Synthesis of glycoconjugate benzothiazoles via cleavage of benzotriazole ring

Article abstract of DOI:10.1021/jo3021049

A concise and efficacious benzotriazole-mediated novel two-step protocol has been developed for easy access to glycoconjugate benzothiazoles from protected carbohydrates. The benzotriazolemethanethione 3, prepared by the reaction of free alcohol with bis(1H-benzo[1,2,3]triazol-1-yl)methanethione, on treatment with silanes or stannane under heating or microwave irradiation undergoes free radical β-scission of N-N bond and affords diverse range of 2-O-substituted benzothiazoles 4 via cyclative elimination of molecular nitrogen. The structures of all of the compounds have been elucidated using IR, NMR, MS, and elemental analysis, and five of them have been characterized by single-crystal X-ray analysis.

Full text of DOI:10.1021/jo3021049

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Article
Synthesis of Glycoconjugate Benzothiazoles
via Cleavage of Benzotriazole Ring
Dhananjay Kumar, Amrita Mishra, Bhuwan B Mishra, Subrato Bhattacharya, and Vinod K. Tiwari
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo3021049 • Publication Date (Web): 27 Dec 2012
Downloaded from http://pubs.acs.org on December 30, 2012
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Synthesis of Glycoconjugate Benzothiazoles via Cleavage of Benzotriazole
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Ring
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Dhananjay Kumar, Amrita Mishra, Bhuwan B. Mishra, Subrato Bhattacharya, Vinod K. Tiwari*
Department of Chemistry, Centre of Advanced Study, Banaras Hindu University, Varanasiꢀ
221005, India
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*Corresponding author: Eꢀmail: tiwari_chem@yahoo.co.in, Tel.: +91ꢀ542ꢀ6702466; fax: +91ꢀ
542ꢀ236817
Abstract: A concise and efficacious benzotriazole mediated novel twoꢀstep protocol has been
developed for an easy access to glycoconjugate benzothiazoles from protected carbohydrates.
The benzotriazolemethanethione 3, prepared by the reaction of free alcohol with bis(1Hꢀ
benzo[1,2,3]triazolꢀ1ꢀyl)methanethione, on treatment with silanes or stannane under heating or
microwave irradiation undergoes free radical βꢀscission of NꢀN bond and affords diverse range
of 2ꢀOꢀsubstituted benzothiazoles 4 via cyclativeꢀelimination of molecular nitrogen. Structure
of all the compounds has been elucidated using IR, NMR, MS and elemental analysis, where
five of them have been characterized by single crystal Xꢀray analysis.
Keywords: benzotriazole, cyclization, elimination, glycoconjugate, benzothiazoles, heterocycle
Manuscript dedicated to Prof. Alan R. Katritzky, Director, Centre for Heterocyclic Compounds,
University of Florida, Gainesville, FL, USA
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INTRODUCTION
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Benzotriazole methodology, a versatile, useful, and one of the most successful synthetic
protocol investigated so far, has now grown from an obscure level to very high popularity.1,2
Despite the high stability of benzotriazole in synthetic transformations3 there are few reactions
reported to involve the disruption of the benzotriazole ring i.e. in the synthesis of indoles,
benzoazines, quinazolines, 3,4ꢀdihydroquinazolines, and quinazolineꢀ4ꢀthiones.4 Such ring
opening of benzotriazole derivatives provide an attractive way to generate a wide variety of
benzoheterocycles.1f,2 Thus, we envisioned exploring the feasibility of utilizing benzotriazole
methodology for construction of benzothiazole ring on protected sugars to afford
glycoconjugate benzothiazoles in an elegant and efficient way.
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Benzothiazole is a privileged bicyclic ring system in myriad compounds of value to
medicine and agriculture.5ꢀ7 The benzothiazoleꢀconjugation would be effectively utilized for
improving the inhibition of carbohydrateꢀbased glycosidase inhibitors and enhance the
interaction of carbohydrateꢀbased ligands to carbohydrateꢀbinding proteins. However, reports
on 2ꢀOꢀsubstitued benzothiazoles are highly scarce and pose significant challenges for their
sustainable development. The customary methods to access benzothiazoles involve the
condensation of oꢀaminothiophenols with substituted nitriles, aldehydes, acyl chlorides,
carboxylic acids, or esters8 but difficulty in the synthesis of readily oxidizable oꢀ
aminothiophenols, restricts their pervasive applications. Oxidative cyclization of
thiobenzanilides using various oxidants, including Jacobson’s and Hugershoff’s methods, are
other routes to access benzothiazoles.9 However, low functional group tolerance limits the
utility of these approaches. Other methods include, the reaction of oꢀaminothiophenol with
dibenzyl disulfides and βꢀchlorocinnamaldehydes, reaction of Sꢀaryl thiobenzoate with
arylhaloamines, from 1,2,3ꢀbenzodithiazoleꢀ2ꢀoxides, radical cyclization of benzyne
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intermediates, reduction of o,o′ꢀdinitrodiphenyl disulfide and Grignard reactions of
arylisothiocyanates.10ꢀ13 Intramolecular cyclization of thioformanilides using hypervalent iodine
reagents and Pd/Cuꢀcatalyzed cyclization of 2ꢀhalophenylthiobenzamides also provide an easy
access to benzothiazoles.14 However, the preꢀfunctionalization of starting material and poor
performance in gram scale synthesis are among the major drawbacks of these approaches.
Over recent years, there is an increasing demand for new carbohydrate scaffolds for the
numerous biological, medicinal and pharmacological investigations.15 As part of our ongoing
work on development of new benzotriazole methodologies for the synthesis of heterocyclic and
carbohydrate based scaffolds of multifaceted biological profiles,16 we herein describe a novel
two step protocol for an easy access to diverse 2ꢀOꢀsubstitued glycoconjugate benzothiazoles 4
from carbohydrate based benzotriazolemethanethiones 3, readily prepared from protected sugars
1 using benzotriazole as a synthetic auxiliary (Scheme 1).
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S
N
N
S
N
Bt
Bt
Silanes/ Stannane
Aprotic solvents
Heating at 80oC, 5-6 h
O
2
S
O
Sugar
Sugar
OH
Pyridine (0.3 equiv)
Et3N (0.2 equiv)
DCM, 5-12h, RT
N
or MW, 5-15 min
1
4
3
yield = 92-98 %
yield = 75-90 %
Scheme 1. The reaction of protected sugars 1 with bis(1Hꢀbenzo[1,2,3]triazolꢀ1ꢀ
yl)methanethione 2
RESULTS AND DISCUSSION
We began our study by examining a model reaction of 1,2:3,4ꢀdiꢀOꢀisopropylideneꢀαꢀ
Dꢀ
galactopyranose 1a with bisꢀbenzotriazole methanethione 2 in presence of Et3N (0.2 equiv) and
pyridine (0.3 equiv) in dichloromethane at room temperature to afford 6ꢀOꢀ(1,2:3,4ꢀdiꢀOꢀ
isopropylidineꢀαꢀDꢀgalactopyranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀcarbothioate
3a
in
significant yield. The high stability of resulting adduct 3a prevented it to be further attacked by
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another sugar molecule, and indeed no bisubstituted products were observed during synthesis of
carbohydrate based benzotriazolemethanethiones 3aꢀk (Table 1) via reaction of protected sugars
1aꢀk and compound 2. Using extensive spectral studies (IR, 1H, and 13C NMR), the structures of
compounds 3aꢀk were elucidated. A single crystal Xꢀray analysis17 evidenced the unambiguous
structure of compound 3a (see the Supporting Information, Figure S1).
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Table 1. Synthesis of carbohydrate based benzotriazolemethanethiones 3aꢀk
entrya substrate
productb
time (h)c
yield (%)d
1
5
90
O
O
O
O
S
2
3
6
6
89
87
O
O
N
3b
N
N
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86
87
78
BnO
O
O
O
O
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N
S
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aMolar ratios: protected sugar, Et3N, bisꢀbenzotriazole methanethiones. Carbohydrate based
b
c
d
benzotriazolemethanethiones. Reaction time. Yield reported after purification by column
chromatography.
However, reaction of 3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylideneꢀαꢀ ꢀxyloꢀhexofuranosꢀ5ꢀulose 5
D
with compound 2 to access corresponding carbohydrate based benzotriazolemethanethione 3
under our standardized reaction condition was not successful, rather a mixture of two
regioisomers,
5ꢀ(1′Hꢀbenzo[1,2,3]triazolꢀ1′ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀdiꢀOꢀisopropylideneꢀ5,6ꢀOꢀ
ꢀglucofuranose 6 and 5ꢀ(2Hꢀbenzo[1,2,3]triazolꢀ2ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀdiꢀOꢀ
thiocarbonateꢀαꢀ
D
isopropylideneꢀ5,6ꢀOꢀthiocarbonateꢀαꢀ
D
ꢀglucofuranose 7 were obtained in a ratio of 73:27%,
respectively (Scheme 2).
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Scheme 2. Reaction of 3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylideneꢀαꢀ
compound 2
D
ꢀxyloꢀhexofuranosꢀ5ꢀulose 5 with
A plausible mechanism involves the initial nucleophilic attack by hydroxyl group of
hydroxy ketone 5 on thiocarbonyl carbon of compound 3 to afford a carbohydrate based
benzotriazolemethanethione intermediate I that readily passes to a transition state (TS) via
nucleophilic attack of benzotriazole moiety through N1 or N2 and subsequent nucleophilic
addition of carbonyl oxygen on thiocarbonyl carbon as outlined in Scheme 3. The benzotriazole
moiety by virtue of πꢀπ interaction with phenyl ring facilitates a preferred Siꢀface attack and
results in an observed stereochemistry of products, also confirmed by single crystal Xꢀray
analysis (Figure 1). The structures of compounds 6 & 7 were elucidated using extensive spectral
1
studies (IR, H, and 13C NMR) and single crystal Xꢀray analysis (see the Supporting
Information, Figure S2 and S3).
Scheme 3. The plausible mechanism for the formation of regioisomers 6 & 7
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Figure 1. Offset πꢀπ stacking interactions in regioisomers 6 & 7
Treatment of compound 3a with reagents capable of inducing free radical mechanism
furnished 6ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ1,2:3,4ꢀdiꢀOꢀisopropylidineꢀαꢀ
ꢀgalactopyranose 4a in good
D
to excellent yield. We briefly studied the effect of various reagents (e.g. silanes and stannane) in
terms of yield and reaction time. The cyclization of 3a using Bu3SnH at 80 °C in toluene
furnished 4a quantitatively in 5 h. Encouraged by this result, we further examined this reaction
in the presence of AIBN (5 mol%) as radical initiator and obtained high yield of product 4a in
significantly reduced reaction time (entry 11, Table 2). Although, simple, low molecular weight
silanes would be very acceptable alternatives, however greater strength of the SiꢀH (377 kJ molꢀ
1) in Et3SiH compared with SnꢀH bond (310 kJ molꢀ1) in nꢀBu3SnH, such cyclizations are
observed comparatively slow and require considerably high temperature or added initiators.18a
In our investigation, the cyclizations with Et3SiH and Pri3SiH resulted in poor yields of
products, unless 5 mol% of AIBN was used as initiator. However, the reactions carried out in
presence of silanes having radical stabilizing groups i.e. phenylꢀsubstituent in MePh2SiH,
ButPh2SiH and Ph3SiH afforded moderate yield of products in 5ꢀ6 h, even without using radical
initiator, which suggested that the bondꢀweakening effects operative on phenyl substitution.18b
The uniformity of SiꢀH bond strengths between Et3SiH and Pri3SiH gives almost the similar
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results. However, results obtained with phenylꢀsubstituted silanes are quite noticeable,
particularly due to the radical stabilization by πꢀconjugation of phenyl group(s) that weakens the
SiꢀH bond. Further, using AIBN as initiator for cyclization dramatically accelerated the reaction
and furnished product in a quantitative yield with significant reduction of reaction time (Table
2). Bu3SnH proved to be best among an array of reagent tested and addition of AIBN was
crucial for aforementioned conversion (entry 11, Table 2). In the reaction optimization study
executed by varying the ratio of Bu3SnH under refluxing condition, an increase in total yield of
4a was observed while increasing the reagent quantitatively. The yield of compound 4a was
optimum using two equivalents of Bu3SnH at 80 °C. In addition, we investigated the reaction
under microwave (MW) condition, where significant reduction in reaction time ranging from 5ꢀ
15 min was observed (Table 2).
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Table 2. Optimization of radical conversion to 4a using 2 molar equivalents of reagents
entry
reagent
initiatora
temp (°C)b
yield %
(time)c
40(4)
0(6)
yield %
(time)d
70(15)
0(15)
(Mol%)
1
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Et3SiH
5
0
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0
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0
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0
80
150
80
Et3SiH
Pri3SiH
Pri3SiH
45(4)
5(6)
75(15)
18(15)
89(15)
63(15)
96(15)
65(15)
150
80
MePh2SiH
MePh2SiH
ButPh2SiH
ButPh2SiH
60(4)
49(6)
89(4)
50(5)
150
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150
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90(3)
60(5)
98(1)
92(5)
98(10)
74(10)
98(5)
Ph3SiH
Ph3SiH
Bu3SnH
Bu3SnH
10
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12
80
97(10)
aAIBN (azobisisobutyronitrile) was used as radical initiator. Reaction temperature 80ꢀ150 °C.
b
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d
cReaction time in hours under heating condition, Reaction time in minutes under microwave
condition.
The solvent effect was briefly investigated using various solvents in the presence of AIBN (5
mol %) and Bu3SnH (2 molar equiv) at 80 °C (Table 3). The results illustrated the poor
performance of cyclohexane, nꢀhexane, benzene, 1,4ꢀdioxane, dichloromethane and chloroform
in terms of yield and reaction time. Using toluene as a solvent, the reaction accomplished in
significantly less time with much higher yield of product, which suggested the toluene as
solvent of choice for cyclization to product 4a.
Table 3. Solvent optimization for conversion from 3a to 4a using Bu3SnH (2 molar equiv) in
presence of AIBN (5 mol %)
entry
solventa
cyclohexane
nꢀhexane
time (h)b
yield (%)c
1
2
3
4
5
6
7
6
5
75
75d
85
benzene
5
toluene
1
98
1,4ꢀdioxane
dichloromethane
chloroform
8
80
12
12
60d
62d
a2.0 mL of solvent was used for 1 mmol of 3a. bReaction time 1ꢀ
12 h. cIsolated yield 60ꢀ98%. dReaction in sealed tube.
The extensive spectral studies (IR, 1H, 13C NMR and MS) evidenced the unambiguous structure
1
of compound 4a. Like H NMR spectra of compound 3a having four separate resonances (one
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proton each) for the characteristic benzotriazolyl CꢀH protons, the compound 4a also exhibited
four proton resonances in aromatic region with a different splitting pattern, thus ruled out the
formation of possible deoxy product19 under our standardized conditions. Also, the mass
spectrum of 4a exhibited [M+H]+ peak at m/z 394, which was 28 units less than the molecular
ion peak [M+H]+ of 3a observed at m/z 422. Therefore, the compound 4a might have been
formed by the loss of molecular nitrogen (N2) from 3a, also evidenced by their respective single
crystal Xꢀray analysis (see the Supporting Information, Figure S1 and S4).
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Thus, under optimized reaction conditions, all the developed carbohydrate based
benzotriazolemethanethione 3aꢀk were cyclized to their respective glycoconjugate
benzothiazoles 4aꢀk in excellent yields ranging from 92ꢀ98% (Table 4). The structure of
compounds 4aꢀk were deduced from their extensive spectral studies (IR, NMR and MS), and
single crystal Xꢀray analysis.
Table 4. Synthesis of glycoconjugate benzothiazoles 4aꢀk
entry substratea
product
yield % (time)b
yield % (time)c
1
2
98(1)
98(5)
3a
3b
95(1)
97(5)
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96(1)
98(5)
97(6)
3c
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94(1)
3d
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95(1)
97(1)
97(5)
98(6)
3e
3f
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95(1)
96(1)
97(5)
98(5)
3g
3h
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96(1)
98(7)
3i
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92(1)
94(1)
95(5)
96(6)
3j
3k
aMolar ratios: carbohydrate based benzotriazolemethanethiones 3aꢀk, Bu3SnH (1:2 equivalent),
b
c
and AIBN (5 mol%). Reaction time in hours under heating condition. Reaction time in
minutes under microwave condition.
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A part from highly functionalized carbohydrates, we next synthesized Oꢀcholesteryl
methanethione 9 by the reaction of cholesterol 8 with bis(1Hꢀbenzo[1,2,3]triazolꢀ1ꢀ
yl)methanethione 2, and successfully executed the synthesis of Oꢀcholesteryl benzothiazole 10
in quantitative yield via radical cyclization under our standardized conditions (Scheme 4). Thus,
the developed methodology is well tolerated to a number of functional groups such ethers,
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acetals, thioethers, esters, and alkenes. Extensive spectral studies (IR, H, and C NMR) and
single crystal Xꢀray analysis evidenced the formation of benzothiazole ring in the compound 10
(see the Supporting Information, Figure S5).
Scheme 4. Synthesis of Oꢀcholesteryl benzothiazole 10
Although a detailed understanding of the mechanism will require additional studies, we
assume that the transformation of carbohydrate based benzotriazolemethanethione 3 to
glycoconjugate benzothiazole 4 proceeds via free radical cyclization as outlined in Scheme 5.
The homolytic cleavage of tributylstannane initiates a radical reaction, which is propagated by
subsequent addition of stannanyl radical to sulfur of thiocarbonyl20 forming an intermediate A
that rapidly adds a hydrogen radical to furnish an intermediate B. The βꢀscission by the radical
cleavage of benzotriazole ring results in the formation of an intermediate C. Elimination of a
nitrogen molecule (N2) from biradical intermediate C affords a resonance stabilized aryl radical
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intermediate D that cyclizes to furnish benzothiazole 4 via a thermodynamically favorable and
thermally induced oxidation process leading to aromatization at the cost of 2σꢀbond to a resulted
πꢀbond in final product. The trialkylsilyl radicals also add rapidly to sulfur in thiocarbonyl
compounds, and possibly follow the same mechanistic pathway. However, addition of R3Si● is
likely to be much less readily reversible than the corresponding addition of Bu3Sn●, because the
SiꢀS bond is appreciably stronger than the SnꢀS bond.21 Therefore, this may reduce the rate of
decay for biradical intermediate C to furnish D that cyclizes to glycoconjugate benzothiazole 4.
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Scheme 5. The postulated mechanism for the formation of benzothiazoles
CONCLUSION
In conclusion, a concise and efficacious benzotriazole mediated novel twoꢀstep protocol for
an easy access to diverse glycoconjugate benzothiazoles from protected carbohydrates has been
developed. The short reaction period, simple workup, good yield, and mild conditions of this
methodology demonstrate significant compatibility towards acid and base sensitive
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functionalities. Unlike carbohydrate derivatives e.g. Oꢀ(Sꢀmethyldithiocarbonate)ꢀ, Oꢀ
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phenoxythiocarbonyl, phenyꢀ1ꢀthio,
Oꢀpentafluorophenylthionocarbonate, Oꢀthiocarbonyl
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imidazolide etc. utilized earlier for deoxygenation,19 the developed methodology described
herein does not give deoxy products even in trace amounts. In addition to the generality with
respect to the substrate scope, facile accessibility to the starting materials is also highly
appealing. The synthesis of benzothiazoles via benzotriazole ring cleavage has not been realized
so far, thus, this approach should be of further interest to synthetic and medicinal chemists. The
developed methodology performs well in small as well as gram scale synthesis of
benzothiazoles, thus may have industrial significance. The biological screening of all the
developed glycoconjugate benzothiazoles is under way.
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EXPERIMENTAL SECTION
General Remarks.
All the reactions were executed in anhydrous solvents under an argon atmosphere in one hour
oven dried glassware at 100 °C. All reagents and solvents were of pure analytical grade. Thin
layer chromatography (TLC) was performed on 60 F254 silica gel, preꢀcoated on aluminum plates
and revealed with either a UV lamp (λmax = 254 nm) or a specific colour reagent (Draggendorff
reagent or iodine vapours) or by spraying with methanolicꢀH2SO4 solution and subsequent
charring by heating at 100 °C. 1H and 13C NMR were recorded at 300 and 75 MHz, respectively.
Chemical shifts given in ppm downfield from internal TMS; J values in Hz. Mass spectra
recorded using electrospray ionization mass spectrometry (ESIꢀMS). Infrared spectra recorded as
Nujol mulls in KBr plates. Elemental analysis was performed using a C, H, N analyzer and
results were found to be within ± 0.4% of the calculated values. Reactions under microwave
were carried out in a singleꢀmode microwave reactor from CEM Discover® LabMate, Wattage:
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300 W, Tꢀ300°C. Singleꢀcrystal Xꢀray data collected on Xcalibur Eos (Oxford) CCDꢀ
diffractometer.
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Procedure for the synthesis of protected sugars (1aꢀk & 5). The compounds 1aꢀj & 5 were
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prepared from readily available carbohydrates (
using standard protection methodologies.22
D
ꢀglucose,
D
ꢀgalactose,
D
ꢀribose and ꢀxylose)
D
3ꢀOꢀBenzylꢀ5ꢀbenzylthioꢀ5,6ꢀdideoxyꢀ1,2ꢀOꢀisoproyledeneꢀαꢀ
D
ꢀxyloꢀheptofuranuronose
ꢀxyloꢀ
(1k). Ethyl 3ꢀOꢀbenzylꢀ5ꢀbenzylthioꢀ5,6ꢀdideoxyꢀ1,2ꢀOꢀisoproyledeneꢀαꢀ
D
heptofuranuronoate23a (1.56 g, 3.30 mmol), prepared by the 1,4ꢀconjugate addition of benzyl
mercapton to ethyl (3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylideneꢀ1,4ꢀpentofuranoseꢀ4ꢀyl)ꢀheptꢀ5ꢀenoate,23b
was taken in anhydrous THF and added dropꢀwise to the stirring slurry of LiAlH4 (250 mg, 6.60
mmol) in anhydrous THF at 0°C under a nitrogen atmosphere. The reaction mixture was stirred
for 30 min at 0°C followed by further stirring at ambient temperature for 3h. On completion
(monitored by TLC), the reaction was quenched by adding saturated aqueous Na2SO4 solution
and filtered. The solid cake was washed with THF, and the filtrate was concentrated under
reduced pressure followed by extraction with chloroform (2 x100mL). The organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced pressure. Further purification
using flash column chromatography using gradient mixtures of ethylacetate and nꢀhexane
afforded pure compound 1k (1.35 g, yield 95%) as viscous liquid. Rf = 0.5 (40% ethyl acetate/nꢀ
hexane); 1H NMR (300 MHz, CDCl3): δ 7.33ꢀ7.21 (m, 10H), 5.89 (d, J = 3.6 Hz, 1H), 4.67 (d, J
= 11.0 Hz, 1H), 4.56 (d, J = 4.2 Hz, 1H), 4.55 (d, J = 11.0 Hz, 1H), 4.10 (d, J = 12.6 Hz, 2H),
3.73ꢀ3.68 (m, 4H), 3.17ꢀ3.12 (m, 1H), 3.17ꢀ3.12 (m, 1H), 2.16ꢀ2.09 (m, 1H), 1.89ꢀ1.84 (m, 2H),
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1.45, 1.29 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 138.5, 137.3, 128.8, 128.5 (2C),
128.4 (2C), 127.9 (2C), 127.7 (2C), 127.1 (2C), 111.6, 105.0, 82.6, 82.2, 81.3, 72.1, 60.6, 40.4,
34.6, 26.7, 26.1; Anal. Calcd. for C24H30O5S: C, 66.95; H, 7.02; Found: C, 67.26; H, 7.31.
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Procedure for the synthesis of carbohydrate based benzotriazolemethanethione (3aꢀk) and
compounds 6, 7 & 9. A stirring solution of free alcohol (1aꢀk and 8) in dry CH2Cl2 was treated
with bisꢀbenzotriazole methanethiones 2 in presence of pyridine and Et3N under inert
atmosphere. After completion of reaction (monitored by TLC), the reaction mixture was in vacuo
concentrated. Extraction with CH2Cl2, washing with 10% Na2CO3, water and brine solution
followed by drying over anhydrous Na2SO4, the organic layer was concentrated under reduced
pressure. Further purification using flash column chromatography using gradient mixtures of
ethyl acetate and nꢀhexane afforded pure benzotriazole methanethiones.
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6ꢀOꢀ(1,2:3,4ꢀDiꢀOꢀisopropylidineꢀαꢀ ꢀgalactopyranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3a): A stirring solution of compound 1a (1.93 g, 7.43 mmol) in dry CH2Cl2 (10
mL) was added with 2 (2.50 g, 8.92 mmol), pyridine (179 ꢁL, 2.23 mmol) and triethyl amine
(206 ꢁL, 1.49 mmol) under inert atmosphere. White crystals, 2.8 g, yield 90%, mp 110ꢀ112°C; Rf
1
= 0.6 (30% ethyl acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 8.41 (d, J = 8.4 Hz, 1H),
8.11 (d, J = 8.4 Hz, 1H), 7.64 (dd, J = 7.8, 7.5 Hz, 1H), 7.48 (dd, J = 7.8, 7.5 Hz, 1H), 5.64 (d, J
= 5.1 Hz, 1H), 5.03ꢀ4.98 (m, 1H), 4.92ꢀ4.85 (m, 1H), 4.71 (dd, J = 2.4, 7.2 Hz, 1H), 4.42ꢀ4.37
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(m, 3H), 1.56, 1.54, 1.50, 1.38 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 183.0, 146.3,
130.7, 130.5, 125.9, 120.4, 115.4, 110.0, 109.0, 96.3, 72.2, 70.9, 70.7, 70.8, 65.7, 26.0, 25.9,
24.9, 24.4; IR (KBr) νmax 1595, 1068, 1002, 989, 962, 888, 777, 744 cmꢀ1; MS: m/z 422 [M+H]+;
Anal. Calcd. for C19H23N3O6S: C, 54.14; H, 5.50; N, 9.98; Found: C, 53.75; H, 5.76; N, 9.61.
3ꢀOꢀ(1,2:5,6ꢀDiꢀOꢀisopropylidineꢀαꢀ ꢀglucofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3b): A stirring solution of compound 1b (20.0 g, 76.84 mmol) in dry CH2Cl2 (160
mL) was added with 2 (23.7 g, 84.52 mmol), pyridine (1.66 mL, 15.37 mmol) and Et3N (2.14 ml,
15.37 mmol) under inert atmosphere. Liquid, 28.8 g, yield 89%; Rf = 0.6 (30% ethyl acetate/nꢀ
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hexane); 1H NMR (300 MHz, CDCl3): δ 8.47 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.69
(t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 6.03 (d, J = 3.0 Hz, 2H), 4.84 (d, J = 3.6 Hz, 1H),
4.50ꢀ4.57 (m, 1H), 4.40ꢀ4.23 (m, 1H), 4.11ꢀ4.22 (m, 2H), 1.60, 1.42, 1.36, 1.25 (each s, each
3H); 13C NMR (75 MHz, CDCl3): δ 181.1, 146.4, 131.5, 130.6, 126.1, 120.7, 114.6, 112.6,
109.4, 105.1, 84.1, 82.7, 79.8, 72.1, 67.2, 26.9, 26.5, 26.1, 25.0; IR (Nujol) νmax 1610,
1590,1066, 984, 986, 973, 954, 732 cmꢀ1; MS: m/z 422 [M+H]+; Anal. Calcd. for C19H23N3O6S:
C, 54.14; H, 5.50; N, 9.98; Found: C, 54.51; H, 5.87; N, 9.66.
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3ꢀOꢀ(1,2:5,6ꢀDiꢀOꢀisopropylidineꢀαꢀ ꢀallofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3c): A stirring solution of compound 1c (1.0 g, 3.84 mmol) in dry CH2Cl2 (10
mL) was added with 2 (1.29 g, 4.61 mmol), pyridine (92 ꢁL, 1.15 mmol) and Et3N (107 ꢁL, 0.77
mmol) under inert atmosphere. White solid, 1.41 g, yield 87%, mp 82ꢀ84°C; Rf = 0.6 (30% ethyl
1
acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 8.46 (d, J = 8.1 Hz, 1H), 8.13 (d, J = 8.4 Hz,
1H), 7.66 (two d’s merged, J = 7.8, 7.5 Hz, 1H), 7.51 (two d’s merged, J = 7.8, 7.2 Hz, 1H), 5.96
(d, J = 3.6 Hz, 1H), 5.72 (dd, J = 5.1, 8.1 Hz, 1H), 5.18 (dd, J = 3.9, 8.7 Hz, 1H), 4.56 (dd, J =
4.5, 8.4 Hz, 1H), 4.44 (d, J = 4.8 Hz, 1H), 4.14ꢀ4.09 (m, 2H), 1.57, 1.39, 1.34, 1.32 (each s, each
3H); 13C NMR (75 MHz, CDCl3): δ 181.5, 146.4, 131.4, 130.4, 126.1, 120.6, 114.9, 113.6,
110.1, 104.2, 79.1, 77.6, 76.5, 74.5, 65.7, 26.7, 26.5, 26.2, 24.6; IR (KBr) νmax 1614, 1593,1103,
1121, 996, 962, 741 cmꢀ1; MS: m/z 422 [M+H]+; Anal. Calcd. for C19H23N3O6S: C, 54.14; H,
5.50; N, 9.98; Found: C, 54.34; H, 5.28; N, 9.63.
6ꢀOꢀ(3ꢀOꢀBenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ ꢀxylofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3d): A stirring solution of compound 1d (730 mg, 2.60 mmol) in dry CH2Cl2 (10
mL) was added with 2 (875 mg, 3.13 mmol), pyridine (63 ꢁL, 0.78 mmol) and Et3N (71 ꢁL, 0.53
mmol) under inert atmosphere. White solid, 991 mg, yield 86%, mp 90ꢀ92°C; Rf = 0.6 (20%
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ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 8.34 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.1
Hz, 1H), 7.64 (two d’s merged, J = 7.5, 7.8 Hz, 1H), 7.48 (two d’s merged, J = 8.1 Hz, 1H),
7.29ꢀ7.13 (m, 5H), 6.04 (d, J = 3.3 Hz, 1H), 5.07ꢀ4.94 (m, 2H), 4.74 (d, J = 12.0 Hz, 2H), 4.70
(d, J = 3.6 Hz, 1H), 4.51 (d, J = 12.0 Hz, 1H), 4.16 (d, J = 2.7 Hz, 1H), 1.52, 1.36 (each s, each
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3H); C NMR (75 MHz, CDCl3): δ 182.6, 146.3, 136.8, 131.2, 130.5, 128.4 (2C), 128.0, 127.8
(2C), 125.9, 120.5, 114.9, 112.1, 105.4, 82.2, 81.3, 77.1, 72.0, 70.3, 26.9, 26.2; IR (KBr) νmax
1618, 1595,1072, 1060, 992, 983, 974, 756 cmꢀ1; MS: m/z 442 [M+H]+; Anal. Calcd. for
C22H23N3O5S: C, 59.85; H, 5.25; N, 9.52; Found: C, 60.32; H, 4.81; N, 9.17.
5ꢀOꢀ(3ꢀOꢀBenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ ꢀribofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3e): A stirring solution of compound 1e (925 mg, 3.30 mmol) in dry CH2Cl2 (10
mL) was added with 2 (1.11 g, 3.96 mmol), pyridine (80 ꢁL, 0.99 mmol) and Et3N (67 ꢁL, 0.66
mmol) under inert atmosphere. Liquid, 1.27 g, yield 87%; Rf = 0.6 (20% ethyl acetate/nꢀhexane);
1H NMR (300 MHz, CDCl3): δ 8.36 (d, J = 7.8 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H), 7.63 (two d’s
merged, J = 7.8, 7.5 Hz, 1H), 7.49 (two d’s merged, J = 7.8 Hz, 1H), 7.29 (d, J = 7.2 Hz, 2H),
7.13 (t, J = 7.5 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H), 5.85 (d, J = 3.3 Hz, 1H), 4.98 (d, J = 11.7 Hz,
1H), 4.82 (d, J = 12.0 Hz, 1H), 4.77 (d, J = 3.3, 12.0 Hz, 1H), 4.70 (m, 1H), 4.52 (d, J = 12.0
Hz, 1H), 4.47 (m, 1H), 3.99 (dd, J = 3.9, 9.0 Hz, 1H), 1.64, 1.40 (each s, each 3H); 13C NMR (75
MHz, CDCl3): δ 182.4, 146.3, 136.9, 130.4, 128.3 (2C), 128.0 (3C), 127.9, 125.9, 120.5, 114.8,
113.3, 104.1, 77.0 (2C), 75.8, 72.4, 70.4, 26.8, 26.4; IR (Nujol) νmax 1625, 1590, 1162, 1140,
997, 981, 962, 754 cmꢀ1; MS: m/z 442 [M+H]+; Anal. Calcd. for C22H23N3O5S: C, 59.85; H, 5.25;
N, 9.52; Found: C, 59.59; H, 4.80; N, 9.91.
3ꢀOꢀ(5ꢀOꢀBenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ ꢀxylofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3f): A stirring solution of compound 1f (947 mg, 3.38 mmol) in dry CH2Cl2 (10
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mL) was added with 2 (1.14 g, 4.05 mmol), pyridine (81 ꢁL, 1.01 mmol) and Et3N (91 ꢁL, 0.68
mmol) under inert atmosphere. Liquid, 1.16 g, yield 78%; Rf = 0.7 (30% ethyl acetate/nꢀhexane);
1H NMR (300 MHz, CDCl3): δ 8.22 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.62 (two d’s
merged, J = 7.8, 7.5 Hz, 1H), 7.49 (two d’s merged, J = 7.8, 7.2 Hz, 1H), 7.14 (d, J = 6.9 Hz,
2H), 7.04 (dd, J = 7.2, 7.5 Hz, 2H), 6.96 (d, J = 7.2 Hz, 1H), 6.11 (d, J = 2.4 Hz, 1H), 6.06 (d, J
= 3.6 Hz, 1H), 4.81 (d, J = 3.6 Hz, 1H), 4.71 (m, 1H), 4.57ꢀ4.51 (m, 1H), 4.36 (d, J = 11.7 Hz,
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1H), 3.87ꢀ3.85 (m, 2H), 1.58, 1.35 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 181.2,
146.2, 137.1, 130.6, 128.3, 127.9 (2C), 127.7 (2C), 127.4, 126.0, 120.6, 114.5, 112.5, 104.7,
83.9, 82.6, 77.5, 73.3, 65.9, 26.4, 26.1; IR (Nujol) νmax 1627, 1591,1098, 1078, 1063, 1012, 996,
964, 736 cmꢀ1; MS: m/z 442 [M+H]+; Anal. Calcd. for C22H23N3O5S: C, 59.85; H, 5.25; N, 9.52;
Found: C, 60.21; H, 5.67; N, 9.11.
3ꢀOꢀ(5ꢀOꢀBenzoylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ ꢀxylofuranose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
carbothioate (3g): A stirring solution of compound 1g (1.04 g, 3.54 mmol) in dry CH2Cl2 (10
mL) was added with 2 (1.19 g, 4.25 mmol), pyridine (85 ꢁL, 1.06 mmol) and Et3N (98 ꢁL, 0.71
mmol) under inert atmosphere. White solid, 1.3 g, yield 82%, mp 94ꢀ96°C; Rf = 0.7 (30% ethyl
1
acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 8.34 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 8.1 Hz,
1H), 7.95 (d, J = 7.5 Hz, 2H), 7.66 (two d’s merged, J = 7.5, 7.8 Hz, 1H), 7.49 (t, J = 7.5 Hz,
2H), 7.35 (t, J = 7.5 Hz, 2H), 6.21 (s, 1H), 6.14 (d, J = 3.3 Hz, 1H), 4.88ꢀ4.84 (m, 2H), 4.72 (m,
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2H), 1.36, 1.23 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 181.1, 165.9, 146.4, 133.1,
131.3, 130.8 (2C), 129.6 (2C), 129.2, 128.2, 126.2, 120.8, 114.5, 112.7, 104.9, 83.8, 82.8, 76.9,
61.3, 26.5, 26.1; IR (KBr) νmax 1744, 1616, 1579,1088, 1067, 1054, 986, 974, 734 cmꢀ1; MS: m/z
456 [M+H]+; Anal. Calcd. for C22H21N3O6S: C, 58.01; H, 4.65; N, 9.23; Found: C, 57.61; H,
5.02; N, 9.54.
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D
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carbothioate (3h): A stirring solution of compound 1h (1.01 g, 4.94 mmol) in dry CH2Cl2 (10
mL) was added with 2, pyridine (119 ꢁL, 1.48 mmol) and Et3N (137 ꢁL, 0.99 mmol) under inert
atmosphere. White solid, 1.5 g, yield 87%, mp 88ꢀ90°C; Rf = 0.6 (30% ethyl acetate/nꢀhexane);
1H NMR (300 MHz, CDCl3): δ 8.43 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 7.8 Hz, 1H), 7.68 (t, J = 7.5
Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 5.08 (s, 1H), 4.70ꢀ4.91 (m, 3H), 4.43ꢀ4.50 (m, 2H), 3.35 (s,
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3H), 1.53, 1.35 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 194.7, 182.5, 146.4, 130.6,
126.0, 120.6, 114.8, 112.6, 109.3, 85.0, 83.3, 81.6, 72.7, 55.0, 26.3, 24.8; IR (KBr) νmax 1615,
1587, 1132, 1113, 976, 961, 954, 727 cmꢀ1; MS: m/z 366 [M+H]+; Anal. Calcd. for
C16H19N3O5S: C, 52.59; H, 5.24; N, 11.50; Found: C, 53.02; H, 5.62; N, 11.94.
5ꢀOꢀ(6ꢀOꢀBenzoylꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ ꢀglucofuranose)ꢀ1Hꢀ
D
benzo[d][1,2,3]triazoleꢀ1ꢀcarbothioate (3i): A stirring solution of compound 1i (910 mg, 2.20
mmol) in dry CH2Cl2 (10 mL) was added with 2 (738 mg, 2.63 mmol), pyridine (53 ꢁL, 0.66
mmol) and Et3N (61 ꢁL, 0.44 mmol) under inert atmosphere. Liquid, 947 mg, yield 75%; Rf =
0.7 (30% ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 8.20 (d, J = 8.4 Hz, 1H), 8.01
(d, J = 8.1 Hz, 1H), 7.88 (d, J = 7.2 Hz, 2H), 7.51ꢀ7.25 (m, 5H), 7.10ꢀ7.01 (m, 3H), 6.87 (t, J =
7.2 Hz, 2H), 6.17 (s, 1H), 5.93 (s, 1H), 5.18ꢀ5.11 (m, 1H), 4.82 (m, 1H), 4.61 (m, 2H), 4.53 (d, J
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= 11.4 Hz, 1H), 4.27 (d, J = 11.4 Hz, 1H), 4.14 (s, 1H), 1.43, 1.26 (each s, each 3H); C NMR
(75 MHz, CDCl3): δ 181.2, 165.9, 146.3, 136.0, 133.0, 131.4, 130.3, 129.7, 129.5, 128.3, 128.2,
128.0, 127.7, 125.9, 120.4, 114.8, 112.2, 105.4, 81.7, 80.1, 77.4, 77.2, 71.8, 68.6, 62.6, 26.8,
26.2; IR (Nujol) νmax 1739, 1631, 1588, 1121, 1103, 993, 972, 960, 853, 731 cmꢀ1; MS: m/z 576
[M+H]+; Anal. Calcd. for C30H29N3O7S: C, 62.60; H, 5.08; N, 7.30; Found: C, 62.91; H, 5.47; N,
7.64.
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6ꢀOꢀ(Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀαꢀ ꢀglucopyranoside)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀ
D
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carbothioate (3j): A stirring solution of compound 1j (1.21 g, 2.60 mmol) in dry CH2Cl2 (10
mL) was added with 2 (874 mg, 3.12 mmol), pyridine (60 ꢁL, 0.75 mmol) and Et3N (72 ꢁL, 0.52
mmol) under inert atmosphere. White solid, 1.3 g, yield 82%, mp 108ꢀ110°C; Rf = 0.7 (30%
ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 8.33 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 8.1
Hz, 1H), 7.55 (two d’s merged, J = 7.8, 7.4 Hz, 1H), 7.48 (two d’s merged, J = 7.8, 7.4 Hz, 1H),
7.37ꢀ7.04 (m, 15 H), 5.03 (d, J = 10.8 Hz, 1H), 4.87ꢀ4.71 (m, 5H), 4.71ꢀ4.61 (m, 3H), 4.06 (d, J
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= 8.7 Hz, 2H), 3.66 (d, J = 9.1 Hz, 1H), 3.61 (dd, J = 10.2, 9.3 Hz, 1H), 3.42 (s, 3H); C NMR
(75 MHz, CDCl3): δ 182.4, 146.3, 138.4, 137.9, 137.4, 131.2, 130.2, 128.4 (4C), 128.3 (4C),
128.1 (2C), 127.9 (2C), 127.7 (2C), 127.6, 125.8, 120.5, 114.7, 98.2, 82.1, 79.8, 76.4, 75.8, 74.8,
73.4, 71.5, 68.1, 55.5; IR (KBr) νmax 1739, 1631, 1588, 1121, 1103, 993, 972, 960, 853, 731 cmꢀ
1; MS: m/z 626 [M+H]+; Anal. Calcd. for C35H35N3O6S: C, 67.18; H, 5.64; N, 6.72; Found: C,
67.64; H, 5.27; N, 7.03.
7ꢀOꢀ(3ꢀOꢀBenzylꢀ5ꢀbenzylthioꢀ5,6ꢀdideoxyꢀ1,2ꢀOꢀisoproyledeneꢀαꢀ ꢀxyloꢀ
D
heptofuranuronose)ꢀ1Hꢀbenzo[d][1,2,3]triazoleꢀ1ꢀcarbothioate (3k): A stirring solution of
compound 1k (802 mg, 1.86 mmol) in dry CH2Cl2 (10 mL) was added with 2 (874 mg, 2.24
mmol), pyridine (60 ꢁL, 0.56 mmol) and Et3N (51 ꢁL, 0.37 mmol) under inert atmosphere.
White solid, 892 mg, Yield 81%, mp 94ꢀ96 °C; Rf = 0.6 (30% ethyl acetate/nꢀhexane); 1H NMR
(300 MHz, CDCl3): δ 8.24 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.57 (two d’s merged, J
= 7.2, 7.8 Hz, 1H), 7.46 (two d’s merged, J = 7.5, 6.9 Hz, 1H), 7.27 (m, 5H), 7.09ꢀ7.02 (m, 5H),
5.94 (s, 1H), 4.91 (m, 1H), 4.71 (d, J = 11.7 Hz, 2H), 4.61ꢀ4.55 (m, 2H), 4.19ꢀ4.15 (m, 2H), 3.70
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(s, 2H), 3.24 (m, 1H), 2.64 (m, 1H), 2.0 (m, 1H), 1.47, 1.31 (each s, each 3H); C NMR (75
MHz, CDCl3): δ 182.9, 146.3, 138.2, 137.2, 130.3, 128.7 (2C), 128.4 (4C), 127.9 (2C), 127.6,
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127.1 (2C), 125.7, 120.4, 115.0, 111.6, 105.1, 83.0, 82.1, 81.3, 71.9, 71.4, 39.3, 34.9, 30.6, 26.7,
26.1; IR (KBr) νmax 1734, 1640, 1580, 1127, 1110, 990, 970, 846, 737 cmꢀ1; MS: m/z 592
[M+H]+; Anal. Calcd. for C31H33N3O5S2: C, 62.92; H, 5.62; N, 7.10; Found: C, 63.35; H, 5.5.28;
N, 7.57.
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5ꢀ(1׳HꢀBenzo[1׳,2׳,3׳]triazolꢀ1׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ5ꢀdeoxyꢀ1,2ꢀOꢀisopropylideneꢀαꢀ
Dꢀ
glucofuranose
(6)
and
5ꢀ(2׳HꢀBenzo[1׳,2׳,3׳]triazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ5ꢀdeoxyꢀ1,2ꢀOꢀ
isopropylideneꢀαꢀDꢀglucofuranose (7): A stirring solution of compound 5 (1.15 g, 3.73 mmol)
in dry CH2Cl2 (12 mL) was added with 2 (1.25 g, 4.48 mmol), pyridine (90 ꢁL, 1.12 mmol) and
Et3N (103 ꢁL, 0.75 mmol) under inert atmosphere.
5ꢀ(1׳HꢀBenzo[1׳,2׳,3׳]triazolꢀ1׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ5ꢀdeoxyꢀ1,2ꢀOꢀisopropylideneꢀαꢀ
ꢀ
D
glucofuranose (6): Colorless crystals, mp 158ꢀ160°C; Rf = 0.6 (30% ethyl acetate/nꢀhexane); 1H
NMR (300 MHz, CDCl3): δ 8.15 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 7.61 (two d’s
merged, J = 6.9, 8.7 Hz, 1H), 7.50 (two d’s merged, J = 7.8, 6.9 Hz, 1H), 7.19ꢀ7.09 (m, 3H),
6.91 (d, J = 7.2 Hz, 2H), 6.12 (d, J = 3.3 Hz, 1H), 5.56 (d, J = 3.3 Hz, 1H), 5.37 (d, J = 11.1 Hz,
1H), 5.28 (d, J = 11.1 Hz, 1H), 4.62 (d, J = 3.0 Hz, 1H), 4.40 (d, J = 10.8 Hz, 1H), 4.15 (d, J =
10.8 Hz, 1H), 4.14 (d, J = 2.7 Hz, 1H), 1.55, 1.35 (each s, each 3H); 13C NMR (75 MHz,
CDCl3): δ 187.9, 148.5, 135.7, 129.6, 128.4, 128.1, 125.3, 120.9, 113.2, 110.3, 105.9, 82.2, 81.8,
80.1, 73.0, 72.7, 27.1, 26.4; IR (KBr) νmax 1610, 1589, 1108, 1075, 1025, 975, 926, 741, 696 cmꢀ
1; MS: m/z 470 [M+H]+; Anal. Calcd. for C23H23N3O6S: C, 58.84; H, 4.94; N, 8.95; Found: C,
58.55; H, 5.25; N, 9.31.
5ꢀ(2׳HꢀBenzo[1׳,2׳,3׳]triazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ5ꢀdeoxyꢀ1,2ꢀOꢀisopropylideneꢀαꢀ
ꢀ
D
glucofuranose (7): Colorless crystals, mp 162ꢀ164°C; Rf = 0.6 (30% ethyl acetate/nꢀhexane); 1H
NMR (300 MHz, CDCl3): δ 7.81 (d, J = 6.6 Hz, 1H), 7.80 (d, J = 6.3 Hz, 1H), 7.45 (d, J = 6.6
Hz, 1H), 7.44 (d, J = 6.6 Hz, 1H), 76.95ꢀ6.84 (m, 3H), 6.62 (d, 2H), 6.13 (d, J = 2.7 Hz, 1H),
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(d, J = 11.7 Hz, 1H), 4.33 (s, 1H), 3.87 (d, J = 11.7 Hz, 1H), 1.62, 1.39 (each s, each 3H); C
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NMR (75 MHz, CDCl3): δ 188.3, 144.5, 134.9, 128.27, 128.21, 128.1, 128.0, 118.8, 113.2,
106.0, 100.7, 81.6, 81.0, 80.0, 73.8, 72.0, 27.1, 26.4; IR (KBr) νmax 1562, 1455, 1071, 1036, 994,
967, 876, 847, 753, 696, 641 cmꢀ1; MS: m/z 470 [M+H]+; Anal. Calcd. for C23H23N3O6S: C,
58.84; H, 4.94; N, 8.95; Found: C, 58.47; H, 4.69; N, 8.62.
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OꢀCholesterylꢀ(1Hꢀbenzo[1׳,2׳,3׳]triazolꢀ1׳ꢀyl)methanethione (9): A stirring solution of
compound 8 (1.50 g, 3.88 mmol) in dry CH2Cl2 (10 mL) was added with 2 (1.30 g, 4.66 mmol),
pyridine (93 ꢁL, 1.17 mmol) and Et3N (108 ꢁL, 0.78 mmol) under inert atmosphere. White
crystals, 1.66 g, yield 78%; mp 170ꢀ172°C; Rf = 0.7 (30% ethyl acetate/nꢀhexane); 1H NMR (300
MHz, CDCl3): δ 8.38 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.65 (two d’s merged, J = 7.2,
7.8 Hz, 1H), 7.49 (t, J = 7.0 Hz, 1H), 5.50 (m, 2H), 2.72 (d, J = 7.5 Hz, 2H), 2.26 (m, 1H), 2.02ꢀ
1.83 (m, 5H), 1.56ꢀ1.52 (m, 9H), 1.33ꢀ1.01 (m, 14H), 0.93 (d, J = 9.3 Hz, 3H), 0.87 (s, 3H), 0.85
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(s, 3H), 0.73 (s, 3H); C NMR (75 MHz, CDCl3): δ 182.2, 146.4, 138.6, 131.3, 130.2, 125.8,
123.8, 120.5, 114.9, 83.8, 56.6, 56.1, 49.9, 42.2, 39.6, 39.4, 37.3, 36.8, 36.6, 36.1, 35.7, 31.9,
31.8, 28.1, 27.9, 27.1, 24.2, 23.8, 22.7, 22.5, 21.0, 19.3, 18.7, 11.8; IR (KBr) νmax 1611, 1070,
1021, 974, 723, 685 cmꢀ1; MS: m/z 548 [M+H]+; Anal. Calcd. for C34H49N3OS: C, 74.54; H,
9.02; N, 7.67; Found: C, 74.87; H, 9.41; N, 8.07.
Procedure for the synthesis of glycoconjugate benzothiazoles (4aꢀk) and compound 10:
A stirring solution of benzotriazolemethanethione (3aꢀk & 9) in toluene was added with
stannanyl/silyl hydride (2.0 equiv) and AIBN (5 mol %) under inert atmosphere. The reaction
stirred under heating at 80 °C as well as exposure to microwave CEM Discover® LabMate at
100°C. After completion of reaction (monitored by TLC), the reaction mixture was in vacuo
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concentrated, extracted with CH2Cl2 and washed with 10% LiOH, water and brine solutions.
After drying over anhydrous Na2SO4, the organic layer was in vacuo concentrated. Purification
using flash column chromatography afforded glycoconjugate benzothiazoles.
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6ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ1,2:3,4ꢀdiꢀOꢀisopropylidineꢀαꢀ
ꢀgalactopyranose (4a): A stirring
D
solution of 3a (400 mg, 0.95 mmol) in toluene was added with tributyltin hydride (0.55 mL, 1.90
mmol) and AIBN (5 mol%) under inert atmosphere. White crystals, 365 mg, yield 98%, mp 100ꢀ
1
102°C; Rf = 0.8 (20% ethyl acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 7.64 (t, J = 8.7
Hz, 2H), 7.34 (dd, J = 7.2, 7.5 Hz, 1H), 7.22 (two d’s merged, J = 7.5, 7.2 Hz, 1H), 5.57 (d, J =
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4.8 Hz, 1H), 4.79ꢀ4.73 (m, 3H), 4.69ꢀ4.64 (m, 3H), 1.48, 1.48, 1.35, 1.32 (each s, each 3H); C
NMR (75 MHz, CDCl3): δ 172.5, 149.1, 132.0, 125.8, 123.4, 121.2, 120.8, 109.6, 108.8, 96.3,
70.9, 70.6, 70.4, 70.2, 65.5, 25.9, 25.9, 24.9, 24.4; IR (KBr) νmax 1597, 1536, 1067, 1007, 959,
891, 728, 692, 650 cmꢀ1; MS: m/z 394 [M+H]+; Anal. Calcd. for C19H23NO6S: C, 58.00; H, 5.89;
N, 3.56; Found: C, 58.29; H, 5.51; N, 3.33.
3ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ1,2;5,6ꢀDiꢀOꢀisopropylidineꢀαꢀ
ꢀglucofuranose (4b): A stirring
D
solution of 3b (10.0 g, 23.72 mmol) in toluene was added with tributyltin hydride (12.76 ml,
47.45 mmol) and AIBN (5 mol%) under inert atmosphere. Liquid, 8.86 g, yield 95%; Rf = 0.7
(20% ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 7.74 (d, J = 9.1 Hz, 1H), 7.64 (d,
J = 9.1 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H), 5.95 (d, J = 3.6 Hz, 1H), 5.63
(d, J = 2.4 Hz, 1H), 4.83 (d, J = 3.6 Hz, 1H), 4.32ꢀ4.45 (m, 2H), 4.05ꢀ4.15 (m, 2H), 1.56, 1.42,
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1.33, 1.30 (each s, each 3 H); C NMR (75 MHz, CDCl3): δ 171.1, 149.0, 132.0, 126.0, 123.8,
121.0, 112.3, 109.3, 105.0, 82.9, 82.6, 79.8, 72.2, 67.0, 26.8, 26.7, 26.2, 25.2; IR (Nujol) νmax
1598, 1535, 1075, 1021, 845, 756, 644 cmꢀ1; MS: m/z 394 [M+H]+; Anal. Calcd. for
C19H23NO6S: C, 58.00; H, 5.89; N, 3.56; Found: C, 58.35; H, 6.22; N, 3.91.
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3ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ1,2:5,6ꢀdiꢀOꢀisopropylidineꢀαꢀ
Dꢀallofuranose (4c):
A
stirring
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7
8
solution of 3c (300 mg, 0.71 mmol) in toluene was added with tributyltin hydride (0.38 mL, 1.42
mmol) and AIBN (5 mol%) under inert atmosphere. White solid, 268 mg, yield 96%, mp 78ꢀ
80°C; Rf = 0.6 (20% ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 7.66 (t, J = 8.7 Hz,
2H), 7.35 (d, J = 7.5 Hz, 1H), 7.25 (d, J = 7.2, 1H), 5.90 (d, J = 3.3, 1H), 5.38 (dd, J = 5.1, 8.4
Hz, 1H), 5.13 (t, J = 4.2, 1H), 4.40ꢀ4.32 (m, 2H), 4.09 (d, J = 6.6 Hz, 1H), 4.00 (d, J = 5.7 Hz,
1H), 1.59, 1.39, 1.33, 1.33 (each s, each 3H); 13C NMR (75 MHz, CDCl3): δ 171.2, 148.9, 132.3,
125.9, 123.7, 121.3, 121.0, 113.3, 109.9, 104.0, 78.3, 77.5, 77.4, 74.9, 65.4, 26.6, 26.1, 25.0; IR
(KBr) νmax 1596, 1536, 1073, 1023, 851, 755, 639 cmꢀ1; MS: m/z 394 [M+H]+; Anal. Calcd. for
C19H23NO6S: C, 58.00; H, 5.89; N, 3.56; Found: C, 57.73; H, 6.23; N, 3.17.
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5ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ
ꢀxylofuranose (4d): A stirring
D
solution of 3d (400 mg, 0.91 mmol) in toluene was added with tributyltin hydride (0.49 mL, 1.81
mmol) and AIBN (5 mol%) under inert atmosphere. Liquid, 352 mg, yield 94%; Rf = 0.7 (20%
ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 7.67 (d, J = 8.1 Hz, 1H), 7.62 (d, J = 7.8
Hz, 1H), 7.37ꢀ7.19 (m, 7H), 6.00 (d, J = 3.6 Hz, 1H), 4.88 (dd, 1H), 4.79 (d, J = 6.6 Hz, 1H),
4.74 (d, J = 12.9 Hz, 1H), 4.68ꢀ4.64 (m, 2H), 4.54 (d, J = 12.0 Hz, 1H), 4.08 (d, J = 3.0 Hz, 1H),
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1.50, 1.33 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 172.3, 149.1, 137.0, 132.0, 128.4,
127.9, 127.7, 125.9, 123.5, 121.2, 120.8, 111.9, 105.2, 82.1, 81.5, 77.9, 71.9, 68.9, 26.8, 26.2; IR
(Nujol) νmax 1598, 1537, 1113, 1067, 968, 912, 784, 737, 649 cmꢀ1; MS: m/z 414 [M+H]+; Anal.
Calcd. for C22H23NO5S: C, 63.91; H, 5.61; N, 3.39; Found: C, 64.27; H, 5.29; N, 3.62.
5ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ
ꢀribofuranose (4e): A stirring
D
solution of 3e (400 mg, 0.91 mmol) in toluene was added with tributyltin hydride (0.49 mL, 1.81
mmol) and AIBN (5 mol%) under inert atmosphere. Liquid, 355 mg, yield 95%; Rf = 0.7 (20%
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ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 7.67 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 7.8
Hz, 1H), 7.39ꢀ7.20 (m, 7H), 5.79 (d, J = 3.3 Hz, 1H), 4.83ꢀ4.75 (m, 2H), 4.66 (dd, J = 4.2, 11.7
Hz, 1H), 4.61 (dd, J = 3.6, 7.5 Hz, 1H), 4.56 (d, J = 11.7 Hz, 1H), 4.39 (d, J = 6.6 Hz, 1H), 3.85
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(dd, J = 4.2, 9.0 Hz, 1H), 1.63, 1.38 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 172.5,
149.0, 137.1, 132.0, 128.4, 127.9, 125.9, 123.5, 121.2, 120.8, 113.2, 104.2, 72.3, 69.4, 26.8,
26.5; IR (Nujol) νmax 1596, 1531, 1107, 1055, 914, 774, 736, 650 cmꢀ1; MS: m/z 414 [M+H]+;
Anal. Calcd. for C22H23NO5S: C, 63.91; H, 5.61; N, 3.39; Found: C, 63.46; H, 5.98; N, 3.83.
5ꢀOꢀBenzylꢀ3ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ1,2ꢀOꢀisopropylidineꢀαꢀ
ꢀxylofuranose (4f): A stirring
D
solution of 3f (364 mg, 0.82 mmol) in toluene was added with tributyltin hydride (0.48 mL, 1.65
mmol) under inert atmosphere. Liquid, 330 mg, yield 97%; Rf = 0.7 (20% ethyl acetate/hexane);
1H NMR (300 MHz, CDCl3): δ 7.63 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.28 (two d’s
merged, J = 7.8, 7.5 Hz, 1H), 7.14 (m, 6H), 5.91 (s, 1H), 5.60 (s, 1H), 4.72 (s, 1H), 4.51ꢀ4.70 (m,
2H), 4.36 (d, J = 12.0 Hz, 1H), 3.71 (two d’s merged, J = 2.4, 2.7 Hz, 2H), 1.47, 1.24 (each s,
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each 3H); C NMR (75 MHz, CDCl3): δ 171.1, 148.9, 137.6, 132.0, 128.2 (2C), 127.6 (2C),
127.6, 126.0, 123.8, 121.3, 121.2, 112.2, 104.8, 83.0, 82.7, 78.2, 73.5, 66.9, 26.6, 26.2; IR
(Nujol) νmax 1598, 1530, 1097, 1046, 923, 761, 732, 644 cmꢀ1; MS: m/z 414 [M+H]+; Anal.
Calcd. for C22H23NO5S: C, 63.91; H, 5.61; N, 3.39; Found: C, 64.25; H, 5.95; N, 3.66.
5ꢀOꢀBenzoylꢀ3ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ1,2ꢀOꢀisopropylidineꢀαꢀ
ꢀxylofuranose (4g): A stirring
D
solution of 3g (352 mg, 1.20 mmol) in toluene was added with tributyltin hydride (0.70 mL, 2.40
mmol) and AIBN (5 mol%) under inert atmosphere. White solid, 313 mg, yield 95%; mp 78ꢀ
80°C; Rf = 0.7 (20% ethyl acetate/nꢀhexane); 1H NMR (300 MHz, CDCl3): δ 7.92 (d, J = 8.1 Hz,
2H),7.61ꢀ7.42 (m, 3H), 7.36ꢀ7.29 (m, 3H), 7.18ꢀ7.14 (m, 1H), 5.99 (d, J = 2.7 Hz, 1H), 5.72 (s,
1H), 4.80 (d, J = 2.7 Hz, 1H), 4.69 (m, 1H), 4.57 (d, J = 5.7 Hz, 2H), 1.50, 1.33 (each s, each
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3H); 13C NMR (75 MHz, CDCl3): δ 171.1, 166.0, 148.7, 133.0, 132.0, 129.7, 129.5, 128.5,
128.2, 126.1, 123.9, 121.3, 112.4, 105.0, 83.0, 82.8, 77.1, 61.3, 26.5, 26.1; IR (KBr) νmax 1733,
1595, 1531, 1102, 987, 911, 749, 756, 645 cmꢀ1; MS: m/z 428 [M+H]+; Anal. Calcd. for
C22H21NO6S: C, 61.82; H, 4.95; N, 3.28; Found: C, 61.40; H, 5.34; N, 3.73.
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Methyl 5ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ2,3ꢀOꢀisopropylidineꢀβꢀ
ꢀribofuranoside (4h): A stirring
D
solution of 3h (408 mg, 1.12 mmol) in toluene was added with tributyltin hydride (0.60 mL, 2.23
mmol) and AIBN (5 mol%) under inert atmosphere. Liquid, 361 mg, yield 96%; Rf = 0.7 (20%
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ethyl acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 7.65 (two d’s merged, J = 8.1, 8.2 Hz,
2H), 7.36 (t, J = 7.4 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 5.03 (s, 1H), 4.79 (d, 1H), 4.59ꢀ4.67 (m,
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4H), 3.34 (s, 3H), 1.34, 1.50 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 172.3, 149.0,
132.0, 125.9, 123.6, 121.2, 120.9, 112.6, 109.4, 85.1, 83.9, 81.7, 71.4, 55.0, 26.4, 24.9; IR
(Nujol) νmax 1733, 1595, 1531, 1102, 987, 911, 749, 756, 645 cmꢀ1; MS: m/z 338 [M+H]+; Anal.
Calcd. for C16H19NO5S: C, 56.96; H, 5.68; N, 4.15; Found: C, 57.42; H, 5.36; N, 3.72.
6ꢀOꢀBenzoylꢀ5ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ1,2ꢀOꢀisopropylidineꢀαꢀ
ꢀglucofuranose
D
(4i): A stirring solution of 3i (381 mg, 0.66 mmol) in toluene was added with tributyltin hydride
(0.36 mL, 1.32 mmol) and AIBN (5 mol%) under inert atmosphere. Liquid, 347 mg, yield 96%;
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Rf = 0.8, 20% ethyl acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 7.95 (d, J = 7.2 Hz, 2H),
7.60ꢀ7.59 (m, 2H), 7.47 (m, 1H), 7.35ꢀ7.19 (m, 5H), 7.11ꢀ7.01 (m, 4H), 5.97 (s, 2H), 5.13 (d, J =
12.6 Hz, 1H), 4.66ꢀ4.56 (m, 4H), 4.38 (d, J = 11.1 Hz, 1H), 4.14 (s, 1H), 1.51, 1.34 (each s, each
3H); 13C NMR (75 MHz, CDCl3): δ 171.4, 166.0, 149.0, 136.6, 132.8, 132.0, 129.9, 129.7, 129.6,
128.3, 128.2, 128.1, 127.9, 127.8, 125.9, 123.5, 121.1 (2C), 112.1, 105.4, 81.8, 81.0, 77.8, 75.8,
72.3, 63.6, 26.8, 26.3; IR (Nujol) νmax 1742, 1596, 1530, 1114, 1075, 970, 911, 755, 736, 688,
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642 cmꢀ1; MS: m/z 548 [M+H]+; Anal. Calcd. for C30H29NO7S: C, 65.80; H, 5.34; N, 2.56;
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Methyl 6ꢀOꢀ(benzothiazolꢀ2׳ꢀyl)ꢀ2,3,4ꢀtriꢀOꢀbenzylꢀαꢀ
ꢀglucopyranoside (4j): A stirring
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solution of 3j (402 mg, 0.64 mmol) in toluene was added with tributyltin hydride (0.35 mL, 1.28
mmol) and AIBN (5 mol%) under inert atmosphere. White crystals, 357 mg, yield 92%, mp 88ꢀ
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90°C; Rf = 0.8 (20% ethyl acetate/nꢀhexane); H NMR (300 MHz, CDCl3): δ 7.64 (two d’s
merged, J = 8.7 Hz, 2H), 7.35ꢀ7.23 (m, 17H), 5.01 (d, J = 10.8 Hz, 1H), 4.89ꢀ4.66 (m, 4H), 4.69ꢀ
4.55 (m, 4H), 4.04 (t, J = 9.3 Hz, 1H), 3.95 (d, J = 9.9 Hz, 1H), 3.67ꢀ 3.57 (m, 2H), 3.39 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 172.5, 149.0, 138.5, 137.7, 131.9, 128.4 (4C), 128.3 (2C), 128.1
(2C), 128.0 (2C), 127.9 (2C), 127.8 (4C), 127.6, 125.9, 123.5, 121.2, 120.8, 98.1, 82.0, 79.8,
75.7, 75.1, 73.4, 70.0, 68.8, 55.3; IR (KBr) νmax 1596, 1564, 1534, 1115, 1065, 1013, 751, 738,
696, 653 cmꢀ1; MS: m/z 598 [M+H]+; Anal. Calcd. for C35H35NO6S: C, 70.33; H, 5.90; N, 2.34;
Found: C, 70.68; H, 6.27; N, 1.95.
7ꢀOꢀ(Benzothiazolꢀ2׳ꢀyl)ꢀ3ꢀOꢀbenzylꢀ5ꢀbenzylthioꢀ5,6ꢀdideoxyꢀ1,2ꢀOꢀisoproyledeneꢀαꢀ
ꢀ
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xyloꢀheptofuranuronose (4k): A stirring solution of 3k (400 mg, 0.68 mmol) in toluene was
added with tributyltin hydride (0.36 mL, 1.35 mmol) and AIBN (5 mol%) under inert
atmosphere. Liquid, 358 mg, yield 94%; Rf = 0.8 (20% ethyl acetate/nꢀhexane); 1H NMR (300
MHz, CDCl3): δ 7.66 (d, J = 8.1 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.24ꢀ7.08 (m, 12H), 5.89 (s,
1H), 4.68ꢀ4.54 (m, 5H), 4.12ꢀ4.08 (m, 2H), 3.73 (s, 2H), 3.23 (m, 1H), 2.47 (m, 1H), 2.07 (m,
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1H), 1.45, 1.29 (each s, each 3H); C NMR (75 MHz, CDCl3): δ 172.6, 149.3, 138.3, 137.3,
131.8, 128.7 (2C), 128.4 (4C), 127.8, 127.7 (2C), 126.9, 125.7, 123.2, 121.1, 120.6, 111.4, 105.0,
82.7, 82.2, 81.3, 72.1, 69.5, 39.7, 34.5, 30.7, 26.7, 26.1; IR (Nujol) νmax 1597, 1529, 1118, 1095,
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978, 932, 784, 764, 736, 654 cmꢀ1; MS: m/z 564 [M+H]+; Anal. Calcd. for C31H33NO5S2: C,
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66.05; H, 5.90; N, 2.48; Found: C, 65.72; H, 6.27; N, 2.07.
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OꢀCholesteryl benzothiazole (10): A stirring solution of 9 (407 mg, 0.74 mmol) in toluene was
added with tributyltin hydride (0.40 mL, 1.49 mmol) and AIBN (5 mol%) under inert
atmosphere. White crystals, 370 mg, yield 95%, mp 106ꢀ108°C; Rf = 0.7 (20% ethyl acetate/nꢀ
hexane); 1H NMR (300 MHz, CDCl3): δ 7.63 (two d’s merged, J = 8.7, 9.0 Hz, 2H), 7.33 (t, J =
7.5 Hz, 1H), 7.18 (two d’s merged, J = 7.8, 7.2 Hz, 1H), 5.45 (m, 1H), 5.01 (m, 1H), 2.68ꢀ2.64
(m, 1H), 2.53ꢀ2.45 (m, 1H), 2.16 (m, 1H), 2.04ꢀ1.69 (m, 5H), 1.57ꢀ0.85 (m, 32H), 0.68 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 172.2, 149.6, 139.3, 131.7, 125.8, 123.1, 123.1, 121.1, 120.6,
81.7, 56.6, 56.1, 50.0, 42.3, 39.7, 39.5, 38.1, 37.9, 36.6, 36.1, 35.7, 31.9, 31.8, 28.2, 28.0, 27.8,
24.2, 23.8, 22.8, 22.5, 22.0, 19.3, 18.7, 11.8; IR (KBr) νmax 1597, 1529, 1112, 1070, 731, 651 cmꢀ
1; MS: m/z 520 [M+H]+; Anal. Calcd. for C34H49NOS: C, 78.56; H, 9.51; N, 2.70; Found: C,
78.32; H, 9.19; N, 2.32.
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ACKNOWLEDGMENTS
Authors thank University Grant Commission (UGC) and Council of Scientific & Industrial
Research (CSIR) for the funding. We thank CISC, Banaras Hindu University for spectroscopic
studies and single crystal Xꢀray analysis.
Supporting Information
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Copies of H and C NMR spectra for all the new compounds and Xꢀray crystallographic data
for 3a, 4a, 6, 7, and 10 (CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.
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