7c
and 8c in nearly quantitative yields, i.e. 98, 99, 99 and 95%,
respectively. It is not only the yield, the acylation reaction
affected by butanoic anhydride takes minimum time as well,
e.g. the rate of monoacylation of 2-phenyl-4-(D-threo-
Among the four triazolylsugars 1–4, compound 1 was
found to be the best substrate for CAL mediated acylation
reaction with all the seven anhydrides, both in terms of the
turnover of the reaction and the average reaction time. For
example, the average turnover and the average reaction time
in case of CAL-catalyzed acylation of triazolylsugar 1 are
84% and 21.1 h, respectively, whereas the average turnover/
reaction time in case of triazolylsugars 2–4 are 70%/24.4 h,
56%/24.6 h and 64%/26.3 h, respectively.
0
0 0
1
,2 ,3 -trihydroxypropyl)-2H-1,2,3-triazole (1) mediated by
CAL in diisopropyl ether with butanoic anhydride is 64
times faster than the rate of acylation of the same substrate
with acetic anhydride (Table 1). This study indicates the
utility of butanoic, pentanoic, hexanoic and heptanoic
anhydrides as acylating agents over acetic and propanoic
anhydrides, thus indicating that the increase in lipophilicity
of the acylating agent increases the rate and turnover of the
acylation reaction catalyzed by CAL in diisopropyl ether, as
the yields of the acylation reactions with butanoic,
pentanoic, hexanoic and heptanoic anhydrides are of the
same order (Table 1). However the time taken for the
reactions with higher fatty acid anhydrides are longer,
thereby indicating that the increase of chain length of
The enzymatic reactions with CAL in DIPE on the
substrates 1–4 were also tried using 2,2,2-trifluoroethyl
butyrate and vinyl acetate, both of these acylating agents
exhibited exclusive selectivity for the primary hydroxyl
group on all the substrates like the acid anhydrides.
However, in comparison to 2,2,2-trifluoroethyl butyrate,
butanoic anhydride is a better agent for butanoylation
as yields with the former were 53–82% as compared to

10272
A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
9
5–99% with the latter (Table 1). On the other hand, vinyl
4.1. Preparation of tri- and tetrahydroxytriazolyl sugars
1–4
acetate is a better acetylating agent as compared to acetic
anhydride, as the yields with vinyl acetate were 95–97%
compared to those (15–60%) obtained with acetic
anhydride (Table 1).
The tri- and tetrahydroxytriazolyl sugars 1–4 were prepared
7–20
1
by following the literature procedures.
Thus, conden-
sation of D-xylose, D-ribose, D-glucose and D-galactose
with phenylhydrazine led to the formation of respective
phenylosazones, which upon the oxidative action of aq.
CuSO4 gave the corresponding triazolylsugars 1–4
(Scheme 1). The structures of 1–4 were established from
their spectral data. The melting points and optical rotation
values of all the four compounds and spectral data of two
known compounds 1 and 3 were found identical with those
The monoacylated triazolylsugars 5a–5g, 6a–6g, 7a–7g
and 8a–8g of this study are new compounds and have been
1
3
synthesized for the first time, except for 5a and 7a. The
structures of all these twenty eight compounds were
unambiguously established on the basis of their spectral
1
13
analysis (IR, H, C NMR and high resolution mass
1
spectra). The assignments of H NMR spectra of two
representative compounds, viz. 2-phenyl-4-(D-arabino-4 -
0
butanoyloxy-1 ,2 ,3 -trihydroxybutyl)-2H-1,2,3-triazole
13,16–18
reported in literature.
0
7c) and 2-phenyl-4-(D-lyxo-4 -propanoyloxy-1 ,2 ,3 -tri-
0
0
0
hydroxybutyl)-2H-1,2,3-triazole (8b) have also been
0
0
0
0
0
0
2H-1,2,3-triazole (2). It was obtained from D-ribose in
(
4.1.1. 2-Phenyl-4-(D-erythro-1 ,2 ,3 -trihydroxypropyl)-
1
1
19
confirmed from their H– H COSY NMR spectra.
43% yield, mp 79–808C (lit. 80–818C). R : 0.24 (chloro-
f
2
9
19
form–methanol, 9:1); [a] ¼þ20.0 (c 0.81, H O), lit.
D
2
2
0
1
[
a] ¼þ23.1 (c 0.80, H O); H NMR (300 MHz, CDCl ): d
D
2
3
0
3. Conclusions
3.26 (2H, 2 brs, 2£OH), 3.83 (2H, m, C-3 H and OH), 3.72
0 0
(
1H, d, J¼8.4 Hz, C-3 H), 4.06 (1H, brs, C-2 H), 5.08 (1H,
0 00
This study has clearly demonstrated the specificity of CAL
for the acylation of primary hydroxyl groups over the
secondary hydroxyl groups of triazolylsugars using acid
anhydrides as acylating agents. This work further reveals
that butanoic anhydride and vinyl acetate are the most
suitable acylating agents for CAL–diisopropyl ether
system. The biocatalytic route developed in this paper can
find utility for selective manipulation of multiple hydroxyl
groups in triazolyl sugar derivatives while synthesizing
bioactive molecules of this class, viz. in the synthesis of
triazolylacyclonucleosides.
d, J¼4.2 Hz, C-1 H), 7.35–7.37 (1H, m, C-4 H), 7.44–7.49
00 00
(2H, m, C-3 H and C-5 H), 7.85 (1H, s, C-5H) and 8.02
0
0
00
13
(2H, d, J¼7.9 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
0 0 0
CDCl ): d 63.34 (C-3 ), 68.39 (C-2 ), 74.48 (C-1 ), 119.16
3
0
0
00
00
00
00
(C-3 and C-5 ), 127.96 (C-4 ), 129.61 (C-2 and C-6 ),
0
0
134.59 (C-5), 139.83 (C-1 ) and 150.04 (C-4).
0
0
0
0
4.1.2. 2-Phenyl-4-(D-lyxo-1 ,2 ,3 ,4 -tetrahydroxybutyl)-
2H-1,2,3-triazole (4). It was obtained from D-galactose in
2
0
51% yield, mp 109–1108C (lit. 110–1118C). R : 0.20
f
2
D
9
(chloroform–methanol, 9:1); [a]
20
¼216.4 (c 0.20, CHCl
),
3
2
0
1
lit. [a] ¼213.3 (c 0.20, CHCl ); H NMR (300 MHz,
D
3
0
DMSO-d ): d 3.40–3.48 (3H, m, C-4 H and OH), 3.72 (1H,
6
0
4. Experimental
d, J¼8.4 Hz, C-3 H), 3.80 (1H, t, J¼6.0 Hz and 5.7 Hz,
0
0
C-2 H), 4.77 (1H, d, J¼8.4 Hz, C-1 H), 7.39 (1H, t,
0
0
00
Melting points were determined on a Mettler FP62
instrument or in a sulfuric acid bath and are uncorrected.
The IR spectra were recorded either on a Perkin–Elmer
J¼7.3 Hz, C-4 H), 7.55 (2H, d, J¼7.7 Hz, C-3 H and
00
0
C-5 H), 7.96 (1H, s, C-5H) and 7.99 (2H, d, J¼ 8.1 Hz,
0
00
(C-4 ), 66.10 (C-3 ), 70.22 (C-2 ), 72.64 (C-1 ), 118.39 (C-
13
C-2 H and C-6 H); C NMR (75.5 MHz, CDCl
): d 63.09
3
0
0
0
0
1
model 2000 FT-IR or RXI FT-IR spectrometer. The H and
1
C NMR spectra were recorded on a Bruker AC-300
00 00 00 00 00
3
3 and C-5 ), 127.57 (C-4 ), 129.99 (C-2 and C-6 ), 135.25
0
0
Avance 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
FAB-HRMS spectra of all the compounds to measure their
accurate masses were recorded on a JOEL JMS-AX505W
high resolution mass spectrometer in positive mode using
the matrix HEDS (bishydroxyethylsulfide) doped with
sodium acetate. The optical rotations were measured on a
Perkin–Elmer 241 polarimeter. The C. antarctica lipase B
immobilized on accurel was gifted by Novo Nordisk Co.
and used after storing in vacuo over P O for about
(C-5), 139.70 (C-1 ) and 153.29 (C-4).
4.2. General procedure of C. antarctica lipase-catalyzed
acylation of triazolylsugars 1–4 with acid anhydrides
To a mixture of the triazolyl sugar (1–4, 1 mmol) and dry
diisopropyl ether (20 ml), appropriate acid anhydride
(1.2 mmol) was added, followed by C. antarctica lipase B
(150 mg). The reaction mixture was stirred at 42–458C in an
incubator shaker and progress of the reaction was monitored
periodically by TLC. On completion the reaction was
stopped by filtering off the enzyme and solvent evaporated
to dryness under vacuum. The crude product thus obtained
was purified either by crystallization from a mixture of
petroleum ether–ethyl acetate or by elution with a mixture
of chloroform–methanol through a short glass column of
silica gel.
2
5
2
5–30 h. The enzymes, C. rugosa lipase (CRL, Type VII)
and porcine pancreatic lipase (PPL, Type II) were purchased
from Sigma Chemical Co. (USA) and used after storing in
vacuo over P O for 24 h. Diisopropyl ether (DIPE) was
2
5
˚
distilled over activated molecular sieves (4 A) prior to use.
Analytical TLCs were performed on pre-coated Merck
silica gel 60F254 plates; the spots were detected either
under UV light or by charring with 4% alcoholic H SO .
0
0
0
4.2.1. 2-Phenyl-4-(D-threo-3 -acetoxy-1 ,2 -dihydroxy-
propyl)-2H-1,2,3-triazole (5a). It was obtained as a white
crystalline solid (166.2 mg) in 60% yield, mp 130–1318C.
2
4
Silica gel (100–200 mesh) was used for column
chromatography.

A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
00
10273
3
0
R : 0.51 (chloroform–methanol, 9:1); [a] ¼28.0 (c 0.01,
C-5 H), 7.85 (1H, s, C-5H) and 8.03 (2H, d, J¼7.9 Hz,
f
D
1
00
(OCO(CH ) CH ), 22.20 (OCO(CH ) CH CH ), 26.96
00
13
MeOH); H NMR (300 MHz, CDCl ): d 2.09 (3H, s,
3
C-2 H and C-6 H); C NMR (75.5 MHz, CDCl ): d 13.66
3
OCOCH ), 2.99 and 3.05 (2H, 2 brs, 1H each, 2£OH),
3
2 3
3
2 2
2
3
0
0
1H, brs, C-1 H), 7.35–7.37 (1H, m, C-4 H), 7.44–7.49
4
.22–4.26 (2H, m, C-3 H), 4.30–4.32 (1H, m, C-2 H), 4.94
(OCOCH CH CH CH ), 33.89 (OCOCH (CH ) CH ),
2 2 2 3 2 2 2 3
0
2H, m, C-3 H and C-5 H), 7.85 (1H, s, C-5H) and 8.02
00
0 0 0
64.89 and 67.20 (C-2 and C-3 ), 72.35 (C-1 ), 118.93
(C-3 and C-5 ), 127.73 (C-4 ), 129.33 (C-2 and C-6 ),
(
(
(
0
0
00
00
00
00
00
00
00
00
13
00
2H, d, J¼7.9 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
134.15 (C-5), 139.66 (C-1 ), 149.27 (C-4) and 179.76
(CvO); IR (KBr): 3408 (OH), 2927, 1728 (CvO), 1176,
0
CDCl ): d 21.29 (OCOCH ), 65.56 and 67.63 (C-2 and
3
3
0
29.81 (C-2 and C-6 ), 134.60 (C-5), 140.13 (C-1 ), 149.77
0
00
00
00
21
C-3 ), 72.68 (C-1 ), 119.39 (C-3 and C-5 ), 128.21 (C-4 ),
00
1104 and 756 cm
þ
;
FAB-HRMS: m/z 342.1423
0
0
00
1
([MþNa] , C H N O Na calcd 342.1430).
1
6 21 3 4
(
C-4) and 171.77 (CvO); IR (KBr): 3345 (OH), 2928, 1743
CvO), 1598, 1500, 1373, 1310, 1230, 1124, 1038, 974 and
0
0
0
(
4.2.5. 2-Phenyl-4-(D-threo-3 -hexanoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (5e). It was obtained
as colorless oil (326 mg) in 98% yield. R : 0.58 (chloro-
2
1
FAB-HRMS: m/z 300.0988 ([MþNa]þ,
7
C H N O Na calcd 300.0960).
57 cm
;
1
3
15
3
4
f
2
2
1
form–methanol, 9:1); [a] ¼220.0 (c 0.01, MeOH); H
D
0
0
0
hydroxypropyl)-2H-1,2,3-triazole (5b). It was obtained
4
.2.2. 2-Phenyl-4-(D-threo-3 -propanoyloxy-1 ,2 -di-
NMR (300 MHz, CDCl ): d 0.88 (3H, t, J¼6.6 Hz,
3
OCO(CH ) CH ), 1.28–1.31 (4H, m, OCO(CH ) CH CH -
2
4
3
2 2
2
2
as a white crystalline solid (203 mg) in 70% yield, mp 110–
2
CH ), 1.59–1.67 (2H, m, OCOCH CH (CH ) CH ), 2.33
3 2 2 2 2 3
2
D
1
128C. R : 0.54 (chloroform–methanol, 9:1); [a] ¼225.4
(2H, t, J¼7.4 Hz, OCOCH (CH ) CH ), 3.19 (2H, 2 brs, 1H
f
2
2 3
3
1
0
0
(
c 0.01, MeOH); H NMR (300 MHz, CDCl ): d 1.15 (3H, t,
3
each, 2£OH), 4.18–4.34 (3H, m, C-2 H and C-3 H), 4.93
0 00
(1H, brs, C-1 H), 7.32–7.36 (1H, m, C-4 H), 7.44–7.49
J¼7.3 Hz, OCOCH CH ), 2.34–2.42 (2H, q, J¼7.3 Hz,
2
3
00 00
(2H, m, C-3 H and C-5 H), 7.84 (1H, s, C-5H) and 8.02
OCOCH CH ), 2.98 and 3.03 (2H, 2 brs, 1H each, 2£OH),
2
3
0
0
1H, brs, C-1 H), 7.32–7.37 (1H, m, C-4 H), 7.45–7.50
00
CDCl ): d 13.88 (OCO(CH ) CH ), 22.28 (OCO(CH ) -
00
13
4
.23–4.28 (2H, m, C-3 H), 4.31–4.36 (1H, m, C-2 H), 4.94
(2H, d, J¼7.8 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
0
0
0
(
(
(
3
2 4
3
2 3
0
0
00
2H, m, C-3 H and C-5 H), 7.85 (1H, s, C-5H) and 8.02
00
CH CH ), 24.57 (OCO(CH ) CH CH CH ), 31.28
2 3 2 2 2 2 3
00
13
2H, d, J¼7.9 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
(OCOCH CH (CH ) CH ), 34.13 (OCOCH (CH ) CH ),
3
2
2
2 2
3
2
2 3
0
and C-5 ), 127.71 (C-4 ), 129.32 (C-2 and C-6 ), 134.14
0
0
00
CDCl ): d 9.03 (OCOCH CH ), 27.45 (OCOCH CH ),
3
64.88 and 67.19 (C-2 and C-3 ), 72.30 (C-1 ), 118.90 (C-3
3
2
3
2
0
and C-5 ), 127.72 (C-4 ), 129.32 (C-2 and C-6 ), 134.12
0
0
00
00
00
00
00
(C-5), 139.65 (C-1 ), 149.33 (C-4) and 174.23 (CvO); IR
6
4.97 and 67.17 (C-2 and C-3 ), 72.28 (C-1 ), 118.90 (C-3
0
0
00
00
00
C-5), 139.65 (C-1 ), 149.28 (C-4) and 174.80 (CvO); IR
00
(KBr): 3413 (OH), 2957, 2931, 1737 (CvO), 1498, 1173,
0
0
KBr): 3352 (OH), 2926, 1751 (CvO), 1499, 1182, 975 and
(
(
968 and 757 cm2 ; FAB-HRMS: m/z 356.1590 ([MþNa] ,
1
þ
2
1
FAB-HRMS: m/z 314.1146 ([MþNa]þ,
7
C H N O Na calcd 314.1117).
53 cm
;
C H N O Na calcd 356.1586).
17 23 3 4
1
4 17 3 4
0 0 0
.2.6. 2-Phenyl-4-(D-threo-3 -heptanoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (5f). It was obtained as
4
0
hydroxypropyl)-2H-1,2,3-triazole (5c). It was obtained
0
0
4
.2.3. 2-Phenyl-4-(D-threo-3 -butanoyloxy-1 ,2 -di-
colorless oil (340 mg) in 98% yield. R : 0.60 (chloroform–
f
2
2
1
as a white solid (298 mg) in 98% yield, mp 908C. R : 0.56
f
methanol, 9:1); [a] ¼222.6 (c 0.01, MeOH); H NMR
D
2
2
(
MeOH); H NMR (300 MHz, CDCl ): d 0.95 (3H, t,
chloroform–methanol, 9:1); [a] ¼217.2 (c 0.01,
(300 MHz, CDCl ): d 0.87 (3H, brs, OCO(CH ) CH ),
3
D
3
2 5
1
1.25–1.28 (6H, m, OCO(CH ) (CH ) CH ), 1.60–1.64
2 2 2 3 3
3
J¼7.4 Hz, OCO(CH ) CH ), 1.63–1.70 (2H, m, OCOCH -
(2H, m, OCOCH CH (CH ) CH ), 2.34 (2H, t, J¼7.4 Hz,
0
OCOCH (CH ) CH ), 4.22–4.35 (3H, m, C-2 H and
2 2 4 3
2
2
3
2
2
2
2 3
3
CH CH ), 2.34 (2H, t, J¼7.4 Hz, OCOCH CH CH ), 4.23–
2
3
2
2
3
0
brs, C-1 H), 7.35–7.38 (1H, m, C-4 H), 7.45–7.50 (2H, m,
0
0 0 00
C-3 H), 4.95 (1H, brs, C-1 H), 7.32–7.37 (1H, m, C-4 H),
4
.28 (2H, m, C-3 H), 4.33–4.36 (1H, m, C-2 H), 4.95 (1H,
0
C-3 H and C-5 H), 7.86 (1H, s, C-5H) and 8.01–8.05 (2H,
00
00 00
7.44–7.49 (2H, m, C-3 H and C-5 H), 7.85 (1H, s, C-5H)
00
00
m, C-2 H and C-6 H); C NMR (75.5 MHz, CDCl ): d
00
(75.5 MHz, CDCl ): d 14.35 (OCO(CH ) CH ), 22.82
00
13
and 8.02 (2H, d, J¼8.0 Hz, C-2 H and C-6 H); C NMR
0
0
00
2.87 (OCO(CH ) CH ), 17.62 (OCOCH CH CH ), 35.27
13
3
3
2 5
3
1
(
(
(OCO(CH ) CH CH ), 25.22 (OCO(CH ) CH CH CH ),
2 4 2 3 2 3 2 2 3
29.15 (OCO(CH ) CH (CH ) CH ), 31.78 (OCOCH CH -
2 2 2 2 2 3 2 2
2
2
3
2
2
3
0
0
C-1 ), 118.14 (C-3 and C-5 ), 126.96 (C-4 ), 128.56 (C-2
OCOCH CH CH ), 64.10 and 66.43 (C-2 and C-3 ), 71.54
2
2
3
00
0
00
00
00
and C-6 ), 133.38 (C-5), 138.89 (C-1 ), 148.56 (C-4) and
(CH ) CH ), 34.54 (OCOCH (CH ) CH ), 65.24 and 67.56
2
3
3
2
2 4
3
0
0
00
73.28 (CvO); IR (KBr): 3433 (OH), 2926, 1727 (CvO),
0
0
0
00
00
128.08 (C-4 ), 129.68 (C-2 and C-6 ), 134.50 (C-5), 140.02
(C-2 and C-3 ), 72.68 (C-1 ), 119.27 (C-3 and C-5 ),
0
0
00
00
(C-1 ), 149.66 (C-4) and 174.59 (CvO); IR (KBr): 3415
1
1
3
2
1
00
(OH), 2928, 1726 (CvO), 1498, 1169, 968 and 756 cm
500, 1462, 1103, 967 and 752 cm ; FAB-HRMS: m/z
þ
21
28.1289 ([MþNa] , C H N O Na calcd 328.1273).
;
1
5 19 3 4
þ
FAB-HRMS: m/z 370.1767 ([MþNa] , C H N O Na
1
8 25 3 4
0
hydroxypropyl)-2H-1,2,3-triazole (5d). It was obtained
0
0
4
.2.4. 2-Phenyl-4-(D-threo-3 -pentanoyloxy-1 ,2 -di-
calcd 370.1743).
0
0
0
as colorless oil (309 mg) in 97% yield. R : 0.57 (chloro-
f
4.2.7. 2-Phenyl-4-(D-threo-3 -benzoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (5g). It was obtained
as a white crystalline solid (220 mg) in 65% yield, mp 137–
2
2
1
form–methanol, 9:1); [a] ¼29.6 (c 0.01, MeOH); H
D
NMR (300 MHz, CDCl ): d 0.91 (3H, t, J¼7.3 Hz,
3
3
0
OCO(CH ) CH ), 1.31–1.41 (2H, m, OCO (CH ) CH -
2
1388C. R : 0.57 (chloroform–methanol, 9:1); [a] ¼223.0
3
3
2 2
2
f
D
1
CH ), 1.57–1.67 (2H, m, OCOCH CH CH CH ), 2.35 (2H,
3
(c 0.01, MeOH); H NMR (300 MHz, DMSO-d ): d 4.09
6
2
2
2
3
0
each, C-3 H and C-3 H ), 4.93 (1H, brs, C-1 H), 5.33 and
t, J¼7.5 Hz, OCOCH (CH ) CH ), 4.22–4.28 (2H, m,
(1H, brs, C-2 H), 4.24–4.30 and 4.36–4.42 (2H, 2m, 1H
0
2
2 2
3
0
.33–7.37 (1H, m, C-4 H), 7.45–7.50 (2H, m, C-3 H and
0
0
0
0
C-3 H), 4.31–4.36 (1H, m, C-2 H), 4.94 (1H, brs, C-1 H),
7
a
b
00
00
5.73 (2H, 2 brs, 1H each, 2£OH), 7.36–7.95 (10H, m,

10274
A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
1
3
(CvO), 1462, 1185, 1058 and 756 cm21; FAB-HRMS: m/z
Ar-H) and 8.02 (1H, s, C-5H); C NMR (75.5 MHz,
0
0
0
þ
DMSO-d ): d 66.77 and 68.01 (C-2 and C-3 ), 72.23 (C-1 ),
6
19.19, 128.43, 129.54, 129.64, 130.19, 130.26, 130.64,
30.76, 133.85, 134.25, 136.15, 140.27, 152.50 (aromatic
328.1290 ([MþNa] , C H N O Na calcd 328.1273).
15 19
3
4
1
1
0
0
0
4.2.11. 2-Phenyl-4-(D-erythro-3 -pentanoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (6d). It was obtained
as a white solid (261 mg) in 82% yield, mp 53–548C. R :
carbons, C-4 and C-5) and 166.67 (CvO); IR (KBr): 3330
1
2
(
OH), 2925, 1720 (CvO), 1271, 1130 and 712 cm ; FAB-
þ
f
22
HRMS: m/z 362.1129 ([MþNa] , C H N O Na calcd
0.56 (chloroform–methanol, 9:1); [a] ¼þ25.8 (c 0.01,
1
8
17
3
4
D
1
3
62.1117).
MeOH); H NMR (300 MHz, CDCl ): d 0.90 (3H, t,
3
J¼7.5 Hz, OCO(CH ) CH ), 1.32–1.34 (2H, m,
OCO(CH ) CH CH ), 1.60 (2H, brs, OCOCH CH CH -
2 2 2 3 2 2 2
CH ), 2.34 (2H, brs, OCOCH (CH ) CH ), 3.12–3.24 (2H,
3 2 2 2 3
2
3
3
0
0
0
propyl)-2H-1,2,3-triazole (6a). It was obtained as a white
4
.2.8. 2-Phenyl-4-(D-erythro-3 -acetoxy-1 ,2 -dihydroxy-
crystalline solid (138 mg) in 50% yield, mp 85–878C. R :
f
brs, 2£OH), 4.19–4.35 (3H, m, 2H and 1H each,
2
2
0
0
0
0
MeOH); H NMR (300 MHz, CDCl ): d 2.10 (3H, s,
.52 (chloroform–methanol, 9:1); [a] ¼þ15.8 (c 0.01,
respectively, C-3 H and C-2 H), 4.94 (1H, s, C-1 H), 7.35
D
1
00 00 00
(1H, m, C-4 H), 7.47 (2H, brs, C-3 H and C-5 H), 7.86 (1H,
3
0
(75.5 MHz, CDCl ): d 12.90 (OCO(CH ) CH ), 21.47
0
00
13
OCOCH ), 3.06–3.13 (2H, 2brs, 1H each, 2£OH), 4.20–
s, C-5H) and 8.02 (2H, brs, C-2 H and C-6 H); C NMR
3
0
0
0
4
(
.40 (3H, m, C-2 H and C-3 H), 4.96 (1H, brs, C-1 H), 7.35
3
2 3
3
0
0
00
1H, t, J¼7.26 Hz, C-4 H), 7.47 (2H, t, J¼7.71 Hz, C-3 H
(OCO(CH ) CH CH ), 26.19 (OCOCH CH CH CH ),
2 2 2 3 2 2 2 3
0
C-2 H and C-6 H); C NMR (75.5 MHz, CDCl ): d 21.18
0
0
33.12 (OCOCH (CH ) CH ), 64.16 and 66.93 (C-2 and
2 2 2 3
and C-5 H), 7.86 (1H, s, C-5H) and 8.03 (2H, t, J¼7.99 Hz,
0
OCOCH ), 65.50 and 68.08 (C-2 and C-3 ), 73.35 (C-1 ),
0
00
13
0 0 00 00 00
C-3 ), 72.28 (C-1 ), 118.11 (C-3 and C-5 ), 126.95 (C-4 ),
128.57 (C-2 and C-6 ), 133.48 (C-5), 139.30 (C-1 ), 148.39
3
0
19.25 (C-3 and C-5 ), 128.10 (C-4 ), 129.70 (C-2 and
0
0
00
00
00
(
1
3
0
0
00
00
00
C-6 ), 134.59 (C-5), 139.98 (C-1 ), 149.48 (C-4) and 172.13
(C-4) and 173.95 (CvO); IR (KBr): 3342 (OH), 2931, 1739
21
0
CvO); IR (KBr): 3342 (OH), 2903, 1740 (CvO), 1250,
0
00
(CvO), 1498, 1182, 971 and 757 cm ; FAB-HRMS: m/z
þ
(
1
(
342.1454 ([MþNa] , C H N O Na calcd 342.1430).
1
6 21 3 4
2
1
055 and 766 cm
þ
;
FAB-HRMS: m/z 300.0976
0
0
0
[MþNa] , C H N O Na calcd 300.0960).
4.2.12. 2-Phenyl-4-(D-erythro-3 -hexanoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (6e). It was obtained
as a white crystalline solid (276 mg) in 83% yield, mp 58–
1
3 15 3 4
0 0 0
hydroxypropyl)-2H-1,2,3-triazole (6b). It was obtained
as a white crystalline solid (116 mg) in 40% yield, mp 86–
4
.2.9. 2-Phenyl-4-(D-erythro-3 -propanoyloxy-1 ,2 -di-
2
2
598C. R : 0.59 (chloroform–methanol, 9:1); [a] ¼þ21.4 (c
f
D
1
0.01, MeOH); H NMR (300 MHz, CDCl ): d 0.88 (3H, t,
3
2
2
8
0
88C. R : 0.55 (chloroform–methanol, 9:1); [a] ¼þ26.6 (c
J¼7.4 Hz, OCO(CH ) CH ), 1.28 (4H, brs, OCO(CH ) -
(CH ) CH ), 1.61 (2H, brs, OCOCH CH (CH ) CH ), 2.32
2 2 3 2 2 2 2 3
f
D
2 4
3
2 2
1
.01, MeOH); H NMR (300 MHz, CDCl ): d 1.13 (3H, t,
3
J¼7.4 Hz, OCOCH CH ), 2.33–2.40 (2H, m, OCOCH -
(2H, t, J¼7.3 Hz, OCOCH (CH ) CH ), 2.93 (2H, brs,
2
3
2
2
2 3
3
CH ), 3.20 (2H, 2 brs, 1H each, 2£OH), 4.19–4.40 (3H, 2m,
2£OH), 4.19–4.39 (3H, m, 2H and 1H each, respectively,
3
0
0
0
0
0
2
H and 1H each, C-3 H and C-2 H), 4.95 (1H, d, J¼5.4 Hz,
C-3 H and C-2 H), 4.95 (1H, d, J¼5.3 Hz, C-1 H), 7.34–
0
00
00
00
00
C-1 H), 7.34 (1H, t, J¼7.1 Hz, C-4 H), 7.47 (2H, t,
7.36 (1H, m, C-4 H), 7.44–7.49 (2H, m, C-3 H and C-5 H),
0
0
00
00
J¼7.4 Hz, C-3 H and C-5 H), 7.86 (1H, s, C-5H) and
7.86 (1H, s, C-5H) and 8.01 (2H, d, J¼7.7 Hz, C-2 H and
00
00
75.5 MHz, CDCl ): 8.83 (OCOCH CH ), 27.43
13
00
13
8
.01 (2H, d, J¼7.8 Hz, C-2 H and C-6 H); C NMR
C-6 H);
C
NMR (75.5 MHz, CDCl ):
3
d
12.36
(
(
(
d
OCOCH CH ), 64.92 and 67.83 (C-2 and C-3 ), 72.86
(OCO(CH ) CH ), 20.76 (OCO(CH ) CH CH ), 23.06
2 4 3 2 3 2 3
3
2
3
0
C-1 ), 118.90 (C-3 and C-5 ), 127.69 (C-4 ), 129.32 (C-2
0
(OCO(CH ) CH CH CH ),
29.75
(CH ) CH ), 32.62 (OCOCH (CH ) CH ), 63.41 and
(OCOCH CH
2 2
2
3
2 2
2
2
3
0
00
00
00
00
2
2
3
2
2 3
3
0
75.31 (CvO); IR (KBr): 3329 (OH), 2905, 1741 (CvO),
0
00
0 0 0 00
and C-6 ), 134.36 (C-5), 139.60 (C-1 ), 149.14 (C-4) and
66.21 (C-2 and C-3 ), 71.52 (C-1 ), 117.36 (C-3 and
C-5 ), 126.19 (C-4 ), 127.81 (C-2 and C-6 ), 132.73 (C-5),
00
0
0
00
00
00
138.11 (C-1 ), 147.65 (C-4) and 173.18 (CvO); IR (KBr):
1
1
3
2
1
498, 1192, 1057 and 759 cm ; FAB-HRMS: m/z
þ
14.1151 ([MþNa] , C H N O Na calcd 314.1117).
3341 (OH), 2931, 1741 (CvO), 1498, 1180, 1056 and
1
4 17 3 4
2
1
FAB-HRMS: m/z 356.1595 ([MþNa]þ,
C H N O Na calcd 356.1586).
17 23 3 4
757 cm
;
0
hydroxypropyl)-2H-1,2,3-triazole (6c). It was obtained
0
0
4
.2.10. 2-Phenyl-4-(D-erythro-3 -butanoyloxy-1 ,2 -di-
0
0
0
as a white solid (301 mg) in 99% yield, mp 135–1378C. R :
f
4.2.13. 2-Phenyl-4-(D-erythro-3 -heptanoyloxy-1 ,2 -di-
hydroxypropyl)-2H-1,2,3-triazole (6f). It was obtained as
a white solid (288 mg) in 83% yield, mp 68–708C. R : 0.60
2
2
0
MeOH); H NMR (300 MHz, CDCl ): d 0.88 (3H, t,
.56 (chloroform–methanol, 9:1); [a] ¼þ13.8 (c 0.01,
D
1
3
f
2
2
J¼7.4 Hz, OCO(CH ) CH ), 1.53–1.65 (2H, m, OCOCH -
(chloroform–methanol, 9:1); [a] ¼þ17.9 (c 0.01, MeOH);
2
2
3
2
D
1
CH CH ), 2.27 (2H, t, J¼7.4 Hz, OCOCH CH CH ), 3.00
H NMR (300 MHz, CDCl ): d 0.87 (3H, t, J¼7.4 Hz,
2
3
2
2
3
3
0
(
4
4
2H, 2 brs, 1H each, 2£OH), 4.08–4.13 (1H, m, C-3 H ),
OCO(CH ) CH ), 1.27 (6H, brs, OCOCH CH (CH ) CH ),
3
a/b
2 5
3
2
2
2 3
0
.17–4.22 (1H, dd, J¼11.9 and 3.3 Hz, C-3 H ), 4.30–
1.60 (2H, brs, OCOCH CH (CH ) CH ), 2.33 (2H, t,
2 2 2 3 3
b/a
0
.36 (1H, dd, J¼11.9 and 5.7 Hz, C-2 H), 4.87 (1H, d,
J¼7.3 Hz, CH OCOCH (CH ) CH ), 3.30 (2H, brs,
2
2
2 4
3
0
00
J¼5.9 Hz, C-1 H), 7.28 (1H, t, J¼7.3 Hz, C-4 H), 7.41 (2H,
2£OH), 4.19–4.40 (3H, m, 2H and 1H each, respectively,
0 0 0
0
0
00
t, J¼8.1 Hz, C-3 H and C-5 H), 7.79 (1H, s, C-5H) and 7.95
C-3 H and C-2 H), 4.95 (1H, d, J¼5.0 Hz, C-1 H), 7.32–
00 00 00
7.37 (1H, m, C-4 H), 7.44–7.49 (2H, m, C-3 H and C-5 H),
0
0
00
CDCl ): d 12.60 (OCO(CH ) CH ), 17.37 (OCOCH CH -
13
(
2H, d, J¼7.8 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
0
0
7.86 (1H, s, C-5H) and 8.02 (2H, d, J¼7.7 Hz, C-2 H and
14.02
(OCO(CH ) CH ), 22.48 (OCO(CH ) CH CH ), 24.88
3
2 2
3
2
2
0
C-3 ), 72.05 (C-1 ), 117.86 (C-3 and C-5 ), 126.96 (C-4 ),
00
13
CH ), 35.00 (OCOCH CH CH ), 63.89 and 66.68 (C-2 and
3
C-6 H);
C
NMR (75.5 MHz, CDCl ):
d
3
2
2
3
0
28.31 (C-2 and C-6 ), 133.21 (C-5), 138.60 (C-1 ), 148.13
0
00
00
00
2
5
3
2 4
2
3
0
C-4) and 173.47 (CvO); IR (KBr): 3406 (OH), 2927, 1740
0
00
00
1
(
(OCO(CH ) CH CH CH ),
28.80
(CH ) CH ), 31.43 (OCOCH CH (CH ) CH ), 34.20
(OCO(CH ) CH
2 2 2
2
3
2
2
3
2
2
3
2
2
2 3
3

A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
10275
0
3.05 (C-1 ), 118.89 (C-3 and C-5 ), 127.71 (C-4 ), 129.35
0
(
7
(
OCOCH (CH ) CH ), 64.94 and 67.77 (C-2 and C-3 ),
2
white crystalline solid (331 mg) in 99% yield, mp 110–
22
2 4
3
0
00
00
00
C-2 and C-6 ), 134.29 (C-5), 139.65 (C-1 ), 149.22 (C-4)
1128C. R : 0.53 (chloroform–methanol, 9:1); [a] ¼243.9
f
D
00
00
and 174.70 (CvO); IR (KBr): 3340 (OH), 2928, 1740
00
1
(c 0.01, MeOH); H NMR (300 MHz, CDCl ): d 0.87 (3H, t,
3
J¼7.4 Hz, OCO(CH ) CH ), 1.54–1.61 (2H, m, OCOCH -
2
2
3
2
2
1
(
3
CvO), 1177, 1055 and 757 cm ; FAB-HRMS: m/z
þ
CH CH ), 2.26 (2H, t, J¼7.4 Hz, OCOCH CH CH ), 3.88–
0 0
3.91 (1H, m, C-2 H), 3.99–4.01 (1H, brs, C-3 H), 4.24–4.30
2
3
2
2
3
70.1744 ([MþNa] , C H N O Na calcd 370.1743).
1
8 25 3 4
0 0
1H, m, C-4 H ), 4.36–4.41 (1H, m, C-4 H ), 5.23 (1H, brs,
a b
(
0
hydroxypropyl)-2H-1,2,3-triazole (6g). It was obtained
0
0
0 00
C-1 H), 7.25–7.30 (1H, m, C-4 H), 7.37–7.42 (2H, m,
4
.2.14. 2-Phenyl-4-(D-erythro-3 -benzoyloxy-1 ,2 -di-
00 00
C-3 H and C-5 H), 7.85 (1H, s, C-5H) and 7.92 (2H, d,
0
0
CDCl ): d 13.49 (OCO(CH ) CH ), 18.25 (OCOCH CH -
00
13
as a white crystalline solid (183 mg) in 54% yield, mp 65–
J¼7.6 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
2
2
6
0
78C. R : 0.59 (chloroform–methanol, 9:1); [a] ¼þ10.9 (c
f
D
3
2 2
3
2
2
1
0
C-4 ), 70.42 (C-3 ), 73.11 (C-1 ), 118.74 (C-3 and C-5 ),
.01, MeOH); H NMR (300 MHz, CDCl ): d 4.35 (1H, brs,
3
C-2 H), 4.46–4.61 (2H, m, C-3 H), 5.07 ((1H, brs, C-1 H),
.27–7.49 (6H, m, Ar-H), 7.86 (1H, s, C-5H) and 7.94–7.96
4H, m, Ar-H); C NMR (75.5 MHz, CDCl ): d 67.37 and
3
9.82 (C-2 and C-3 ), 74.93 (C-1 ), 120.76, 129.54, 130.31,
31.17, 131.40, 131.64, 135.21, 136.21, 141.48, 151.09
CH ), 35.92 (OCOCH CH CH ), 65.93 and 66.17 (C-2 and
3
2
2
3
0
0
0
0
0
0
00
00
127.54 (C-4 ), 129.18 (C-2 and C-6 ), 134.26 (C-5), 139.49
0
(C-1 ), 150.06 (C-4) and 174.58 (CvO); IR (KBr): 3442
0
00
00
7
1
3
00
(OH), 2966, 1711 (CvO), 1453, 1192, 964 and 750 cm
(
6
1
(
0
0
0
21
;
þ
FAB-HRMS: m/z 358.1382 ([MþNa] , C H N O Na
1
6
21
3
5
aromatic carbons, C-4 and C-5) and 169.15 (CvO); IR
KBr): 3339 (OH), 2923, 1721 (CvO), 1271, 1112, 1049
calcd 358.1379).
(
2
1
þ
0
0
0
0
and 713 cm ; FAB-HRMS: m/z 362.1154 ([MþNa] ,
4.2.18. 2-Phenyl-4-(D-arabino-4 -pentanoyloxy-1 ,2 ,3 -
trihydroxybutyl)-2H,1,2,3-triazole (7d). It was obtained
as a white solid (296 mg) in 85% yield, mp 101.5–102.58C.
C H N O Na calcd 362.1117).
18 17 3 4
0
0
0
hydroxybutyl)-2H-1,2,3-triazole (7a). It was obtained as
0
22
4
.2.15. 2-Phenyl-4-(D-arabino-4 -acetoxy-1 ,2 , 3 -tri-
R : 0.54 (chloroform–methanol, 9:1); [a] ¼220.0 (c 0.01,
f
D
1
MeOH); H NMR (300 MHz, CDCl ): d 0.90 (3H, t,
3
a white crystalline solid (46 mg) in 15% yield, mp 111–
2
J¼7.4 Hz, OCO(CH ) CH ), 1.34 (2H, brs, OCO(CH ) -
2
3
3
2 2
2
D
1
138C. R : 0.49 (chloroform–methanol, 9:1); [a] ¼210.7
CH CH ), 1.61 (2H, brs, OCOCH CH CH CH ), 2.37 (2H,
2 3 2 2 2 3
f
1
(
OCOCH ), 2.91–3.19 (3H, brs, 3 x OH), 3.97 (1H, brs,
c 0.01, MeOH); H NMR (300 MHz, CDCl ): d 2.12 (3H, s,
brs, OCOCH (CH ) CH ), 3.16–3.40 (3H, 2 brs, 2H and
2 2 2 3
3
0
1H, respectively, 3£OH), 3.95–4.02 (2H, m, C-2 H and
0 0 0
C-3 H), 4.37–4.43 (2H, m, C-4 H), 5.26 (1H, s, C-1 H), 7.35
3
0
.44–4.47 (1H, m, C-4 H ), 5.26 (1H, s, C-1 H), 7.33–7.37
0
0
C-2 H), 4.03 (1H, brs, C-3 H), 4.36–4.38 (1H, m, C-4 H ),
a
0
1H, m, C-4 H), 7.45–7.50 (2H, m, C-3 H and C-5 H), 7.87
0
00 00 00
(1H, brs, C-4 H), 7.46 (2H, brs, C-3 H and C-5 H), 7.87
4
(
(
b
0
0
00
00
00
NMR (75.5 MHz, CDCl ): d 12.91 (OCO(CH ) CH ),
00
13
(1H, brs, C-5H) and 8.00 (2H, brs, C-2 H and C-6 H);
C
00
1H, s, C-5H) and 8.02 (2H, d, J¼7.86 Hz, C-2 H and
3
2 3
3
0
0
13
C-6 H); C NMR (75.5 MHz, CDCl ): d 22.60 (OCOCH ),
3
21.47 (OCO(CH ) CH CH ), 26.21 (OCOCH CH CH -
2 2 2 3 2 2 2
3
0
20.65 (C-3 and C-5 ), 129.48 (C-4 ), 131.09 (C-2 and
0
0
0
0
CH ), 33.15 (OCOCH (CH ) CH ), 65.38 and 65.63 (C-2
and C-4 ), 69.98 (C-3 ), 72.23 (C-1 ), 118.10 (C-3 and
6
1
8.10 and 68.20 (C-2 and C-4 ), 72.48 (C-3 ), 74.73 (C-1 ),
0
3
2
2 2
3
0
00
00
00
0 0 0 00
00
00
CvO); IR(KBr): 3428 (OH), 2924, 1707 (CvO), 1284,
00 00 00 00
C-5 ), 126.94 (C-4 ), 128.57 (C-2 and C-6 ), 133.59 (C-5),
138.86 (C-1 ), 149.38 (C-4) and 174.15 (CvO); IR (KBr):
C-6 ), 136.08 (C-5), 141.07 (C-1 ), 151.85 (C-4) and 173.67
(
00
2
1
21
1
092, 1039 and 753 cm ; FAB-HRMS: m/z 330.1086
þ
3448 (OH), 2958, 1720 (CvO), 1187, 1095 and 752 cm
þ
calcd 372.1535).
;
(
[MþNa] , C H N O Na calcd 330.1066).
FAB-HRMS: m/z 372.1565 ([MþNa] , C H N O Na
17 23 3 5
1
4
17
3
5
0 0 0 0
trihydroxybutyl)-2H-1,2,3-triazole (7b). It was obtained
4
.2.16. 2-Phenyl-4-(D-arabino-4 -propanoyloxy-1 ,2 ,3 -
0
0
0
0
4.2.20. 2-Phenyl-4-(D-arabino-4 -hexanoyloxy-1 ,2 ,3 -tri-
hydroxybutyl)-2H,1,2,3-triazole (7e). It was obtained as a
white solid (305 mg) in 84% yield, mp 104–105.28C. R :
as a white solid (64 mg) in 20% yield, mp 109–1108C. R :
f
3
0
0
MeOH); H NMR (300 MHz, CDCl ): d 1.17 (3H, t,
.51 (chloroform–methanol, 9:1); [a] ¼233.1 (c 0.01,
D
f
1
22
0.55 (chloroform–methanol, 9:1); [a] ¼221.9 (c 0.01,
3
D
1
J¼7.5 Hz, OCOCH CH ), 2.37–2.45 (2H, q, J¼7.5 Hz,
MeOH); H NMR (300 MHz, CDCl ): d 0.88 (3H, t,
3
2
3
OCOCH CH ), 2.85 (1H, brs, OH), 3.02 and 3.10 (2H, 2
2
J¼6.6 Hz, OCO(CH ) CH ), 1.30 (4H, brs, OCO(CH ) -
3
2 4
3
2 2
0
0
brs, 2£OH), 3.95–4.03 (2H, m, C-2 H and C-3 H), 4.34–
(CH ) CH ), 1.61–1.66 (2H, m, OCOCH CH (CH ) CH ),
2 2 3 2 2 2 2 3
0
1H, m, C-4 H ), 5.27 (1H, brs, C-1 H), 7.33–7.38 (1H, m,
4
(
.40 (1H, dd, J¼12.0 Hz and 5.5 Hz, C-4 H ), 4.45–4.49
2.37 (2H, t, J¼7.5 Hz, OCOCH (CH ) CH ), 3.93–3.96
a
2
2 3
3
0
0
0
m, C-4 H ), 4.43–4.48 (1H, m, C-4 H ), 5.27 (1H, brs,
0
(1H, m, C-2 H), 4.02–4.04 (1H, m, C-3 H), 4.33–4.39 (1H,
b
0
0
00
00
0
0
C-1 H), 7.32–7.37 (1H, m, C-4 H), 7.45–7.50 (2H, m,
C-4 H), 7.48 (2H, t, J¼7.6 Hz, C-3 H and C-5 H), 7.88
a
b
00
0
0
0
(
C-6 H); C NMR (75.5 MHz, CDCl ): d 9.07 (OCOCH -
1H, s, C-5H) and 8.03 (2H, d, J¼7.6 Hz, C-2 H and
00
13
00 00
C-3 H and C-5 H), 7.87 (1H, s, C-5H) and 8.01 (2H, d,
3
2
0
C-4 ), 70.91 (C-3 ), 72.96 (C-1 ), 118.90 (C-3 and C-5 ),
00
CDCl ): d 13.13 (OCO(CH ) CH ), 21.54 (OCO(CH ) -
00
13
CH ), 27.51 (OCOCH CH ), 66.28 and 66.52 (C-2 and
3
J¼8.0 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
2
3
0
0
0
27.73 (C-4 ), 129.35 (C-2 and C-6 ), 134.33 (C-5), 139.60
00
00
3
2 4
3
2 3
0
0
00
00
1
(
(
CH CH ), 23.85 (OCO(CH ) CH CH CH ), 30.52
2 3 2 2 2 2 3
00
C-1 ), 150.14 (C-4) and 177.05 (CvO); IR (KBr): 3446
OH), 2924, 1718 (CvO), 1459, 1198, 1094, 964 and
(OCOCH CH (CH ) CH ), 33.41 (OCOCH (CH ) CH ),
3
2
2
2 2
3
2
2 3
0
118.12 (C-3 and C-5 ), 126.96 (C-4 ), 128.58 (C-2 and
0
0
0
65.39 and 65.65 (C-2 and C-4 ), 70.03 (C-3 ), 72.17 (C-1 ),
00
2
1
FAB-HRMS: m/z 344.1256 ([MþNa]þ,
00
00
00
7
C H N O Na calcd 344.1222).
48 cm
;
0
0
00
C-6 ), 133.59 (C-5), 138.85 (C-1 ), 149.36 (C-4) and 174.19
CvO); IR (KBr): 3437 (OH), 2953, 1721 (CvO), 1183,
1
5 19 3 5
(
1043 and 751 cm
0
hydroxybutyl)-2H-1,2,3-triazole (7c). It was obtained as a
0
0
0
21
4
.2.17. 2-Phenyl-4-(D-arabino-4 -butanoyloxy-1 ,2 ,3 -tri-
;
FAB-HRMS: m/z 386.1720
þ
([MþNa] , C H N O Na calcd 386.1692).
1
8 25 3 5

10276
A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
0
trihydroxybutyl)-2H-1,2,3-triazole (7f). It was obtained
0
0
0
22
4
.2.21. 2-Phenyl-4-(D-arabino-4 -heptanoyloxy-1 ,2 ,3 -
1128C. R : 0.50 (chloroform–methanol, 9:1); [a] ¼210.4
f
D
1
(c 0.01, MeOH); H NMR (300 MHz, CDCl ): d 1.13 (3H, t,
3
as a white solid (320.5 mg) in 85% yield, mp 106.6–
2
J¼7.4 Hz, OCOCH CH ), 2.32–2.40 (2H, m, OCOCH -
2
3
2
2
D
1
07.68C. R : 0.58 (chloroform–methanol, 9:1); [a] ¼
CH ), 3.07 and 3.12 (2H, brs, 2£OH), 3.33 (1H, brs, OH),
f
3
1
0
0
2
15.3 (c 0.01, MeOH); H NMR (300 MHz, CDCl ): d
3
3.93 (1H, brs, C-2 H), 4.16 (1H, brs, C-3 H), 4.22–4.34 (2H,
0
0
0
.86 (3H, brs, OCO(CH ) CH ), 1.27 (6H, brs,
2
m, C-4 H), 5.10 (1H, brs, C-1 H), 7.35 (1H, t, J¼7.0 Hz,
5
3
00 00 00
OCO(CH ) (CH ) CH ), 1.62 (2H, brs, OCOCH CH
2
C-4 H), 7.47 (2H, t, J¼7.4 Hz, C-3 H and C-5 H), 7.87
2
2
2 3
3
2
00
(
3
CH ) CH ), 2.35 (2H, t, J¼7.3 Hz, OCOCH (CH ) CH ),
(1H, s, C-5H) and 8.02 (2H, d, J¼7.6 Hz, C-2 H and
00
C-6 H); C NMR (75.5 MHz, CDCl ): d 11.37 (OCOCH -
3 2
2
3
3
2
2 4
3
13
.20 (2H, brs, 2£OH), 3.45 (1H, brs, OH), 3.93 (1H, d,
0
0
0
CH ), 29.83 (OCOCH CH ), 68.41 (C-4 ), 71.36 and 71.62
3 2 3
J¼6.6 Hz, C-2 H), 4.03 (1H, brs, C-3 H), 4.35 (1H, d,
0
1H, brs, C-1 H), 7.31–7.36 (1H, m, C-4 H), 7.43–7.48
0
0 0 0 00 00
(C-3 and C-1 ), 75.37 (C-2 ), 121.22 (C-3 and C-5 ),
130.10 (C-4 ), 131.70 (C-2 and C-6 ), 136.47 (C-5), 142.00
J¼11.5 Hz, C-4 H ), 4.44 (1H, d, J¼11.8 Hz, C-4 H ), 5.26
a
b
0
2H, m, C-3 H and C-5 H), 7.87 (1H, s, C-5H) and 8.0 (2H,
00
00
00
00
(
(
0
0
00
00
(C-1 ), 152.30 (C-4) and 177.34 (CvO); IR (KBr): 3465
(OH), 3376 (OH), 3295 (OH), 2938, 1710 (CvO), 1211,
0
0
00
13
d, J¼7.8 Hz, C-2 H and C-6 H); C NMR (75.5 MHz,
2
1
CDCl ): d 13.22 (OCO(CH ) CH ), 21.69 (OCO(CH ) -
3
1053, 1014 and 755 cm ; FAB-HRMS: m/z 344.1242
þ
3
2 5
2 4
CH CH ), 24.12 (OCO(CH ) CH CH CH ), 28.02
2
([MþNa] , C H N O Na calcd 344.1222).
3
2 3
2
2
3
15 19 3 5
(
CH ), 33.45 (OCOCH (CH ) CH ), 65.36 and 65.62 (C-2
OCO(CH ) CH (CH ) CH ), 30.65 (OCOCH CH (CH ) -
2 2 2 2 2 3 2 2 2 3
0
and C-4 ), 69.97 (C-3 ), 72.26 (C-1 ), 118.10 (C-3 and
0
0
0
0
4.2.25. 2-Phenyl-4-(D-lyxo-4 -butanoyloxy-1 ,2 ,3 -tri-
hydroxybutyl)-2H-1,2,3-triazole (8c). It was obtained as
a white solid (318 mg) in 95% yield, mp 97–1008C. R : 0.52
3
2
2 4
3
0
0
0
00
C-5 ), 126.93 (C-4 ), 128.56 (C-2 and C-6 ), 133.59 (C-5),
0
38.86 (C-1 ), 149.38 (C-4) and 174.16 (CvO); IR (KBr):
0
00
00
00
f
0
0
444 (OH), 2954, 2925, 1722 (CvO), 1396, 1241, 1183,
22
1
3
1
(chloroform–methanol, 9:1); [a] ¼213.0 (c 0.01,
D
1
MeOH); H NMR (300 MHz, CDCl ): d 0.93 (3H, brs,
3
2
1
042 and 751 cm
þ
;
FAB-HRMS: m/z 400.1871
OCO (CH ) CH ), 1.65 (2H, brs, OCOCH CH CH ), 2.31
2
2
3
2
2
3
(
[MþNa] , C H N O Na calcd 400.1848).
(2H, brs, OCOCH CH CH ), 3.17 (3H, 3 brs, 1H each,
2 2 3
1
9
27
3
5
0
0
(2H, brs, C-4 H), 5.11 (1H, brs, C-1 H), 7.35 (1H, brs,
3
£OH), 3.93 (1H, brs, C-2 H), 4.16 (1H, brs, C-3 H), 4.27
0
hydroxybutyl)-2H-1,2,3-triazole (7g). It was obtained as
0
0
0
0
0
4
.2.22. 2-Phenyl-4-(D-arabino-4 -benzoyloxy-1 ,2 ,3 -tri-
00 00 00
C-4 H), 7.45 (2H, brs, C-3 H and C-5 H), 7.87 (1H, s,
0
(75.5 MHz, CDCl ): d 13.47 (OCO(CH ) CH ), 18.23
0
00
13
a white crystalline solid (55 mg) in 15% yield, mp 151–
3
C-5H) and 8.01 (2H, brs, C-2 H and C-6 H); C NMR
0
1
(
4
(
528C. R : 0.56 (chloroform–methanol, 9:1); [a] ¼214.8
f
D
3
2 2
3
1
c 0.01, MeOH); H NMR (300 MHz, DMSO-d ): d 3.68,
6
(OCOCH CH CH ), 35.91 (OCOCH CH CH ), 65.78
2 2 3 2 2 3
0
0 0 0 0
(C-4 ), 68.87 and 69.12 (C-3 and C-1 ), 72.87 (C-2 ),
.00 and 4.29 (3H, 3 brs, 3£OH), 4.54 (1H, m, C-2 H), 4.92
0
.38 (1H, brs, C-1 H), and 7.37–7.62 and 7.97–8.06 (11H,
0
00 00 00 00
118.73 (C-3 and C-5 ), 127.59 (C-4 ), 129.20 (C-2 and
C-6 ), 133.97 (C-5), 139.51 (C-1 ), 149.81 (C-4) and 174.05
1H, d, J¼7.0 Hz, C-3 H), 5.18–5.24 (2H, m, C-4 H), 5.36–
0
m, Ar-H and C-5H); C NMR (75.5 MHz, DMSO-d ): d
00
00
5
1
3
(CvO); IR (KBr): 3430 (OH), 3376 (OH), 3291 (OH),
21
6
0
0
0
0
6
1
1
6.29 and 68.19 (C-2 and C-4 ), 69.31 (C-3 ), 74.83 (C-1 ),
19.07, 128.12, 129.41, 130.28, 130.44, 133.91, 136.20,
40.39, 153.80 (aromatic carbons, C-4 and C-5) and 166.90
2932, 2363, 1692 (CvO), 1274, 1053, 1016 and 755 cm
þ
calcd 358.1379).
;
FAB-HRMS: m/z 358.1362 ([MþNa] , C H N O Na
1
6
21 3 5
(
1
CvO); IR (KBr): 3448 (OH), 2925, 1714 (CvO), 1279,
1
2
0
0
0
0
042 and 707 cm
þ
;
FAB-HRMS: m/z 392.1255
4.2.26. 2-Phenyl-4-(D-lyxo-4 -pentanoyloxy-1 ,2 ,3 -tri-
hydroxybutyl)-2H-1,2,3-triazole (8d). It was obtained as
a white solid (307 mg) in 88% yield, mp 65–678C. R : 0.53
(
[MþNa] , C H N O Na calcd 392.1222).
1
9 19 3 5
f
0
butyl)-2H-1,2,3-triazole (8a). It was obtained as a white
0
0
0
22
4
.2.23. 2-Phenyl-4-(D-lyxo-4 -acetoxy-1 ,2 ,3 -trihydroxy-
(chloroform–methanol, 9:1); [a] ¼29.9 (c 0.01, MeOH);
D
1
H NMR (300 MHz, CDCl ): d 0.89 (3H, t, J¼7.2 Hz,
3
crystalline solid (92 mg) in 30% yield, mp 130–1348C. R :
f
0
MeOH); H NMR (300 MHz, DMSO-d ): d 2.07 (3H, s,
OCO(CH ) CH ), 1.25–1.39 (2H, m, OCO(CH ) CH -
2 3
3
2 2
2
2
2
.49 (chloroform–methanol, 9:1); [a] ¼215.1 (c 0.01,
CH ), 1.54–1.64 (2H, m, OCOCH CH CH CH ), 2.33
3 2 2 2 3
D
1
(2H, t, J¼7.6 Hz, OCOCH (CH ) CH ), 3.05, 3.11 and 3.31
6
2
2 2
3
0
0
(1H, brs, C-3 H), 4.21–4.33 (2H, m, C-4 H), 5.10 (1H, brs,
OCOCH ), 3.70 (1H, t, J¼7.8 Hz, C-3 H), 4.05–4.11 (3H,
(3H, 3 brs, 1H each, 3£OH), 3.93 (1H, brs, C-2 H), 4.15
3
0
0
0
brs, 3£OH), 4.67 (1H, d, J¼7.5 Hz, C-2 H), 4.81–4.86 (2H,
0
0
0
00
m, C-4 H), 5.61 (1H, d, J¼5.54 Hz, C-1 H), 7.44 (1H, t,
C-1 H), 7.35 (1H, t, J¼7.3 Hz, C-4 H), 7.47 (2H, t,
0
0
00
00
and 8.02–8.05 (3H, m, C-2 H, C-6 H and C-5H); C NMR
00 00
J¼7.2 Hz, C-4 H), 7.57–7.63 (2H, m, C-3 H and C-5 H)
J¼7.5 Hz, C-3 H and C-5 H), 7.87 (1H, s, C-5H) and
00
00
13
00 00
(75.5 MHz, CDCl ): d 14.40 (OCO(CH ) CH ), 22.97
13
8.02 (2H, d, J¼8.0 Hz, C-2 H and C-6 H); C NMR
(
6
(
75.5 MHz, DMSO-d ): d 21.81 (OCOCH ), 66.43 and
6 3
3
2 3
3
0
0
0
0
C-3 and C-5 ), 128.29 (C-4 ), 130.66 (C-2 and C-6 ),
6.67 (C-4 and C-3 ), 68.07 (C-2 ), 73.67 (C-1 ), 119.11
(OCO (CH ) CH CH ), 27.68 (OCOCH CH CH CH ),
2
2
2
3
2
2
2
3
0
0
00
00
00
00
35.98 (C-5), 140.38 (C-1 ), 153.72 (C-4) and 171.37
0
70.04 (C-3 and C-1 ), 73.73 (C-2 ), 119.60 (C-3 and
34.64 (OCOCH (CH ) CH ), 66.72 (C-4 ), 69.78 and
2
2 2
0
3
00
0
0
C-5 ), 128.48 (C-4 ), 130.09 (C-2 and C-6 ), 134.85 (C-5),
00
1
0
140.38 (C-1 ), 150.67 (C-4) and 175.13 (CvO); IR (KBr):
0
00
00
00
(
2
CvO); IR (KBr): 3446 (OH), 3367 (OH), 3271 (OH),
2
1
00
3374 (OH), 3377 (OH), 3282 (OH), 2932, 1691 (CvO),
938, 1707 (CvO), 1269, 1053, 1014 and 758 cm ; FAB-
þ
HRMS: m/z 330.1076 ([MþNa] , C H N O Na calcd
1
4
17
3
5
2
1
3
30.1066).
1278, 1052, 1015, 757 and 667 cm ; FAB-HRMS: m/z
þ
3
72.1559 ([MþNa] , C H N O Na calcd 372.1535).
1
7
23
3
5
0
hydroxybutyl)-2H-1,2,3-triazole (8b). It was obtained as
0
0
0
4
.2.24. 2-Phenyl-4-(D-lyxo-4 -propanoyloxy-1 ,2 ,3 -tri-
0
0
0
0
4.2.27. 2-Phenyl-4-(D-lyxo-4 -hexanoyloxy-1 ,2 ,3 -tri-
hydroxybutyl)-2H-1,2,3-triazole (8e). It was obtained as
a white crystalline solid (112 mg) in 35% yield, mp 110–

A. Bhattacharya et al. / Tetrahedron 59 (2003) 10269–10277
10277
a white solid (308.5 mg) in 85% yield, mp 102–1048C. R :
f
140.18, 150.45 (aromatic carbons, C-4 and C-5) and 167.59
(CvO); IR (KBr): 3463 (OH), 3375 (OH), 3307 (OH),
2
2
0
MeOH); H NMR (300 MHz, CDCl ): d 0.87 (3H, t,
.55 (chloroform–methanol, 9:1); [a] ¼212.0 (c 0.01,
D
1
21
2939, 1690 (CvO), 1283, 1053, 1012 and 706 cm ; FAB-
þ
392.1222).
3
J¼6.6 Hz, OCO(CH ) CH ), 1.28–1.30 (4H, m,
HRMS: m/z 392.1245 ([MþNa] , C H N O Na calcd
19 19 3 5
2
4
3
OCO(CH ) (CH ) CH ), 1.58–1.66 (2H, m, OCOCH -
2
2
2 2
3
2
CH (CH ) CH ), 2.32 (2H, t, J¼7.4 Hz, OCOCH (CH ) -
2
2 2
3
2
2 3
CH ), 3.12, 3.17 and 3.41 (3H, 3 brs, 1H each, 3£OH), 3.93
3
0
0
(
1H, brs, C-2 H), 4.15 (1H, brs, C-3 H), 4.21–4.33 (2H, m,
0
0
C-4 H), 5.10 (1H, brs, C-1 H), 7.35 (1H, t, J¼7.2 Hz,
Acknowledgements
0
0
00
00
C-4 H), 7.47 (2H, t, J¼7.5 Hz, C-3 H and C-5 H), 7.87
00
(
C-6 H);
1H, s, C-5H) and 8.01 (2H, d, J¼7.7 Hz, C-2 H and
We thank the Danish International Development Agency
(DANIDA, Denmark) and the Council of Scientific and
Industrial Research (CSIR, India) for financial assistance.
00
13
C
OCO(CH ) CH ), 23.01 (OCO (CH ) CH CH ), 25.30
NMR (75.5 MHz, CDCl ):
d
14.61
3
(
(
2
4
3
2 3
2
3
OCO(CH ) CH CH CH ), 32.01 (OCOCH CH (CH ) -
2
2
2
2
3
2
2
2 2
0
CH ), 34.89 (OCOCH (CH ) CH ), 66.69 (C-4 ), 69.73
2 3
3
2
3
0
C-5 ), 128.48 (C-4 ), 130.09 (C-2 and C-6 ), 134.86 (C-5),
0
0
00
and 70.00 (C-3 and C-1 ), 73.75 (C-2 ), 119.60 (C-3 and
00
00
00
00
40.37 (C-1 ), 150.69 (C-4) and 175.15 (CvO); IR (KBr):
References
0
0
1
3
1
3
463 (OH), 3378 (OH), 3298 (OH), 2936, 1709 (CvO),
2
1. Zaks, A.; Dodds, D. R. Drug Discov. Today 1997, 2, 513–531.
2. Parmar, V. S.; Prasad, A. K.; Pati, H. N.; Kumar, R.; Azim, A.;
Roy, S.; Errington, W. Bioorg. Chem. 1999, 27, 119–134.
1
498, 1193, 1053, 1015 and 757 cm ; FAB-HRMS: m/z
þ
86.1693 ([MþNa] , C H N O Na calcd 386.1692).
1
8
25
3
5
3
. Bashir, N. B.; Phythian, S. J.; Reason, A. J.; Roberts, S. M.
J. Chem. Soc., Perkin Trans. 1 1995, 2203–2222.
0
0
0
0
hydroxybutyl)-2H-1,2,3-triazole (8f). It was obtained as
4
.2.28. 2-Phenyl-4-(D-lyxo-4 -heptanoyloxy-1 ,2 ,3 -tri-
4. Collins, P.; Ferrier, R. Monosaccharides: Their Chemistry and
Their Roles in Natural Products; Wiley: UK, 1995; 431.
5. Sekiyama, T.; Hatsuya, S.; Tanaka, Y.; Uchiyama, M.; Ono,
N.; Iwayama, S.; Oikawa, M.; Suzuki, K.; Okunishi, M.; Tsuji,
T. J. Med. Chem. 1998, 41, 1284–1298.
a white solid (335.5 mg) in 89% yield, mp 97–988C. R :
f
0.57 (chloroform–methanol, 9:1); [a] ¼217.8 (c 0.01,
MeOH); H NMR (300 MHz, CDCl ): d 0.86 (3H, t,
2
2
D
1
3
J¼6.8 Hz, OCO(CH2)5 CH3), 1.26–1.29 (6H, brs,
OCO(CH ) (CH ) CH ), 1.55–1.62 (2H, m, OCOCH -
2
6. Wengel, J. Acc. Chem. Res. 1999, 32, 301–310.
7. Zhang, X.; Qing, F.-L. J. Org. Chem. 2002, 67, 1016–1019.
8. Yamada, K.; Sakata, S.; Yoshimura, Y. J. Org. Chem. 1998,
63, 6891–6899.
2
2
2 3
3
CH (CH ) CH ), 2.32 (2H, t, J¼7.5 Hz, OCOCH (CH ) -
2
2 3
3
2
2 4
0
CH ), 2.36 (3H, brs, 3£OH), 3.92 (1H, d, J¼4.6 Hz, C-2 H),
3
0
0
4
5
.16 (1H, d, J¼4.8 Hz, C-3 H), 4.21–4.33 (2H, m, C-4 H),
0
.11 (1H, d, J¼5.9 Hz, C-1 H), 7.35 (1H, t, J¼7.3 Hz,
9. Reist, E. J.; Fisher, L. V.; Goodman, L. J. Org. Chem. 1968,
33, 189–192.
00
00
00
C-4 H), 7.47 (2H, t, J¼7.98 Hz, C-3 H and C-5 H), 7.87
00
(
C-6 H);
1H, s, C-5H) and 8.01 (2H, d, J¼7.8 Hz, C-2 H and
10. Prasad, A. K.; Wengel, J. Nucleosides Nucleotides 1996, 15,
1347–1359.
0
0
13
C
NMR (75.5 MHz, CDCl ):
d
OCO(CH ) CH ), 22.31 (OCO(CH ) CH CH ), 24.70
13.84
3
(
(
11. Prasad, A. K.; Sorensen, M. D.; Parmar, V. S.; Wengel, J.
Tetrahedron Lett. 1995, 36, 6163–6166.
2
5
3
2 4
2
3
OCO(CH ) CH CH CH ), 28.63 (OCO(CH ) CH CH -
2
2
3
2
2
3
2 2
2
CH CH ), 31.26 (OCOCH CH (CH ) CH ), 34.05
3
12. Sharma, S. K.; Roy, S.; Kumar, R.; Parmar, V. S. Tetrahedron
Lett. 1999, 40, 9145–9146.
2
3
2
2
2 3
0
C-3 and C-1 ), 72.87 (C-2 ), 118.72 (C-3 and C-5 ),
(
OCOCH (CH ) CH ), 65.79 (C-4 ), 68.83 and 69.11
2
2 4
3
0
0
0
00
27.59 (C-4 ), 129.20 (C-2 and C-6 ), 133.98 (C-5), 139.50
00
(
13. Prasad, A. K.; Himanshu; Bhattacharya, A.; Olsen, C. E.;
Parmar, V. S. Bioorg. Med. Chem. 2002, 10, 947–951.
14. Prasad, A. K.; Roy, S.; Kumar, R.; Kalra, N.; Wengel, J.;
Olsen, C. E.; Cholli, A. L.; Samuelson, L. A.; Kumar, J.;
Watterson, A. C.; Gross, R. A.; Parmar, V. S. Tetrahedron
2003, 59, 1333–1338.
0
C-1 ), 149.81 (C-4) and 174.27 (CvO); IR (KBr): 3421
0
00
00
1
(
00
(
1
(
OH), 3367 (OH), 3278 (OH), 2949, 1691 (CvO), 1280,
2
1
052, 1015 and 758 cm ; FAB-HRMS: m/z 400.1848
þ
[MþNa] , C H N O Na calcd 400.1848).
1
9 27 3 5
1
5. Raunak; Prasad, A. K.; Shakil, N. A.; Himanshu; Parmar, V. S.
Pure Appl. Chem. 2001, 73, 167–174.
0
0
0
0
4.2.29. 2-Phenyl-4-(D-lyxo-4 -benzoyloxy-1 ,2 ,3 -tri-
hydroxybutyl)-2H-1,2,3-triazole (8g). It was obtained as
16. Himanshu; Tyagi, R.; Olsen, C. E.; Errington, W.; Parmar,
V. S.; Prasad, A. K. Bioorg. Med. Chem. 2002, 10, 963–968.
17. Tipson, R. S. Methods in Carbohydrates Chemistry; Aca-
demic: New York, 1963; Vol. 2. p 16.
a white crystalline solid (118 mg) in 32% yield, mp 137–
2
2
1
(
408C. R : 0.57 (chloroform–methanol, 9:1); [a] ¼229.9
f
D
1
c 0.01, MeOH); H NMR (300 MHz, CDCl ): d 3.23 (3H,
3
0
0
0
brs, 3£OH), 4.06 (1H, brs, C-2 H), 4.33 (1H, brs, C-3 H),
18. Hann, R. M.; Hudson, C. S. J. Am. Chem. Soc. 1944, 66,
735–738.
0
4
7
(
(
.49–4.60 (2H, m, C-4 H), 5.17 (1H, d, J¼5.75 Hz, C-1 H),
.36–7.50 (6H, m, Ar-H), 7.90 (1H, s, C-5H) and 8.01–8.05
19. Haskins, W. T.; Hann, R. M.; Hudson, C. S. J. Am. Chem. Soc.
1946, 68, 1766–1769.
1
3
4H, m, Ar-H); C NMR (75.5 MHz, CDCl ): d 67.02
3
C-4 ), 69.65 and 69.90 (C-3 and C-1 ), 73.53 (C-2 ),
19.39, 128.23, 129.00, 129.85, 130.30, 133.86, 134.64,
0
0
0
0
20. Haskins, W. T.; Hann, R. M.; Hudson, C. S. J. Am. Chem. Soc.
1945, 67, 939–941.
1