Synthesis of novel triazolyl pyranochromen-2(1H)-ones and their antibacterial activity evaluation

Article abstract of DOI:10.1007/s00044-016-1549-3

A series of thirty-three novel triazolyl pyranochromen-2(1H)-one derivatives have been synthesized via Cu (I) catalysed Huisgen 1,3-dipolar cycloaddition reaction. All of the synthesized compounds have been fully characterized from their spectral data and evaluated for antibacterial activity against both gram-positive and gram-negative bacteria. The activity results revealed that amongst all the compounds screened, six compounds, i.e. 2-[4-(((7-ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (41), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-ethyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (44), 3-ethyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (46), 2-[4-(((7-hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid (52), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-3-hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (55) and 3-hexyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (57), exhibited moderate activity against all the strains studied with zone of inhibition between 10 and 16?mm and MIC values in the range of 75–170?μg/mL as compared to the standard used. The information obtained from structure–activity relationship can be used to design and develop the next generation of compounds with higher antibacterial efficacy.

Full text of DOI:10.1007/s00044-016-1549-3

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-016-1549-3
ORIGINAL RESEARCH
Synthesis of novel triazolyl pyranochromen-2(1H)-ones and their
antibacterial activity evaluation
Shiv Kumar1 Suchita Prasad1 Bipul Kumar2 Hemant K. Gautam2 Sunil K. Sharma1
•
•
•
•
Received: 16 May 2015 / Accepted: 25 February 2016
Ó Springer Science+Business Media New York 2016
Abstract A series of thirty-three novel triazolyl pyra-
nochromen-2(1H)-one derivatives have been synthesized
via Cu (I) catalysed Huisgen 1,3-dipolar cycloaddition
reaction. All of the synthesized compounds have been fully
characterized from their spectral data and evaluated for
antibacterial activity against both gram-positive and gram-
negative bacteria. The activity results revealed that
amongst all the compounds screened, six compounds, i.e.
2-[4-(((7-ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropyrano
[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]
acetic acid (41), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-
1,2,3-triazol-4-yl)methoxy]-3-ethyl-4,8,8-trimethyl-7,8-dihy-
dropyrano[3,2-g]chromen-2(6H)-one (44), 3-ethyl-4,8,8-tri-
methyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydrox-
ymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-4-yl)me-
thoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (46),
2-[4-(((7-hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropy-
rano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-
yl]acetic acid (52), 10-[(1-(1,3-dihydroxypropan-2-yl)-1H-
1,2,3-triazol-4-yl)methoxy]-3-hexyl-4,8,8-trimethyl-7,8-dihy-
dropyrano[3,2-g]chromen-2(6H)-one (55) and 3-hexyl-4,8,
8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-
(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-triazol-
4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one
(57), exhibited moderate activity against all the strains studied
with zone of inhibition between 10 and 16 mm and MIC
values in the range of 75–170 lg/mL as compared to the
standard used. The information obtained from structure–ac-
tivity relationship can be used to design and develop the next
generation of compounds with higher antibacterial efficacy.
Keywords Alkyl chain Á Antimicrobial activity Á
Pyranochromen-2-ones Á Polar groups Á Triazoles
Introduction
Heterocycles, a class of compounds of prime importance,
make up for about two-thirds of all known organic
compounds (Eftekhari-Sis and Zirak, 2015). They have
gained considerable interest because of their utility as
synthetic intermediates, their immense distribution in
natural products and indispensable presence in drugs
holds the essence of life (Horton et al., 2003). However,
with the advent of globalization and newer diseases
coming into the picture, a stimulated research in the field
of heterocyclic chemistry is required in order to trigger
the synthesis of therapeutic agents in the pharmaceutical
pipeline with higher efficacy.
Oxygen-containing heterocycles have acquired substan-
tial attention which stems from the fact that these are
important synthetic targets due to their ubiquity in natural
products, their wide range of biological activities and their
utility as versatile intermediates in organic synthesis (Liao
et al., 2006). Pyranocoumarins, a valuable class of oxygen-
containing heterocycles widely distributed in higher plants
such as Calophyllum lanigerium and Calophyllum teysma-
nii, possess versatile biological and pharmaceutical appli-
cations such as antipsoriasis, anticancer, antimycobacterium
Electronic supplementary material The online version of this
article (doi:10.1007/s00044-016-1549-3) contains supplementary
material, which is available to authorized users.
& Sunil K. Sharma
sksharma@chemistry.du.ac.in
1
Department of Chemistry, University of Delhi, Delhi 110007,
India
2
CSIR-Institute of Genomics and Integrative Biology,
Sukhdev Vihar, Mathura Road, Delhi 110025, India
123

Med Chem Res
tuberculosis, antifungal and antibacterial agents (Ahmed
and Babu, 2013). Luvangetin (1) has been identified as an
antidiabetic natural product, which belongs to this privi-
leged scaffold (Kumar et al., 2009). The literature reports
reveal that decursinol angelate (2) and decursin (3) isolated
from Angelica gigas roots exert a long-lasting inhibition of
androgen receptor (AR)—mediated signalling, crucial for
prostate cancer development and also exhibit potent
antibacterial activities against Bacillus subtilis (Lee et al.,
2003). Decursin (3) from Streptomyces sp. GMT-8, an
endophyte in Zingiber officinale Rosc., has been identified
as a significant antibacterial ingredient against gram-posi-
tive bacteria (Taechowisan et al., 2013). Pyranocoumarins
(4 & 5) isolated from Peucedanum praeruptorum Dunn
have been found to induce anti-inflammatory effects in
murine macrophages through the inhibition of NF-jB and
STAT3 activation (Yu et al., 2012) (Fig. 1). Thus, pyra-
nocoumarins represent a novel class of compounds that
warrant further investigation as potential therapeutic agents.
1,2,3-Triazolyl compounds have gained tremendous
importance in recent years as antibiotic, antimicrobial,
antimalarial, anticancer agents, etc. (Soltis et al., 1996;
Kaushik et al., 2013), besides their ease of synthesis via Cu
(I) catalysed Huisgen 1,3-dipolar cycloaddition of azides
and terminal alkynes (Finn and Fokin, 2010).
triazole and pyranochromen-2(1H)-one moieties and
observed the potential synergistic effect on the antibac-
terial efficacy.
Results and discussion
Chemistry
A series of thirty-three novel triazolyl pyranocoumarin
hybrids (25–57) were synthesized by Huisgen 1,3-dipolar
cycloaddition reaction of propargyloxy pyranochromen-2-
ones (13–15) with various aromatic/aliphatic/sugar/glyc-
erol azides (16–24) (Fig. 2) using Cu (I) as a catalyst
(Scheme 1). 1,2,3-Trihydroxybenzene (6) was used as a
key starting material for the synthesis of 4,8,8-trimethyl-
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (13)/3-ethyl-4,8,8-trimethyl-10-(prop-2-yn-1-
yloxy)-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (14)/3-
n-hexyl-4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihy-
dropyrano[3,2-g]chromen-2(6H)-one (15), the desired
acetylenic precursors of triazolyl pyranochromen-2-ones
(25–57).
Pyranochromen-2-ones bearing hydroxyl group at C-10
position (10–12) were synthesized by following two dif-
ferent protocols. In order to synthesize 10-hydroxy-4,8,8-
trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (10),
2,2-dimethylchroman-7,8-diol (7) was made to undergo
Pechmann condensation with ethyl 3-oxobutanoate in the
presence of sulphuric acid as a catalyst (Ahluwalia and Jolly,
1982). 2,2-Dimethylchroman-7,8-diol (7) used in the reac-
tion was in turn synthesized from the condensation reaction
between 1,2,3-trihydroxybenzene (6) and 2-methylbuta-1,3-
diene (isoprene) in the presence of orthophosphoric acid and
using xylene as a solvent (Scheme 1; Ahluwalia et al., 1982).
However, compound 7 on condensation with alkylated b-
ketoesters led to the formation of the desired products 3-alkyl-
10-hydroxy-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chro-
men-2(6H)-one (11/12) in very low yields.
Our research group has been actively involved in the
synthesis of coumarin and pyranocoumarin derivatives
and evaluation of their biological activities (Kathuria
et al., 2011; Chand et al., 2013, 2015; Vats et al., 2014;
Jalal et al., 2012). The incorporation of quaternary
ammonium and amido groups on quinolinones, chrome-
nones and pyranochromenones by our group has proved
to be a successful approach to yield promising antimi-
crobial agents (Gupta et al., 2012; Singh et al., 2012,
2014; Prasad et al., 2015). In the light of above literature
reports and in continuation of our efforts to come up with
newer and improved antibacterial agents, we herein have
synthesized a wide array of triazolyl pyranochromen-
2(1H)-one derivatives by combining together 1,2,3-
Fig. 1 Pyranocoumarins of
pharmaceutical importance
H
OC
3
O
O
O
O
O
O
O
O
O
O
O
O
O
3
2
1
O
O
O
O
O
O
O
O
O
O
O
O
4
5
123

Med Chem Res
R2
N3
R2
=
5"
5"
5"
NO
F
4"
6"
1"
1a
4"
3"
4"
2
O
6"
1"
1a
6"
1"
1a
2"
O
4"
6"
1""
2"
O
3"
3"
2""
3"
5"
1"
1"
2"
16
2"
18
2"
17
20
19
2"
2"
6''b
6''a,
3"
F
1"
6"
1"
3"
4"
1"
2"
5"
2"
OAc
3"
4"
OH
OH
23
4"
OAc
6"
1"
O
AcO
5"
22
3"
5"
21
OAc
24
Fig. 2 Structure of azides synthesized (16–24)
1
In order to overcome this difficulty, a different strategy
was employed wherein 1,2,3-trihydroxybenzene (6) was
initially condensed with ethyl 2-alkylacetoacetate under
Pechmann reaction conditions to yield 3-alkyl-7,8-dihy-
droxy-4-methyl-chromen-2-ones (8/9), which were then
subjected to nuclear prenylation concomitant with reductive
cyclization by using 2-methyl-3-buten-2-ol and p-toluene
sulphonic acid as a catalyst to yield 3-alkyl-10-hydroxy-
4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one
(11/12) (Scheme 1) (Kathuria et al., 2011). Alkylated b-ke-
toesters used in the reaction were synthesized according to
the well-established protocol reported from our group
(Kathuria et al., 2009). Compounds 10–12 on reaction with
3-bromoprop-1-yne using potassium carbonate as a base and
acetone as solvent gave the corresponding propargylated
derivatives (13–15) in quantitative yields (Scheme 1). A
large array of azides (16–24) were synthesized according to
the literature procedures, i.e. compounds 16–20 were syn-
thesized from their corresponding bromo derivatives by
treatment with sodium azide in DMSO as solvent
(Scheme S1, Supporting Information) (Wilkening et al.,
2011). Compounds 21 and 22 were synthesized from their
corresponding amino derivatives in two steps, i.e. first dia-
zotization reaction was carried out, followed by azidation
using sodium azide (Scheme S2, SI) (Wilkening et al., 2011).
Compound 23 was synthesized from glycerol using a bio-
catalytic approach (Scheme S3, SI) (Gupta et al., 2013).
2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl azide (24) too
was synthesized following the literature method (Scheme S4,
SI) (Salunke et al., 2011). The synthesized azides (16–24)
were then click coupled with the acetylenic pyranochromen-
2-ones (13–15) to afford the corresponding triazolyl pyra-
nochromen-2-ones (25–29, 31–34, 36–40, 42–45, 47–51,
53–56; Scheme 1). Subsequent hydrolysis/deacetylation of
compounds 29, 34, 40, 45, 51 and 56 afforded the corre-
sponding triazolyl pyranochromen-2-ones 30, 35, 41, 46, 52
and 57, respectively (Scheme 2).
Various spectroscopic techniques, e.g. IR, UV, H, 13C
and HRMS, were employed to achieve the structural
characterization of all the synthesized compounds, and the
data for known compounds were compared with the liter-
ature value.
Biology
Antibacterial activity
The antibacterial screening of all the synthesized triazolyl
pyranochromen-2-ones (25–57) was carried out against a
broad range of pathogenic microbial strains using disc
diffusion assay with some modifications (Pathak et al.,
2013; Yadav et al., 2014). Disc diffusion assay, at a con-
centration of 250 lg/disc, was performed in order to
evaluate the inhibitory potency of the compounds against
seven pathogenic bacterial strains namely Bacillus cereus,
Bacillus subtilis, Staphylococcus aureus, Pseudomonas
aeruginosa, Escherichia coli, Salmonella typhimurium and
Klebsiella pneumoniae. Out of thirty-three (25–57), six
compounds, i.e. 41, 44, 46, 52, 55 and 57, were found to
inhibit the growth of both gram-positive and gram-negative
bacteria by developing a zone of inhibition in the range of
10-16 mm (Table 1). From the activity results, it could be
observed that the incorporation of ethyl and n-hexyl chain
at C-3 position of pyranochromen-2-one along with tria-
zole ring bearing polar groups led to the observance of
antibacterial activity. However, no noticeable zone of
inhibition could be observed for the precursors (14 & 15)
of the active compounds.
To have further insights on the antibacterial action of the
active compounds 41, 44, 46, 52, 55 and 57, minimum
inhibitory concentration (MIC) was evaluated using broth
dilution assay (Pathak et al., 2013; Yadav et al., 2014). The
results demonstrated that these compounds exhibited
moderate antibacterial activity as compared to the standard
123

Med Chem Res
Scheme 1 Synthesis of triazolyl pyranocoumarin derivatives: (i) 2-
methylbuta-1,3-diene, H3PO4, xylene, 15 h, 25 °C. (ii) Ethyl
3-oxobutanoate, conc. H2SO4, 12 h, 25 °C. (iii) Ethyl 2-ethyl-3-
oxobutanoate/ethyl 2-acetyloctanoate, conc. H2SO4, 12 h, 25 °C. (iv)
2-Methyl-3-buten-2-ol, p-TSA, toluene, reflux, 24 h. (v) 3-Bromo-
prop-1-yne, K2CO3, acetone, 12 h, 25 °C. (vi) R2–N3 (16–24),
CuSO4Á5H2O, sodium ascorbate, THF:H2O (3:1), 12 h, 25 °C
drug gentamicin, with MIC values in the range of
75–170 lg/mL (Table 2).
(Fig. 3). A comparison of substituents at the C-3 position
of pyranochromen-2-one skeleton suggested that the
incorporation of alkyl chain (ethyl, n-hexyl) at the C-3
position led to an enhancement in the antibacterial activity.
The compounds lacking such substituents do not exhibit
any noticeable activity. Furthermore, it has been observed
that the coupling of polar groups (glycerol, acetic acid, D-
glucose, etc.) via the triazolyl link to the pyranochromen-2-
one moiety enhances the antimicrobial potential of result-
ing compounds and this is supported by the fact that all of
the shortlisted compounds, i.e. 41, 44, 46, 52, 55 and 57,
bear the polar groups at the triazolyl ring besides having
the alkyl substitution at C-3 position of benzopyrone ring.
However, the precursors of these triazolyl derivatives, i.e.
compounds 14 and 15, have insignificant activity, thus
suggesting that triazolyl ring favours antibacterial activity.
On comparing the antibacterial potential of triazolyl
derivatives 41, 44, 46, 52, 55 and 57, compound 55 bearing
two hydroxyl groups linked through triazole ring and n-
hexyl chain at C-3 position of pyranochromen-2-one was
found to have the lowest MIC value for most of the bac-
terial test strains. The precursors 14 and 15 of triazolyl
compounds exhibited even higher MIC values than that of
the shortlisted active compounds.
Structure activity relationship (SAR)
Out of the thirty-three triazolyl compounds (25–57)
screened, six compounds exhibited reasonable antimicro-
bial activity and efforts were also made to develop SAR
123

Med Chem Res
Scheme 2 Synthesis of
triazolyl pyranocoumarin
derivatives: (i) 1 N NaOH,
MeOH, 12 h, 25 °C. (ii)
NaOMe, MeOH, 2 h, 25 °C
Table 1 Zone of inhibition (mm) of active compounds 41, 44, 46, 52, 55, 57 and their precursors 14 and 15 against pathogenic bacterial test
strains using gentamicin as positive control
Compound
B. cereus
B. subtilis
S. aureus
E. coli
K. pneumoniae
S. typhimurium
P. aeruginosa
14
0.00
\10.00
12.67
13.67
13.67
13.67
14.00
11.00
30.33
0.00
\10.00
12.00
11.67
11.33
13.00
13.33
10.00
30.67
0.00
0.00
0.00
0.00
0.00
\10.00
11.00
11.00
11.00
12.33
13.00
10.33
28.67
0.00
0.00
0.00
0.00
15
41
13.33
13.67
14.33
13.00
14.33
11.33
30.00
11.33
11.33
10.67
12.33
13.33
10.67
29.33
11.00
11.33
11.00
12.67
13.33
10.33
30.00
11.67
14.67
13.33
13.67
15.67
10.00
29.33
44
46
52
55
57
Gentamicin
Average diameter of zone of inhibition (mm) including disc diameter of 6 mm; concentration of compound = 250 lg/disc. All the experiments
were carried out in triplicate
Out of thirty-three compounds screened (25–57), six
compounds, i.e. 41, 44, 46, 52, 55 and 57, exhibited
moderate activity against all the tested strains with zone of
inhibition between 10 and 16 mm and MIC value in the
range of 75–170 lg/mL when compared with the standard
gentamicin. Apart from these compounds, none of the
compounds in the series were found to exhibit significant
activity. The SAR observed from the activity results
demonstrated that the alkyl substituents at C-3 position of
pyranochromen-2-one together with the presence of polar
Conclusions
In summary, a total of thirty-three novel triazolyl pyra-
nochromen-2-one derivatives were synthesized and fully
characterized by 1H NMR, 13C NMR, UV, FT-IR and high-
resolution mass spectroscopy (HRMS). All of the synthe-
sized compounds were evaluated for their antibacterial
activity against both gram-positive (B. cereus, B. subtilis
and S. aureus) and gram-negative bacterial strains (P.
aeruginosa, E. coli, S. typhimurium and K. pneumoniae).
123

Med Chem Res
Table 2 Minimum inhibitory concentration (lg/mL) of active compounds 41, 44, 46, 52, 55, 57 and their precursors 14 and 15 against
pathogenic bacterial test strains using gentamicin as positive control
Compound
B. cereus
B. subtilis
S. aureus
E. coli
K. pneumoniae
S. typhimurium
P. aeruginosa
14
200.00
200.00
127.67
127.67
127.67
127.67
110.00
127.67
0.26
187.67
200.00
155.00
127.67
160.00
155.00
105.00
155.00
0.10
187.67
187.67
127.67
100.00
127.67
127.67
75.00
150.00
200.00
126.67
126.67
126.67
126.67
140.00
126.67
1.38
146.67
143.33
120.00
120.00
120.00
123.33
116.67
120.00
1.38
150.00
200.00
123.33
123.33
120.00
123.33
131.67
123.33
0.48
250.00
250.00
170.00
155.00
170.00
170.00
123.33
170.00
1.25
15
41
44
46
52
55
57
127.67
2.00
Gentamicin
All the experiments were carried out in triplicate and the results expressed as average values
Fig. 3 SAR representation in
the triazoly pyranocoumarin
derivatives
groups linked via triazolyl moiety has a tendency to pro-
mote the antibacterial activity of compounds.
were recorded on a Perkin-Elmer 2000 FT-IR spec-
1
trophotometer. The H and 13C NMR spectra were recor-
Though a moderate antibacterial potential was observed
for the compounds synthesized and screened, but the
information provided herein may be used for the design
and synthesis of newer pharmacophores with improved
antibacterial efficacy.
ded on JEOL ECX-400P (400, 100.5 MHz) NMR
spectrometer using tetramethylsilane as internal standard.
The chemical shift values are on a d scale and the coupling
constant values (J) are in Hertz. The UV data were
recorded on Cary 300 UV–Vis spectrophotometer, Agilent
Technologies. The HRMS data were recorded on Q-TOF
LCMS, Agilent Technology-6530.
Experimental section
Chemistry
General procedure for the synthesis of propargyloxy
derivatives of pyranochromen-2-ones (13–15)
Materials and methods
To a stirred solution of 10-hydroxy-4,8,8-trimethyl-7,8-
dihydropyrano[3,2-g]chromen-2(6H)- one (10)/3-ethyl-10-
hydroxy-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (11)/3-hexyl-10-hydroxy-4,8,8-trimethyl-7,8-di-
hydropyrano[3,2-g]chromen-2(6H)-one (12) (1 equiv.) and
anhydrous K2CO3 (1.5 equiv.) in acetone, 3-bromoprop-1-
yne (1.2 equiv.) was added dropwise with constant stirring
at room temperature (25 °C) for 12 h. The progress of the
reaction was monitored by TLC (MeOH:CHCl3::1:49). On
completion of the reaction, ice cold water was added to the
reaction mixture and the solid product so obtained was
The organic solvents were dried and distilled prior to their
use. Reactions were monitored by precoated TLC plates
(Merck silica gel 60F254); the spots were visualized by UV
light and ceric ammonium molybdate stain. Silica gel
(100–200 mesh) was used for column chromatography. All
of the chemicals and reagents were procured from Spec-
trochem Pvt. Ltd., India, and Sigma-Aldrich Chemicals
Pvt. Ltd., USA. Melting points were measured on a Buchi
M-560 equipment and are uncorrected. Infrared spectra
123

Med Chem Res
H-500) 1.40 (s, 6H, 29 C-8 CH3), 1.45-1.53 (m, 2H, H-200),
1.84 (t, 2H, J = 6.9 Hz, H-7), 2.34 (s, 3H, C-4 CH3), 2.37
(t, 1H, J = 2.2 Hz, H-30), 2.60 (t, 2H, J = 8.0 Hz, H-100),
2.85 (t, 2H, J = 6.9 Hz, H-6), 4.85 (d, 2H, J = 2.2 Hz,
H-10), 7.06 (1H, s, H-5); 13C (100.5 MHz, CDCl3): d 14.1
(C-600), 14.9 (C-4 CH3), 22.4 & 22.6 (C-500 & C-6), 26.8
(29 C-8 CH3), 27.6, 28.8, 29.3, 31.7 (C-100–C-400), 32.5 (C-
7), 60.0 (C-10), 75.2 (C-30), 75.8 (C-20), 79.2 (C-8), 113.9,
117.9, 119.5, 123.8, 132.5, 145.0, 145.8 & 149.5 (C-3–C-5
& C-10–C-14), 161.5 (C-2); HRMS (ESI) m/z [M ? H]?
Calculated for C24H30O4: 383.2178; found: 383.2213.
filtered. The resulting crude product was washed succes-
sively with hexane 3–4 times, and the pure compound was
collected as a light yellow solid in 85–92 % isolated yield.
4,8,8-Trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano
[3,2-g]chromen-2(6H)-one (13) The reaction of 10-hy-
droxy-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (10) (5 g, 19.21 mmol) with 3-bromoprop-1-
yne (1.99 ml, 23.05 mmol) gave the title compound 13 as a
light yellow solid (5.16 g, 90 %) by following the general
procedure; mp 184–185 °C. Rf (MeOH:CHCl3::1:49) 0.60;
m
max (KBr)/cm-1 2933, 2119, 1712, 1610; kmax (MeOH)/nm
1
329; H (400 MHz, CDCl3): d 1.41 (s, 6H, 29 C-8 CH3),
1.86 (t, 2H, J = 6.9 Hz, H-7), 2.36 (s, 3H, C-4 CH3), 2.37
(t, 1H, J = 2.2 Hz, H-30), 2.85 (t, 2H, J = 6.9 Hz, H-6),
4.85 (d, 2H, J = 2.2 Hz, H-10), 6.10 (s, 1H, H-3), 7.07 (s,
1H, H-5); 13C (100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 22.3
(C-6), 26.8 (29 C-8 CH3), 32.3 (C-7), 60.0 (C-10), 75.3 (C-
30), 76.1 (C-20), 79.0 (C-8), 111.9, 113.1, 118.3, 119.7, 132.7,
146.4, 150.8 & 152.5 (C-3–C-5 & C-10–C-14), 160.8 (C-2);
HRMS (ESI) m/z [M ? H]? Calculated for Cl8H18O4:
299.1239; found: 299.1279.
General procedure for the synthesis of triazolyl
pyranocoumarin derivatives (25–57)
In order to obtain the desired triazolyl derivatives on
pyranocoumarin scaffold, ‘‘Click chemistry’’ approach was
used, wherein the acetylenic pyranocoumarin (13–15) (l g)
taken in a round bottom flask, was dissolved in THF. The
azide (16–24) (1.2 equiv.) was then added to the reaction
mixture and stirred. To the resultant mixture so obtained,
an aqueous solution of CuSO4Á5H2O (0.2 equiv.) and
sodium ascorbate (0.4 equiv.) was added and the reaction
mixture stirred at room temperature (25 °C) for 12 h. The
progress of the reaction was monitored by TLC
(MeOH:CHCl3 in 1:49). After completion of the reaction,
the solvent was evaporated under reduced pressure. The
residue so obtained was dissolved in a saturated solution of
EDTA in distilled water and extracted with ethyl acetate
(3 9 100 mL). The organic layer was then dried over
anhydrous sodium sulphate and the solvent evaporated
under reduced pressure in a rotary evaporator. The result-
ing crude product was then subjected to column chro-
matography over silica gel 100–200 mesh size (MeOH:
CHCl3::1:20) to yield the corresponding triazolyl deriva-
tive of pyranochromen-2-one (25–29, 31–34, 36–40, 42–
45, 47–51, 53–56) in 50–78 % isolated yield. Subsequent
hydrolysis/deacetylation of compounds 29, 34, 40, 45, 51,
56 afforded the corresponding triazolyl pyranochromen-2-
ones 30, 35, 41, 46, 52, 57 in 67–90 % yield.
3-Ethyl-4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihy-
dropyrano[3,2-g]chromen-2(6H)-one (14) The reaction
of 3-ethyl-10-hydroxy-4,8,8-trimethyl-7,8- dihydropyrano
[3,2-g]chromen-2(6H)-one (11) (5 g, 17.34 mmol) with
3-bromoprop-1-yne (1.79 ml, 20.81 mmol) gave the title
compound 14 as a light yellow solid (5.09 g, 92 %) by
following the general procedure; mp 95–96 °C; Rf
(MeOH:CHCl3::1:49) 0.62; mmax (KBr)/cm-1 2965, 2117,
1692, 1618; kmax (MeOH)/nm 329. 1H (400 MHz, CDCl3):
d 1.11 (t, 3H, J = 8.0 Hz, H-200) 1.40 (s, 6H, 29 C-8 CH3),
1.84 (t, 2H, J = 6.9 Hz, H-7), 2.34 (s, 3H, C-4 CH3), 2.37
(t, 1H, J = 2.2 Hz, H-30), 2.64 (q, 2H, J = 8.0 Hz, H-100),
2.84 (t, 2H, J = 6.9 Hz, H-6), 4.85 (d, 2H, J = 2.2 Hz,
H-10), 7.06 (s, 1H, H-5); 13C (100.5 MHz, CDCl3): d 13.2
(C-200), 14.6 (C-4 CH3), 20.8 (C-100), 22.4 (C-6), 26.8 (29
C-8 CH3), 32.5 (C-7), 60.0 (C-10), 75.2 (C-30), 75.8 (C-20),
79.2 (C-8), 113.8, 118.0, 119.5, 124.9, 132.5, 145.0, 145.6
& 149.6 (C-3–C-5 & C-10–C-14), 161.4 (C-2); HRMS
(ESI) m/z [M ? H]? Calculated for C20H22O4: 327.1552;
found: 327.1588.
10-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-4,8,8-trimethyl-
7,8-dihydropyrano[3,2-g] chromen-2(6H)-one (25) The
reaction of 4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-di-
hydropyrano[3,2-g]chromen- 2(6H)-one (13) (1 g, 3.35
mmol) with (azidomethyl)benzene (16) (0.54 g, 4.02
mmol) gave the title compound 25 as a greenish solid
(0.94 g, 65 %) by following the general procedure; mp
121–122 °C; Rf (MeOH:CHCl3::1:49) 0.31; mmax (KBr)/
cm-1 2975, 2924, 1718 (C=O), 1608, 1567; kmax (MeOH)/
3-Hexyl-4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihy-
dropyrano[3,2-g]chromen-2(6H)-one (15) The reaction
of 3-hexyl-10-hydroxy-4,8,8-trimethyl-7,8- dihydropyrano
[3,2-g]chromen-2(6H)-one (12) (5 g, 14.52 mmol) with
3-bromoprop-1-yne (1.50 ml, 17.42 mmol) gave the title
compound 15 as a light yellow solid (4.99 g, 85 %) by
following the general procedure; mp 84–85 °C; Rf
(MeOH:CHCl3::1:49) 0.63; mmax (KBr)/cm-1 2928, 2122,
1713, 1613; kmax (MeOH)/nm 329; 1H (400 MHz, CDCl3):
d 0.87 (t, 3H, J = 7.3 Hz, H-600), 1.27-1.36 (m, 6H, H-300–
1
nm 329; H (400 MHz, CDCl3): d 1.36 (s, 6H, 29 C-8
CH3), 1.82 (t, 2H, J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4 CH3),
2.81 (t, 2H, J = 6.5 Hz, H-6), 5.27 (s, 2H, H-1a), 5.52 (s,
123

Med Chem Res
2H, H-4a), 6.03 (s, 1H, H-3), 7.02 (s, 1H, H-5), 7.28–7.38
(m, 5H, H-200–H-600), 8.02 (s, 1H, H-50); 13C (100.5 MHz,
CDCl3): d 18.7 (C-4 CH3), 22.2 (C-6), 26.8 (29 C-8 CH3),
32.2 (C-7), 54.3 (C-1a), 66.8 (C-4a), 76.1 (C-8), 128.2 (C-
200 & C-600), 129.0 (C-300 & C-500), 111.7, 113.0, 118.4,
119.5, 128.6, 133.7, 134.4, 146.0, 150.6 & 152.6 (C-3–C-5,
C-10–C-14, C-40, C-50, C-100 & C-400), 160.7 (C-2); HRMS
(ESI) m/z [M ? H]? Calculated for C25H25N3O4:
432.1879; found: 432.1918.
C-400), 160.8 (C-2); HRMS (ESI) m/z [M ? H]? Calculated
for C25H24N4O6: 477.1729; found: 477.1765.
10-[(1-Hexyl-1H-1,2,3-triazol-4-yl)methoxy]-4,8,8-trimethyl-
7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (28) The
reaction of 4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-di-
hydropyrano[3,2-g]chromen- 2(6H)-one (13) (1 g, 3.35
mmol) with 1-azidohexane (19) (0.51 g, 4.02 mmol) gave
the title compound 28 as a reddish brown solid (1.03 g,
72 %) by following the general procedure; mp 88–89 °C;
Rf (MeOH:CHCl3::1:49) 0.32; mmax (KBr)/cm-1 2956,
10-[(1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy]-
4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (26) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-
1-yloxy)-7,8-dihydropyrano[3,2-g]chromen- 2(6H)-one (13)
(1 g, 3.35 mmol) with 1-(azidomethyl)-4-fluorobenzene
(17) (0.61 g, 4.02 mmol) gave the title compound 26 as a
brown solid (1.06 g, 70 %) by following the general pro-
cedure; mp 147–148 °C; Rf (MeOH:CHCl3::1:49) 0.32; mmax
(KBr)/cm-1 2980, 2944, 1714 (C=O), 1608, 1566; kmax
(MeOH)/nm 330; 1H (400 MHz, CDCl3): d 1.37 (s, 6H, 29
C-8 CH3), 1.83 (t, 2H, J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4
CH3), 2.82 (t, 2H, J = 6.5 Hz, H-6), 5.27 (s, 2H, H-1a), 5.47
(s, 2H, H-4a), 6.03 (s, 1H, H-3), 7.01–7.03 (m, 2H, H-200 &
H-600), 7.05 (s, 1H, H-5), 7.26–7.30 (m, 2H, H-300 & H-500),
7.95 (s, 1H, H-50); 13C (100.5 MHz, CDCl3): d 18.7 (C-4
CH3), 22.3 (C-6), 26.8 (29 C-8 CH3), 32.3 (C-7), 53.4 (C-
1a), 67.0 (C-4a), 76.1 (C-8), 116.0 (d, J = 22.0 Hz, C-300 &
C-500), 130.1 (d, J = 8.6 Hz, C-200 & C-600), 130.6 (d,
J = 2.8 Hz, C-100), 111.7, 113.0, 118.5, 119.5, 123.6, 133.8,
145.4, 146.0, 150.7 & 152.6 (C-3–C-5, C-10–C-14, C-40 &
C-50), 160.8 (C-2), 162.8 (d, J = 247.2 Hz, C-400); HRMS
(ESI) m/z [M ? H]? Calculated for C25H24FN3O4:
450.1784; found: 450.1824.
1
2933, 1716 (C=O), 1617, 1569; kmax (MeOH)/nm 330; H
(400 MHz, CDCl3): d 0.86 (t, 3H, J = 7.3 Hz, H-600),
1.24–129 (m, 6H, H-300–H-500), 1.40 (s, 6H, 29 C-8 CH3),
1.85 (t, 2H, J = 6.5 Hz, H-7), 1.87–1.93 (m, 2H, H-200)
2.33 (s, 3H, C-4 CH3), 2.83 (t, 2H, J = 6.5 Hz, H-6), 4.34
(t, 2H, J = 7.3 Hz, H-100), 5.30 (s, 2H, H-4a), 6.04 (s, 1H,
H-3), 7.03 (s, 1H, H-5), 8.05 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.9 (C-600), 18.7 (C-4 CH3), 22.2
& 22.3 (C-500 & C-6), 26.8 (29 C-8 CH3), 26.1, 30.1 &
31.1 (C-200–C-400), 32.3 (C-7), 50.6 (C-100), 66.9 (C-4a),
76.2 (C-8), 111.7, 113.0, 118.5, 119.6, 133.8, 146.0, 150.7
& 152.7 (C-3–C-5, C-10–C-14, C-40 & C-50), 160.9 (C-2);
HRMS (ESI) m/z [M ? H]? Calculated for C24H31N3O4:
426.2348; found: 426.2386
Ethyl 2-[4-(((2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropy-
rano[3,2-g]chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-
yl]acetate (29) The reaction of 4,8,8-trimethyl-10-(prop-
2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]chromen- 2(6H)-
one (13) (1 g, 3.35 mmol) with ethyl 2-azidoacetate (20)
(0.52 g, 4.02 mmol) gave the title compound 29 as a red-
dish brown solid (1.05 g, 73 %) by following the general
procedure; mp 137–138 °C; Rf (MeOH:CHCl3::1:49) 0.34;
mmax (KBr)/cm-1 2929, 1747 (C=O), 1717 (C=O), 1569;
4,8,8-Trimethyl-10-[(1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-
yl)methoxy]-7,8-dihydropyrano[3,2-g] chromen-2(6H)-one
(27) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-1-
yloxy)-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (13)
(1 g, 3.35 mmol) with 1-(azidomethyl)-4-nitrobenzene
(18) (0.72 g, 4.02 mmol) gave the title compound 27 as a
dark yellow solid (1.09 g, 68 %) by following the general
procedure; mp 157–158 °C; Rf (MeOH:CHCl3::1:49) 0.32;
mmax (KBr)/cm-1 2981, 2945, 1712 (C=O), 1610, 1524,
1397, 1340; kmax (MeOH)/nm 330; 1H (400 MHz, CDCl3):
d 1.40 (s, 6H, 29 C-8 CH3), 1.85 (t, 2H, J = 6.5 Hz, H-7),
2.33 (s, 3H, C-4 CH3), 2.84 (t, 2H, J = 6.5 Hz, H-6), 5.30
(s, 2H, H-4a), 5.63 (s, 2H, H-1a), 6.00 (s, 1H, H-3), 7.03 (s,
1H, H-5), 7.41 (d, 2H, J = 8.8 Hz, H-200 & H-600), 8.09 (s,
1H, H-50) 8.19 (d, 2H, J = 8.8 Hz, H-300 & H-500); 13C
(100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 22.3 (C-6), 26.9
(29 C-8 CH3), 32.3 (C-7), 53.1 (C-1a), 70.0 (C-4a), 75.8
(C-8), 124.2 (C-200, C-600 & C-50), 128.7 (C-300 & C-500),
111.6, 113.0, 118.6, 119.6, 133.8, 141.7, 145.9, 146.0,
147.9, 150.7 & 152.8 (C-3–C-5, C-10–C-14, C-40, C-100 &
1
kmax (MeOH)/nm 329; H (400 MHz, CDCl3): d 1.28 (t,
3H, J = 7.3 Hz, H-20000), 1.40 (s, 6H, 29 C-8 CH3), 1.85 (t,
2H, J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4 CH3), 2.83 (t, 2H,
J = 6.5 Hz, H-6), 4.25 (q, 2H, J = 7.3 Hz, H-10000), 5.16 (s,
2H, H-100), 5.33 (s, 2H, H-4a), 6.03 (s, 1H, H-3), 7.03 (s,
1H, H-5), 8.18 (s, 1H, H-50); 13C (100.5 MHz, CDCl3): d
14.0 (C-20000), 18.7 (C-4 CH3), 22.2 (C-6), 26.8 (29 C-8
CH3), 32.3 (C-7), 51.0 (C-100), 62.3 (C-10000), 66.8 (C-4a),
75.9 (C-8), 111.7, 113.0, 118.5, 119.6, 133.8, 146.0, 150.7
& 152.7 (C-3–C-5, C-10–C-14, C-40 & C-50), 160.9 (C-2),
166.1 (C-200); HRMS (ESI) m/z [M ? H]? Calculated for
C22H25N3O6: 428.1777; found: 428.1817.
2-[4-(((2,2,6-Trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]
chromen-10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]acetic acid
(30) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-1-
yloxy)-7,8-dihydropyrano[3,2-g]chromen- 2(6H)-one (13)
(1 g, 3.35 mmol) with ethyl 2-azidoacetate (20) (0.52 g,
4.02 mmol) followed by hydrolysis gave the title
123

Med Chem Res
compound 30 as a red solid (0.84 g, 86 %) by following the
general procedure; mp 235–236 °C; Rf (MeOH:CHCl3::
1:19) 0.30; mmax (KBr)/cm-1 3432, 2945, 1742 (C=O),
J = 8.7 Hz, H-200 & H-600), 8.43 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 22.3 (C-6), 26.9
(29 C-8 CH3), 32.3 (C-7), 55.6 (OCH3), 67.2 (C-4a), 76.1
(C-8), 114.7 (C-300 & C-500), 122.1 (C-200 & C-600), 111.8,
113.1, 118.5, 119.6, 130.6, 134.0, 145.5, 146.1, 150.8 &
152.8 (C-3–C-5, C-10–C-14, C-40, C-50 & C-100), 159.7 (C-
400), 161.0 (C-2); HRMS (ESI) m/z [M ? H]? Calculated
for C25H25N3O5: 448.1867; found: 448.1851.
1
1714 (C=O), 1618; kmax (MeOH)/nm 329; H (400 MHz,
DMSO-d6): d 1.31 (s, 6H, 29 C-8 CH3), 1.79 (t, 2H,
J = 6.5 Hz, H-7), 2.34 (s, 3H, C-4 CH3), 2.80 (t, 2H,
J = 6.5 Hz, H-6), 5.12 (s, 2H, H-100), 5.25 (s, 2H, H-4a),
6.15 (s, 1H, H-3), 7.26 (s, 1H, H-5), 8.12 (s, 1H, H-50),
13.36 (brs, 1H, COOH); 13C (100.5 MHz, DMSO-d6): d
18.2 (C-4 CH3), 21.6 (C-6), 26.5 (29 C-8 CH3), 31.6 (C-7),
50.5 (C-100), 65.4 (C-4a), 76.0 (C-8), 111.1, 112.6, 118.6,
120.1, 126.0, 132.8, 143.0, 145.7, 150.2 & 153.4 (C-3–C-5,
C-10–C-14, C-40 & C-50), 159.8 (C-2), 168.6 (C-200);
HRMS (ESI) m/z [M ? H]? Calculated for C20H21N3O6:
400.1503; found: 400.1501.
10-[(1-(1,3-Dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)
methoxy]-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (33) The reaction of 4,8,8-trimethyl-10-(prop-
2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]chromen- 2(6H)-
one (13) (1 g, 3.35 mmol) with 2-azidopropane-1,3-diol
(23) (0.47 g, 4.02 mmol) gave the title compound 33 as
an off-white solid (1.09 g, 78 %) by following the general
procedure; mp 124–125 °C; Rf (MeOH:CHCl3::1:19)
0.32; mmax (KBr)/cm-1 3434, 2971, 1717 (C=O), 1618,
10-[(1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy]-
4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (31) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-
1-yloxy)-7,8-dihydropyrano[3,2-g]chromen- 2(6H)-one (13)
(1 g, 3.35 mmol) with 1-azido-3-fluorobenzene (21) (0.55 g,
4.02 mmol) gave the title compound 31 as a brown solid
(0.88 g, 60 %) by following the general procedure; mp
155–156 °C; Rf (MeOH:CHCl3::1:49) 0.33; mmax (KBr)/
cm-1 2928, 1713 (C=O), 1612, 1570; kmax (MeOH)/nm 330;
1H (400 MHz, CDCl3): d 1.41 (s, 6H, 29 C-8 CH3), 1.86 (t,
2H, J = 6.5 Hz, H-7), 2.35 (s, 3H, C-4 CH3), 2.85 (t, 2H,
J = 6.5 Hz, H-6), 5.37 (s, 2H, H-4a), 060 .08 (s, 1H, H-3), 7.06
(s, 1H, H-5), 7.10-7.15 (m, 1H, H-2 ), 7.47–7.52 (m, 1H,
H-400), 7.59–7.65 (m, 2H, H-500 & H-600), 8.57 (s, 1H, H-50);
13C (100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 22.3 (C-6),
26.9 (29 C-8 CH3), 32.4 (C-7), 67.3 (C-4a), 76.2 (C-8),
108.3 (d, J = 25.8 Hz, C-200), 115.5 (d, J = 21.0 Hz, C-400),
115.8 (d, J = 2.8 Hz, C-600), 131.2 (d, J = 9.5 Hz, C-100),
138.3 (d, J = 10.5 Hz, C-500), 111.8, 113.2, 118.6, 119.7,
121.9, 134.1, 146.1, 146.2, 150.7 & 152.7 (C-3–C-5, C-10–
C-14, C-40 & C-50), 160.9 (C-2), 163.1 (d, J = 248.2 Hz,
C-300); HRMS (ESI) m/z [M ? H]? Calculated for C24H22
FN3O4: 436.1667; found: 436.1672.
1
1570; kmax (MeOH)/nm 329; H (400 MHz, CDCl3): d
1.46 (s, 6H, 29 C-8 CH3), 1.90 (t, 2H, J = 6.9 Hz, H-7),
2.33 (s, 3H, C-4 CH3), 2.87 (t, 2H, J = 6.9 Hz, H-6), 3.71
(brs, 2H, OH), 4.06–4.16 (m, 4H, H-100 & H-300),
4.62–4.66 (m, 1H, H-200) 5.23 (s, 2H, H-4a), 5.98 (s, 1H,
H-3), 7.07 (s, 1H, H-5), 8.33 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 22.3 (C-6), 27.0
(29 C-8 CH3), 32.3 (C-7), 62.6 (C-100 & C-300), 64.1 (C-
200), 66.7 (C-4a), 76.3 (C-8), 111.3, 113.1, 119.0, 119.9,
125.2, 133.9, 144.3, 146.2, 151.0 & 153.7 (C-3–C-5,
C-10–C-14, C-40 & C-50), 162.0 (C-2); HRMS (ESI) m/z
[M ? H]? Calculated for C21H25N3O6: 416.1816; found:
416.1819.
(2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-[4-(((2,2,6-trimethyl-
8-oxo-2,3,4,8-tetrahydropyrano [3,2-g]chromen-10-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl]tetrahydro-2H-pyran-3,4,5-
triyl triacetate (34) The reaction of 4,8,8-trimethyl-10-
(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (13) (1 g, 3.35 mmol) with 2,3,4,6-tetra-
O-acetyl-b-D-glucopyranosyl azide (24) (1.50 g, 4.02
mmol) gave the title compound 34 as a white solid
(1.35 g, 60 %) by following the general procedure; mp
148–149 °C; Rf (MeOH:CHCl3::1:49) 0.34; mmax (KBr)/
cm-1 2952, 1761 (C=O), 1718 (C=O), 1617; kmax
10-[(1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy]-
4,8,8-trimethyl-7,8-dihydropyrano [3,2-g]chromen-2(6H)-
one (32) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-
1-yloxy)-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (13)
(1 g, 3.35 mmol) with 1-azido-4-methoxybenzene (22)
(0.60 g, 4.02 mmol) gave the title compound 32 as a
greenish solid (0.98 g, 65 %) by following the general
procedure; mp 168–169 °C; Rf (MeOH:CHCl3::1:49) 0.30;
mmax (KBr)/cm-1 2937, 1708 (C=O), 1610, 1519; kmax
(MeOH)/nm 329; 1H (400 MHz, CDCl3): d 1.40 (s, 6H, 29
C-8 CH3), 1.85 (t, 2H, J = 6.5 Hz, H-7), 2.35 (s, 3H, C-4
CH3), 2.84 (t, 2H, J = 6.5 Hz, H-6), 3.86 (s, 3H, OCH3)
5.37 (s, 2H, H-4a), 6.08 (s, 1H, H-3), 7.02 (d, 2H,
J = 8.7 Hz, H-300 & H-500), 7.05 (s, 1H, H-5), 7.70 (d, 2H,
1
(MeOH)/nm 331; H (400 MHz, CDCl3): d 1.37 (s, 3H,
C-8 CH3), 1.38 (s, 3H, C-8 CH3) 1.81 (t, 2H,
J = 7.3 Hz, H-7), 1.85 (s, 3H, COCH3), 2.02 (s, 3H,
COCH3), 2.06 (s, 3H, COCH3), 2.09 (s, 3H, COCH3),
2.34 (s, 3H, C-4 CH3), 2.82 (t, 2H, J = 7.3 Hz, H-6),
3.98 (ddd, 1H, J = 2.2 Hz, 5.1 Hz & 10.2 Hz, H-500),
4.14 (dd, 1H, J = 2.2 Hz & 12.4 Hz, H-600a/H-600b),
4.27 (dd, 1H, J = 5.1 Hz & 12.4 Hz, H-600a/H-600b),
5.23–5.28 (m, 1H, H-400), 5.30 (d, 2H, J = 5.1 Hz,
H-4a), 5.40 (t, 1H, J = 9.5 Hz, H-300), 5.53 (t, 1H,
J = 9.5 Hz, H-200), 5.85 (d, 1H, J = 9.5 Hz, H-100), 6.07
123

Med Chem Res
(s, 1H, H-3), 7.04 (s, 1H, H-5), 8.18 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 18.7 (C-4 CH3), 20.1 (COCH3),
20.2 (COCH3), 20.5 (COCH3), 20.7 (COCH3), 22.2 (C-
6), 26.7 (C-8 CH3), 26.8 (C-8 CH3), 32.3 (C-7), 61.6 (C-
600), 67.7 (C-4a), 70.2, 72.8, 74.9 & 74.8 (C-200–C-500),
76.0 (C-8), 85.6 (C-100), 112.0, 113.1, 118.4, 119.6,
122.5, 133.8, 145.5, 146.0, 150.5 & 152.5 (C-3–C-5,
C-10–C-14, C-40 & C-50), 160.8 (C-2), 168.7 (COCH3),
169.3 (COCH3), 170.0 (COCH3), 170.6 (COCH3);
HRMS (ESI) m/z [M ? H]? Calculated for
C32H37N3O13: 672.2360; found: 672.2388.
2H, H-1a), 5.52 (s, 2H, H-4a), 7.02 (s, 1H, H-5), 7.28–7.35
(m, 5H, H-200–H-600), 8.03 (s, 1H, H-50); 13C (100.5 MHz,
CDCl3): d 13.1 (C-2¢¢¢), 14.5 (C-4 CH3), 20.8 (C-1¢¢¢), 22.3
(C-6), 26.8 (29 C-8 CH3), 32.3 (C-7), 54.3 (C-1a), 67.0 (C-
4a), 75.7 (C-8), 128.1 (C-200 & C-600), 129.0 (C-300 & C-500),
113.8, 118.1, 119.3, 124.6, 128.6, 133.5, 134.5, 144.5,
145.7 & 149.4 (C-3–C-5, C-10–C-14, C-40, C-50, C-100 &
C-400), 161.3 (C-2); HRMS (ESI) m/z [M ? H]? Calculated
for C27H29N3O4: 460.2192; found: 460.2229.
3-Ethyl-10-[(1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)me-
thoxy]-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (37) The reaction of 3-ethyl-4,8,8-trimethyl-
4,8,8-Trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-
6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-1H-1,2,3-tria-
zol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (35) The reaction of 4,8,8-trimethyl-10-(prop-2-yn-1-
yloxy)-7,8-dihydropyrano[3,2-g]chromen-2(6H)-one (13)
(1 g, 3.35 mmol) with 2,3,4,6-tetra-O-acetyl-b-D-glu-
copyranosyl azide (24) (1.50 g, 4.02 mmol) followed by
subsequent deacetylation gave the title compound 35 as a
brown solid (1.51 g, 67 %) by following the general pro-
cedure; mp 120–121 °C; Rf (MeOH:CHCl3::1:9) 0.30; mmax
(KBr)/cm-1 3402, 2974, 2924, 1709 (C=O), 1609, 1566;
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chro-
men-2(6H)-one (14) (1 g, 3.06 mmol) with 1-(azido-
methyl)-4-fluorobenzene (17) (0.55 g, 3.67 mmol) gave the
title compound 37 as a yellow solid (0.95 g, 65 %) by
following the general procedure; mp 139–140 °C; Rf
(MeOH:CHCl3::1:49) 0.35. mmax (KBr)/cm-1 2971, 2943,
1706 (C=O), 1610, 1571; kmax (MeOH)/nm 329; 1H
(400 MHz, CDCl3): d 1.10 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.36
(s, 6H, 29 C-8 CH3), 1.82 (t, 2H, J = 6.5 Hz, H-7), 2.32
(s, 3H, C-4 CH3), 2.61 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.82 (t,
2H, J = 6.5 Hz, H-6), 5.28 (s, 2H, H-1a), 5.49 (s, 2H,
H-4a), 7.01–7.06 (m, 3H, H-200, H-600 & H-5), 7.27–7.31
(m, 2H, H-300 & H- 500), 8.04 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.1 (C-2¢¢¢), 14.5 (C-4 CH3), 20.7
(C-1¢¢¢), 22.3 (C-6), 26.8 (29 C-8 CH3), 32.4 (C-7), 53.5
(C-1a), 67.0 (C-4a), 75.8 (C-8), 115.8 (d, J = 22.0 Hz,
C-300 & C-500), 130.1 (d, J = 8.6 Hz, C-200 & C-600), 130.4
(d, J = 3.8 Hz, C-100), 113.8, 118.2, 119.4, 124.6, 133.5,
144.5, 145.8 & 149.4 (C-3–C-5, C-10–C-14, C-40 & C-50),
161.4 (C-2), 162.7 (d, J = 248.2 Hz, C-400); HRMS (ESI)
m/z [M ? H]? Calculated for C27H28FN3O4: 478.2097;
found: 478.2136.
1
kmax (MeOH)/nm 331; H (400 MHz, DMSO-d6): d 1.29
(s, 6H, 29 C-8 CH3), 1.76 (t, 2H, J = 6.4 Hz, H-7), 2.32
(s, 3H, C-4 CH3), 2.77 (t, 2H, J = 6.4 Hz, H-6), 3.17–3.23
(m, 1H, H-200), 3.35–3.44 (m, 3H, H-300, H-400 & H-600a/H-
600b), 3.65 (dd, 1H, J = 5.5 Hz & 10.0 Hz, H-600a/H-600b),
3.67–3.76 (m, 1H, H-500) 4.58 (t, 1H, J = 5.9 Hz, OH),
5.08 (s, 2H, H-4a), 5.15 (d, 1H, J = 5.0 Hz, OH), 5.27 (d,
1H, J = 4.5 Hz, OH), 5.34 (d, 1H, J = 5.9 Hz, OH), 5.51
(d, 1H, J = 9.1 Hz, H-100), 6.13 (s, 1H, H-3), 7.24 (s, 1H,
H-5), 8.31 (s, 1H, H-50); 13C (100.5 MHz, DMSO-d6): d
18.8 (C-4 CH3), 22.1 (C-6), 27.1 (29 C-8 CH3), 32.1 (C-7),
61.3 (C-600), 66.2 (C-4a), 70.1, 72.7, 76.6, 77.5 & 80.5 (C-8
& C-200–C-500), 88.0 (C-100), 111.6, 113.2, 119.2, 120.7,
124.3, 133.6, 143.6, 146.1, 150.7 & 154.1 (C-3–C-5, C-10–
C-14, C-40 & C-50), 160.4 (C-2); HRMS (ESI) m/z
[M ? H]? Calculated for C24H29N3O9: 504.1977; found:
504.1998.
3-Ethyl-4,8,8-trimethyl-10-[(1-(4-nitrobenzyl)-1H-1,2,3-tri-
azol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (38) The reaction of 3-ethyl-4,8,8-trimethyl-10-
(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (14) (1 g, 3.06 mmol) with 1-(azidomethyl)-4-
nitrobenzene (18) (0.65 g, mmol) gave the title compound
38 as a yellow solid (1.05 g, 68 %) by following the gen-
eral procedure; mp 196–197 °C; Rf (MeOH:CHCl3::1:49)
0.33; mmax (KBr)/cm-1 2980, 2934, 1702 (C=O), 1609,
10-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-3-ethyl-4,8,8-
trimethyl-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one
(36) The reaction of 3-ethyl-4,8,8-trimethyl-10-(prop-2-
yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-2(6H)-one
(14) (1 g, 3.06 mmol) with (azidomethyl)benzene (16)
(0.49 g, 3.67 mmol) gave the title compound 36 as a light
yellow solid (0.92 g, 65 %) by following the general pro-
cedure; mp 155–156 °C; Rf (MeOH:CHCl3::1:49) 0.32;
mmax (KBr)/cm-1 2964, 2934, 1708 (C=O), 1611, 1570;
1
1570, 1366, 1347; kmax (MeOH)/nm 330; H (400 MHz,
CDCl3): d 1.08 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.39 (s, 6H, 29
C-8 CH3), 1.85 (t, 2H, J = 6.5 Hz, H-7), 2.32 (s, 3H, C-4
CH3), 2.59 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.83 (t, 2H,
J = 6.5 Hz, H-6), 5.30 (s, 2H, H-1a), 5.64 (s, 2H, H-4a),
7.04 (s, 1H, H-5), 7.41 (d, 2H, J = 8.8 Hz, H-200 & H- 600),
8.17 (s, 1H, H-50), 8.19 (d, 2H, J = 8.8 Hz, H-300 & H-500);
13C (100.5 MHz, CDCl3): d 13.1 (C-2¢¢¢), 14.5 (C-4 CH3),
20.7 (C-1¢¢¢), 22.3 (C-6), 26.8 (29 C-8 CH3), 32.4 (C-7),
1
kmax (MeOH)/nm 330; H (400 MHz, CDCl3): d 1.10 (t,
3H, J = 7.3 Hz, H-2¢¢¢), 1.34 (s, 6H, 29 C-8 CH3), 1.81 (t,
2H, J = 6.5 Hz, H-7), 2.32 (s, 3H, C-4 CH3), 2.62 (q, 2H,
J = 7.3 Hz, H-1¢¢¢), 2.81 (t, 2H, J = 6.5 Hz, H-6), 5.28 (s,
123

Med Chem Res
53.2 (C-1a), 67.1 (C-4a), 75.7 (C-8), 124.2 (C-200 & C-600),
128.7 (C-300 & C-500), 113.8, 118.3, 119.5, 124.4, 124.6,
133.5, 141.7, 144.4, 145.9, 146.0, 147.9 & 149.4 (C-3–C-5,
C-10–C-14, C-40, C-50, C-100 & C-400), 161.4 (C-2); HRMS
(ESI) m/z [M ? H]? Calculated for C27H28N4O6:
505.2042; found: 505.2082.
145.8 & 149.5 (C-3–C-5, C-10–C-14, C-40 & C-50), 161.5
(C-2), 166.2 (C-200); HRMS (ESI) m/z [M ? H]? Calcu-
lated for C24H29N3O6: 456.2090; found: 456.2128.
2-[4-(((7-Ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropy-
rano[3,2-g]chromen-10-yl)oxy) methyl)-1H-1,2,3-triazol-l-
yl]acetic acid (41) The reaction of 3-ethyl-4,8,8-tri-
methyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (14) (1 g, 3.06 mmol) with ethyl
2-azidoacetate (20) (0.47 g, 3.67 mmol) followed by
hydrolysis gave the title compound 41 as a light yellow
solid (0.82 g, 87 %) by following the general procedure;
mp 174–175 °C; Rf (MeOH:CHCl3::1:19) 0.32; mmax
(KBr)/cm-1 3422, 2973, 2940, 1744 (C=O), 1701 (C=O),
1611, 1571; kmax (MeOH)/nm 331; 1H (400 MHz, DMSO-
d6): d 1.00 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.28 (s, 6H, 29 C-8
CH3), 1.77 (t, 2H, J = 7.3 Hz, H-7), 2.32 (s, 3H, C-4 CH3),
2.52 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.78 (t, 2H, J = 7.3 Hz,
H-6), 5.10 (s, 2H, H-100), 5.24 (s, 2H, H-4a), 7.26 (s, 1H,
H-5), 8.11 (s, 1H, H-50), 13.33 (brs, 1H, COOH); 13C
(100.5 MHz, DMSO-d6): d 13.0 (C-2¢¢¢), 14.4 (C-4 CH3),
20.3 (C-1¢¢¢), 21.7 (C-6), 26.5 (29 C-8 CH3), 31.7 (C-7)
50.4 (C-100), 65.5 (C-4a), 75.7 (C-8), 113.2, 118.4, 119.9,
123.6, 126.0, 132.6, 143.1, 144.2, 146.5 & 149.1 (C-3–C-5,
C-10–C-14, C-40 & C-50), 160.5 (C-2), 168.6 (C-200);
HRMS (ESI) m/z [M ? H]? Calculated for C22H25N3O6:
428.1777; found: 428.1817.
3-Ethyl-10-[(1-hexyl-1H-1,2,3-triazol-4-yl)methoxy]-4,8,8-
trimethyl-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one
(39) The reaction of 3-ethyl-4,8,8-trimethyl-10-(prop-2-
yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-2(6H)-one
(14) (1 g, 3.06 mmol) with 1-azidohexane (19) (0.47 g,
3.67 mmol) gave the title compound 39 as a yellow solid
(0.69 g, 50 %) by following the general procedure; mp
109–110 °C; Rf (MeOH:CHCl3::1:49) 0.37; mmax (KBr)/
cm-1 2965, 2933, 1705 (C=O), 1610, 1571; kmax (MeOH)/
nm 329; 1H (400 MHz, CDCl3): d 0.86 (t, 3H, J = 7.3 Hz,
H-600), 1.11 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.25–1.32 (m, 6H,
H-300–H-500), 1.39 (s, 6H, 29 C-8 CH3), 1.84 (t, 2H,
J = 6.5 Hz, H-7), 1.87-1.92 (m, 2H, H-200), 2.33 (s, 3H,
C-4 CH3), 2.63 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.83 (t, 2H,
J = 6.5 Hz, H-6), 4.33 (t, 2H, J = 7.3 Hz, H-100), 5.29 (s,
2H, H-4a), 7.03 (s, 1H, H-5), 8.03 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.2 (C-2¢¢¢), 13.9 (C-600), 14.6 (C-
4 CH3), 20.8 (C-1¢¢¢), 22.4 (C-6 & C-500), 26.9 (29 C-8
CH3), 26.1, 30.2 & 31.1 (C-200–C-400), 32.5 (C-7), 50.4 (C-
100), 67.4 (C-4a), 76.4 (C-8), 113.9, 118.2, 119.3, 123.5,
124.7, 133.7, 145.0, 145.8 & 149.6 (C-3–C-5, C-10–C-14,
C-40 & C-50), 161.5 (C-2); HRMS (ESI) m/z [M ? H]?
Calculated for C26H35N3O4: 454.2661; found: 454.2701.
3-Ethyl-10-[(1-(3-fluorophenyl)-1H-1,2,3-triazol-4-yl)me-
thoxy]-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (42) The reaction of 3-ethyl-4,8,8-trimethyl-
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (14) (1 g, 3.06 mmol) with 1-azido-3-fluoroben-
zene (21) (0.50 g, 3.67 mmol) gave the title compound 42
as a light yellow solid (0.85 g, 60 %) by following the
general procedure; mp 157–158 °C; Rf (MeOH:
CHCl3::1:49) 0.34; mmax (KBr)/cm-1 2974, 1698 (C=O),
Ethyl 2-[4-(((7-ethyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahy-
dropyrano[3,2-g]chromen-10-yl)oxy) methyl)-1H-1,2,3-tri-
azol-1-yl]acetate (40) The reaction of 3-ethyl-4,8,8-
trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (14) (1 g, 3.06 mmol) with ethyl
2-azidoacetate (20) (0.47 g, 3.67 mmol) gave the title
compound 40 as a brown solid (1.00 g, 72 %) by following
the general procedure; mp 145–146 °C; Rf (MeOH:
CHCl3::1:49) 0.34; mmax (KBr)/cm-1 2966, 1755 (C=O),
1
1613, 1576; kmax (MeOH)/nm 330; H (400 MHz, CDCl3):
d 1.10 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.40 (s, 6H, 200 C-8 CH3),
1.85 (t, 2H, J = 6.5 Hz, H-7), 2.34 (s, 3H, C-4 CH3), 2.64
(q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.84 (t, 3H, J = 6.5 Hz, H-6),
5.38 (s, 2H, H-4a), 7.06 (s, 1H, H-5), 7.10–7.15 (m, 1H,
H-200), 7.47-7.53 (m, 1H, H-400), 7.59-7.65 (m, 2H, H-500 &
H-600), 8.59 (s, 1H, H-50); 13C (100.5 MHz, CDCl3): d 13.1
(C-2¢¢¢), 14.5 (C-4 CH3), 20.8 (C-1¢¢¢), 22.4 (C-6), 26.8 (29
C-8 CH3), 32.4 (C-7), 67.3 (C-4a), 75.9 (C-8), 108.2 (d,
J = 25.8 Hz, C-400), 115.4 (d, J = 21.0 Hz, C-200), 115.7 (d,
J = 2.8 Hz, C-600), 131.2 (d, J = 9.5 Hz, C-500), 138.3 (d,
J = 10.5 Hz, C-100), 113.9, 118.3, 119.5, 121.9, 124.8,
133.7, 144.6, 145.9, 146.2 & 149.5 (C-3–C-5, C-10–C-14,
C-40 & C-50), 161.6 (C-2), 163.1 (d, J = 248.2 Hz, C-300);
1
1706 (C=O), 1572; kmax (MeOH)/nm 329; H (400 MHz,
CDCl3): d 1.10 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.29 (t, 3H,
J = 7.3 Hz, H-20000), 1.40 (s, 6H, 29 C-8 CH3), 1.85 (t, 2H,
J = 6.5 Hz, H-7), 2.32 (s, 3H, C-4 CH3), 2.62 (q, 2H,
J = 7.3 Hz, H-1¢¢¢), 2.83 (t, 2H, J = 6.5 Hz, H-6), 4.25 (q,
2H, J = 7.3 Hz, H-10000), 5.15 (s, 2H, H–l00), 5.32 (s, 2H,
H-4a), 7.03 (s, 1H, H-5), 8.16 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.1 (C-2¢¢¢), 14.0 (C-20000), 14.5 (C-
4 CH3), 20.7 (C-1¢¢¢), 22.3 (C-6), 26.8 (29 C-8 CH3), 32.4
(C-7), 50.8 (C-100), 62.2 (C-10000), 67.1 (C-4a), 75.8 (C-8),
113.8, 118.2, 119.3, 124.6, 125.3, 133.6, 144.6, 145.4,
123

Med Chem Res
HRMS (ESI) m/z [M ? H]? Calculated for C26H26FN3O4:
pyran-3,4,5-triyl triacetate (45) The reaction of 3-ethyl-
4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano
[3,2-g] chromen-2(6H)-one (14) (1 g, 3.06 mmol) with
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl azide (24)
(1.37 g, 3.67 mmol) gave the title compound 45 as a light
yellow solid (1.46 g, 68 %) by following the general
procedure; mp 184–185 °C; Rf (MeOH:CHCl3::1:49) 0.35;
mmax (KBr)/cm-1 2974, 1752 (C=O), 1701 (C=O), 1611;
464.1941; found: 464.1988.
3-Ethyl-10-[(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)
methoxy]-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (43) The reaction of 3-ethyl-4,8,8-trimethyl-
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (14) (1 g, 3.06 mmol) with 1-azido-4-methoxy-
benzene (22) (0.55 g, 3.67 mmol) gave the title compound
43 as a brown solid (0.98 g, 67 %) by following the general
procedure; mp 122–123 °C; Rf (MeOH:CHCl3::1:49) 0.32;
1
kmax (MeOH)/nm 329; H (400 MHz, CDCl3): d 1.11 (t,
3H, J = 7.3 Hz, H-2¢¢¢), 1.35 (s, 6H, 29 C-8 CH3),
1.79–1.84 (m, 5H, H-7 & COCH3), 2.02 (s, 3H, COCH3),
2.06 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 2.33 (s, 3H,
C-4 CH3), 2.64 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.82 (t, 2H,
J = 7.3 Hz, H-6), 3.97–4.02 (m, 1H, H-500), 4.14 (dd, 1H,
J = 1.8 Hz & 12.8 Hz, H-600a/H-600b), 4.27 (dd, 1H,
J = 2.4 Hz & 12.8 Hz, H-600a/H-600b), 5.23–5.26 (m, 1H,
H-400), 5.28 (d, 2H, J = 4.2 Hz, H-4a), 5.41 (t, 1H,
J = 9.1 Hz, H-300), 5.53 (t, 1H, J = 9.7 Hz, H-200), 5.85 (d,
1H, J = 9.7 Hz, H-100), 7.04 (s, 1H, H-5), 8.21 (s, 1H,
H-50); 13C (100.5 MHz, CDCl3): d 13.1 (C-2¢¢¢), 14.5 (C-4
CH3), 20.2 (COCH3), 20.5 (29 COCH3), 20.7 (COCH3),
20.8 (C-1¢¢¢), 22.4 (C-6), 26.7 (C-8 CH3), 26.8 (C-8 CH3),
32.4 (C-7), 61.6 (C-600), 66.9 (C-400), 67.7 (C-4a), 70.2,
72.8 & 75.0 (C-200, C-300 & C-500), 75.7 (C-8), 85.6 (C-100),
113.9, 118.1, 119.3, 122.4, 124.9, 133.7, 144.6, 145.6,
145.8 & 149.3 (C-3–C-5, C-10–C-14, C-40 & C-50), 161.4
(C-2), 168.7 (COCH3), 169.3 (COCH3), 170.0 (COCH3),
170.6 (COCH3); HRMS (ESI) m/z [M ? H]? Calculated
for C34H41N3O13: 700.2712; found: 700.2700.
m
max (KBr)/cm-1 2970, 2930, 1697 (C=O), 1611, 1522; kmax
(MeOH)/nm 330; 1H (400 MHz, CDCl3): d 1.10 (t, 3H,
J = 7.3 Hz, H-2¢¢¢), 1.39 (s, 6H, 29 C-8 CH3), 1.85 (t, 2H,
J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4 CH3), 2.64 (q, 2H,
J = 7.3 Hz, H-1¢¢¢), 2.84 (t, 2H, J = 6.5 Hz, H-6), 3.86 (s,
3H, OCH3) 5.37 (s, 2H, H-4a), 7.02 (d, 2H, J = 8.7 Hz, H-300
& H-500), 7.05 (s, 1H, H-5), 7.70 (d, 2H, J = 8.7 Hz, H-200 &
H-600), 8.46 (s, 1H, H-50); 13C (100.5 MHz, CDCl3): d 13.2
(C-2¢¢¢), 14.6 (C-4 CH3), 20.8 (C-1¢¢¢), 22.4 (C-6), 26.8 (29
C-8 CH3), 32.5 (C-7), 55.6 (OCH3), 67.3 (C-4a), 75.8 (C-8),
114.7 (C-300 & C-500), 122.1 (C-200 & C-600), 113.9, 118.2,
119.4, 124.7, 130.6, 133.7, 144.7, 145.6, 145.9 & 149.5 (C-
3–C-5, C-10–C-14, C-40, C-50 & C-100), 159.6 (C-400), 161.6
(C-2); HRMS (ESI) m/z [M ? H]? Calculated for
C27H29N3O5: 476.2180; found: 476.2167.
10-[(1-(1,3-Dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)me-
thoxy]-3-ethyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chro-
men-2(6H)-one (44) The reaction of 3-ethyl-4,8,8-
trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-
g] chromen-2(6H)-one (14) (1 g, 3.06 mmol) with 2-azi-
dopropane-1,3-diol (23) (0.43 g, 3.67 mmol) gave the title
compound 44 as a light green solid (0.81 g, 58 %) by
following the general procedure; mp 71–72 °C; Rf
(MeOH:CHCl3::1:19) 0.32; mmax (KBr)/cm-1 3398, 2971,
3-Ethyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-
yl)-1H-1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,
2-g]chromen-2(6H)-one (46) The reaction of 3-ethyl-
4,8,8-trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano
[3,2-g] chromen-2(6H)-one (14) (1 g, 3.06 mmol) with
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl azide (24)
(1.37 g, 3.67 mmol) followed by subsequent deacetylation
gave the title compound 46 as a brown solid (1.14 g,
70 %) by following the general procedure; mp 63–64 °C;
Rf (MeOH:CHCl3::1:9) 0.32; mmax (KBr)/cm-1 3377, 2931,
1670 (C=O), 1608, 1569; kmax (MeOH)/nm 330; 1H
(400 MHz, DMSO-d6): d 1.02 (t, 3H, J = 6.9 Hz, H-2¢¢¢),
1.32 (s, 6H, 29 C-8 CH3), 1.80 (t, 2H, J = 6.5 Hz, H-7),
2.35 (s, 3H, C-4 CH3), 2.54 (q, 2H, J = 7.3 Hz, H-1¢¢¢),
2.81 (t, 2H, J = 6.5 Hz, H-6), 3.19-3.25 (m, 1H, H-200),
3.35-3.43 (m, 3H, H-300, H-400 & H-600a/H-600b), 3.68 (dd,
1H, J = 5.8 Hz & 10.2 Hz, H-600a/H-600b), 3.72-3.80 (m,
1H, H-500), 4.61 (t, 1H, J = 5.7 Hz, OH), 5.11 (s, 2H,
H-4a), 5.16 (d, 1H, J = 5.8 Hz, OH), 5.29 (d, 1H,
J = 4.3 Hz, OH), 5.36 (d, 1H, J = 5.8 Hz, OH), 5.54 (d,
1H, J = 9.5 Hz, H-200), 7.29 (s, 1H, H-5), 8.36 (s, 1H,
H-50); 13C (100.5 MHz, DMSO-d6): d 13.1 (C-2¢¢¢), 14.4
1
2931, 1701(C=O), 1610, 1577; kmax (MeOH)/nm 329; H
(400 MHz, CDCl3): d 1.04 (t, 3H, J = 7.3 Hz, H-2¢¢¢), 1.46
(s, 6H, 29 C-8 CH3), 1.90 (t, 2H, J = 6.9 Hz, H-7), 2.32
(s, 3H, C-4 CH3), 2.55 (q, 2H, J = 7.3 Hz, H-1¢¢¢), 2.87 (t,
2H, J = 6.5 Hz, H-6), 3.80 (brs, 2H, OH), 4.06–4.15 (m,
4H, H-100 & H-300), 4.63-4.66 (m, 1H, H-200), 5.23 (s, 2H,
H-4a), 7.07 (s, 1H, H-5), 8.37 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.1 (C-2¢¢¢), 14.6 (C-4 CH3), 20.7
(C-1¢¢¢), 22.4 (C-6), 26.9 (29 C-8 CH3), 32.4 (C-7), 62.3 &
64.2 (C-100 & C-300), 65.8 (C-200), 66.7 (C-4a), 76.0 (C-8),
113.7, 118.8, 119.7, 124.2, 133.5, 144.6, 147.0 & 149.7 (C-
3–C-5, C-10–C-14, C-40 & C-50), 162.6 (C-2); HRMS
(ESI) m/z [M ? H]? Calculated for C23H29N3O6:
444.2129; found: 444.2139.
(2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-[4-(((7-ethyl-2,2,6-
trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-
10-yl)oxy]methyl)-1H-1,2,3-triazol-1-yl]tetrahydro-2H-
123

Med Chem Res
(C-4 CH3), 20.3 (C-1¢¢¢), 22.5 (C-6), 26.5 (C-8 CH3), 26.6
(C-8 CH3), 31.7 (C-7), 60.8 (C-600), 65.7 (C-4a), 69.6, 72.2,
75.8, 77.0 & 80.0 (C-8 & C-200–C-500), 87.5 (C-100), 113.3,
118.5, 120.0, 123.6, 123.7, 132.9, 143.2, 144.1, 146.7
&149.1 (C-3–C-5, C-10–C-14, C-40 & C-50), 160.6 (C-2);
HRMS (ESI) m/z [M ? H]? Calculated for C26H33N3O9:
532.2290; found: 532.2302.
116.0 (d, J = 22.0 Hz, C-300 & C- 500), 130.0 (d,
J = 8.6 Hz, C-200 & C-600), 130.6 (d, J = 3.8 Hz, C-100),
113.9, 118.2, 119.3, 123.6, 123.7, 133.6, 144.6, 145.7,
145.9 & 149.4 (C-3–C-5, C-10–C-14, C-40 & C-50), 161.6
(C-2), 162.8 (d, J = 247.2 Hz, C-400); HRMS (ESI) m/z
[M ? H]? Calculated for C31H36FN3O4: 534.2763; found:
534.2768.
10-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-3-hexyl-4,8,
8-trimethyl-7,8-dihydropyrano[3,2-g] chromen-2(6H)-one
(47) The reaction of 3-hexyl-4,8,8-trimethyl-10-(prop-2-
yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-2(6H)-one
(15) (1 g, 2.61 mmol) with (azidomethyl)benzene (16)
(0.42 g, 3.13 mmol) gave the title compound 47 as a red
solid (0.74 g, 55 %) by following the general procedure;
mp 135–136 °C; Rf (MeOH:CHCl3::1:49) 0.34; mmax
(KBr)/cm-1 2977, 2955, 1695 (C=O), 1610, 1572; kmax
3-Hexyl-4,8,8-trimethyl-10-[(1-(4-nitrobenzyl)-1H-1,2,3-tri-
azol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (49) The reaction of 3-hexyl-4,8,8-trimethyl-10-
(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (15) (1 g, 2.61 mmol) with 1-(azidomethyl)-4-
nitrobenzene (18) (0.56 g, 3.13 mmol) gave the title
compound 49 as an orange solid (0.92 g, 63 %) by fol-
lowing the general procedure; mp 142–143 °C; Rf
(MeOH:CHCl3::1:49) 0.35; mmax (KBr)/cm-1 2957, 2921,
1705 (C=O), 1610, 1570; kmax (MeOH)/nm 332; 1H
(400 MHz, CDCl3): d 0.88 (t, 3H, J = 6.5 Hz, H-6¢¢¢),
1.25–1.36 (m, 6H, H-3¢¢¢–H-5¢¢¢), 1.39 (s, 6H, 29 C-8 CH3),
1.41–1.48 (m, 2H, H-2¢¢¢), 1.84 (t, 2H, J = 6.5 Hz, H-7),
2.32 (s, 3H, C-4 CH3), 2.55 (t, 2H, J = 7.6 Hz, H-1¢¢¢), 2.83
(t, 2H, J = 6.5 Hz, H-6), 5.30 (s, 2H, H-1a), 5.64 (s, 2H,
H-4a), 7.04 (s, 1H, H-5), 7.40 (d, 2H, J = 8.7 Hz, H-200 &
H-600), 8.16 (s, 1H, H-50), 8.19 (d, 2H, J = 8.7 Hz, H-300 &
H- 500); 13C (100.5 MHz, CDCl3): d 14.1 (C-6¢¢¢), 14.8 (C-4
CH3), 22.4 & 22.6 (C-6 & C-5¢¢¢), 26.8 (29 C-8 CH3), 27.5,
28.8, 29.3 & 31.7 (C-1¢¢¢–C-4¢¢¢), 32.4 (C-7), 53.0 (C-1a),
67.2 (C-4a), 75.8 (C-8), 124.2 (C-200 & C-600), 128.6 (C-300
& C-500), 113.8, 118.3, 119.4, 123.5, 124.3, 133.6, 141.8,
144.5, 146.1, 146.2, 147.9 & 149.5 (C-3–C-5, C-10–C-14,
C-40, C-50, C-100 & C-400), 161.6 (C-2); HRMS (ESI) m/z
[M ? H]? Calculated for C31H36N4O6: 561.2668; found:
561.2697.
1
(MeOH)/nm 330; H (400 MHz, CDCl3): d 0.88 (t, 3H,
J = 7.3 Hz, H-6¢¢¢), 1.25–1.31 (m, 6H, H-3¢¢¢–H-5¢¢¢), 1.35
(s, 6H, 29 C-8 CH3), 1.44–1.51 (m, 2H, H-2¢¢¢), 1.81 (t, 2H,
J = 6.9 Hz, H-7), 2.31 (s, 3H, C-4 CH3), 2.58 (t, 2H,
J = 8.0 Hz, H-1¢¢¢), 2.81 (t, 2H, J = 6.5 Hz, H-6), 5.27 (s,
2H, H-1a), 5.51 (s, 2H, H-4a), 7.02 (s, 1H, H-5), 7.26–7.30
(m, 2H, H-200 & H-600), 7.32–7.37 (m, 3H, H-300–H-500),
7.96 (1H, s, H-50); 13C (100.5 MHz, CDCl3): d 14.1 (C-
6¢¢¢), 14.8 (C-4 CH3), 22.4 & 22.6 (C-6 & C-5¢¢¢), 26.8 (29
C-8 CH3), 27.5, 28.8, 29.3, 31.7 (C-1¢¢¢–C-4¢¢¢), 32.4 (C-7),
54.1 (C-1a), 67.2 (C-4a), 75.7 (C-8), 128.1 (C-200 & C-600),
129.0 (C-300 & C-500), 113.9, 118.1, 119.3, 123.6, 123.7,
128.6, 133.6, 134.7, 144.6, 145.5, 145.9 & 149.4 (C-3–C-5,
C-10–C-14, C-40, C-50, C-100 & C-400), 161.6 (C-2); HRMS
(ESI) m/z [M ? H]? Calculated for C31H37N3O4:
516.2857; found: 516.2863.
10-[(1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy]-3-
hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-2(6H)-
one (48) The reaction of 3-hexyl-4,8,8-trimethyl-10-
(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (15) (1 g, 2.61 mmol) with 1-(azidomethyl)-4-
fluorobenzene (17) (0.47 g, 3.13 mmol) gave the title
compound 48 as an off-white solid (0.95 g, 68 %) by fol-
lowing the general procedure; mp 185–186 °C; Rf
(MeOH:CHCl3::1:49) 0.37; mmax (KBr)/cm-1 2927, 1696
3-Hexyl-10-[(1-hexyl-1H-1,2,3-triazol-4-yl)methoxy]-4,8,
8-trimethyl-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-
one (50) The reaction of 3-hexyl-4,8,8-trimethyl-10-
(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g] chromen-
2(6H)-one (15) (1 g, 2.61 mmol) with 1-azidohexane (19)
(0.40 g, 3.13 mmol) gave the title compound 50 as a red
solid (0.93 g, 70 %) by following the general procedure;
mp 101–102 °C; Rf (MeOH:CHCl3::1:49) 0.38; mmax
(KBr)/cm-1 2929, 1696 (C=O), 1611, 1575; kmax (MeOH)/
nm 330; 1H (400 MHz, CDCl3): d 0.85–0.89 (m, 6H, H-600
& H-6¢¢¢), 1.25–1.36 (m, 12H, H-300–H-500 & H-3¢¢¢–H-5¢¢¢),
1.39 (s, 6H, 29 C-8 CH3), 1.44–1.51 (m, 2H, H-2¢¢¢), 1.84
(t, 2H, J = 6.5 Hz, H-7), 1.87–1.93 (m, 2H, H-200), 2.32 (s,
3H, C-4 CH3), 2.59 (t, 2H, J = 7.6 Hz, H-1¢¢¢), 2.83 (t, 2H,
J = 6.5 Hz, H-6), 4.33 (t, 2H, J = 7.3 Hz, H-100), 5.29 (s,
2H, H-4a), 7.03 (s, 1H, H-5), 8.03 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 13.9 & 14.07 (C-600 & C-6¢¢¢), 14.8
(C-4 CH3), 22.4 & 22.6 (C-6, C-500 & C-5¢¢¢), 26.8 (29 C-8
CH3), 26.1, 27.5, 28.8, 29.3, 30.2, 31.1, 31.7 (C-200–C-400 &
1
(C=O), 1610, 1575; kmax (MeOH)/nm 330; H (400 MHz,
CDCl3): d 0.88 (t, 3H, J = 7.3 Hz, H-6¢¢¢), 1.25–1.33 (m,
6H, H-3¢¢¢–H-5¢¢¢), 1.36 (s, 6H, 29 C-8 CH3), 1.43–1.52 (m,
2H, H-2¢¢¢), 1.82 (t, 2H, J = 6.5 Hz, H-7), 2.31 (s, 3H, C-4
CH3), 2.58 (t, 2H, J = 8.0 Hz, H-1¢¢¢), 2.82 (t, 2H,
J = 6.5 Hz, H-6), 5.27 (s, 2H, H-1a), 5.48 (s, 2H, H-4a),
7.01–7.05 (m, 3H, H-5, H-200 & H-600), 7.26–7.30 (m, 2H,
H-300 & H-500), 8.00 (s, 1H, H-50); 13C (100.5 MHz,
CDCl3): d 14.1 (C-6¢¢¢), 14.8 (C-4 CH3), 22.4 & 22.6 (C-6
& C-5¢¢¢), 26.8 (29 C-8 CH3), 27.5, 28.8, 29.3 & 31.7 (C-
1¢¢¢–C-4¢¢¢), 32.4 (C-7), 53.3 (C-1a), 67.3 (C-4a), 75.8 (C-8),
123

Med Chem Res
C-1¢¢¢–C-4¢¢¢), 32.5 (C-7), 50.4 (C-100), 67.3 (C-4a), 75.8 (C-
8), 113.9, 118.2, 119.3, 123.6, 133.7, 144.6, 145.0, 146.0 &
149.5 (C-3–C-5, C-10–C-14, C-40 & C-50), 161.7 (C-2);
HRMS (ESI) m/z [M ? H]? Calculated for C30H43N3O4:
510.3287; found: 510.3327.
C-40 & C-50), 160.6 (C-2), 168.5 (C-200); HRMS (ESI) m/z
[M ? H]? Calculated for C26H33N3O6: 484.2403; found:
484.2452.
10-[(1-(3-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy]-3-
hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (53) The reaction of 3-hexyl-4,8,8-trimethyl-
Ethyl 2-[4-(((7-hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahy-
dropyrano[3,2-g]chromen-10-yl)oxy) methyl)-1H-1,2,3-tri-
azol-1-yl]acetate (51) The reaction of 3-hexyl-4,8,8-
trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-
g] chromen-2(6H)-one (15) (1 g, 2.61 mmol) with ethyl
2-azidoacetate (20) (0.40 g, 3.13 mmol) gave the title
compound 51 as an off-white solid (0.83 g, 62 %) by
following the general procedure; mp 116–117 °C; Rf
(MeOH:CHCl3::1:49) 0.37; mmax (KBr)/cm-1 2955, 1758
(C=O), 1697 (C=O), 1571; kmax (MeOH)/nm 329; 1H
(400 MHz, CDCl3): d 0.88 (t, 3H, J = 7.3 Hz, H-6¢¢¢),
1.27–1.38 (m, 9H, H-20000, H-3¢¢¢–H-5¢¢¢), 1.39 (s, 6H, 29
C-8 CH3), 1.44–1.51 (m, 2H, H-2¢¢¢), 1.85 (t, 2H,
J = 6.5 Hz, H-7), 2.32 (s, 3H, C-4 CH3), 2.58 (t, 2H,
J = 7.3 Hz, H-1¢¢¢), 2.83 (t, 2H, J = 6.5 Hz, H-6), 4.25
(q, 2H, J = 7.3 Hz, H-10000), 5.15 (s, 2H, H-100), 5.31 (s,
2H, H-4a), 7.03 (s, 1H, H-5), 8.17 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 14.0 & 14.1 (C-6¢¢¢ & C-20000),
14.8 (C-4 CH3), 22.3 & 22.6 (C-6 & C-50000), 26.8 (29 C-8
CH3), 27.5, 28.8, 29.3, 31.7 (C-1¢¢¢–C-4¢¢¢), 32.4 (C-7),
50.8 (C-100), 62.2 (C-10000), 67.1 (C-4a), 75.8 (C-8), 113.8,
118.2, 119.3, 123.5, 125.4, 133.6, 144.6, 145.5, 146.0 &
149.4 (C-3–C-5, C-10–C-14, C-40 & C-50), 161.7 (C-2),
166.2 (C-200); HRMS (ESI) m/z [M ? H]? Calculated for
C28H37N3O6: 512.2716; found: 512.2754.
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chro-
men-2(6H)-one (15) (1 g, 2.61 mmol) with 1-azido-3-flu-
orobenzene (21) (0.43 g, 3.13 mmol) gave the title
compound 53 as a yellow solid (0.83 g, 60 %) by following
the general procedure; mp 139–140 °C; Rf (MeOH:
CHCl3::1:49) 0.36; mmax (KBr)/cm-1 2920, 1710 (C=O),
1610, 1457; kmax (MeOH)/nm 330; 1H (400 MHz, CDCl3):
d 0.87 (t, 3H, J = 6.5 Hz, H-6¢¢¢), 1.26–1.36 (m, 6H,
H-3¢¢¢–H-5¢¢¢), 1.40 (s, 6H, 29 C-8 CH3), 1.42–1.50 (m, 2H,
H-2¢¢¢), 1.85 (t, 2H, J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4
CH3), 2.60 (t, 2H, J = 7.3 Hz, H-1¢¢¢), 2.84 (t, 2H,
J = 6.5 Hz, H-6), 5.38 (s, 2H, H-4a), 7.05 (s, 1H, H-5),
7.10–7.15 (m, 1H, H-200), 7.47–7.52 (m, 1H, H-400),
7.59–7.65 (m, 2H, H-500 & H-600), 8.59 (s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 14.1 (C-6¢¢¢), 14.9 (C-4 CH3), 22.4
& 22.6 (C-6 & C-5¢¢¢), 26.8 (29 C-8 CH3), 27.5, 28.8, 29.3
& 31.7 (C-1¢¢¢–C-4¢¢¢), 32.4 (C-7), 67.3 (C-4a), 75.9 (C-8),
108.2 (d, J = 25.8 Hz, C-200), 115.4 (d, J = 22.0 Hz,
C-400), 115.7 (d, J = 2.8 Hz, C-600), 131.1 (d, J = 9.5 Hz,
C-500), 138.3 (d, J = 10.5 Hz, C-100), 113.9, 118.2, 119.5,
121.9, 123.6, 133.7, 144.6, 146.1, 146.2 & 149.4 (C-3–C-5,
C-10–C-14, C-40
&
C-50), 161.7 (C-2), 163.1 (d,
J = 248.2 Hz, C-300); HRMS (ESI) m/z [M ? H]? Calcu-
lated for C30H34FN3O4: 520.2567; found: 520.2606.
2-[4-(((7-Hexyl-2,2,6-trimethyl-8-oxo-2,3,4,8-tetrahydropy-
rano[3,2-g]chromen-10-yl)oxy) methyl)-1H-1,2,3-triazol-1-
yl]acetic acid (52) The reaction of 3-hexyl-4,8,8-tri-
methyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (15) (1 g, 2.61 mmol) with ethyl
2-azidoacetate (20) (0.40 g, 3.13 mmol) followed by
hydrolysis gave the title compound 52 as a yellow solid
(0.70 g, 90 %) by following the general procedure; mp
63–64 °C; Rf (MeOH:CHCl3::1:19) 0.33; mmax (KBr)/
cm-1 3449, 2927, 1701 (C=O), 1610, 1572; kmax
3-Hexyl-10-[(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)
methoxy]-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]chro-
men-2(6H)-one (54) The reaction of 3-hexyl-4,8,8-tri-
methyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (15) (1 g, 2.61 mmol) with 1-azido-4-
methoxybenzene (22) (0.47 g, 3.13 mmol) gave the title
compound 54 as an orange solid (0.95 g, 68 %) by fol-
lowing the general procedure; mp 125–126 °C; Rf
(MeOH:CHCl3::1:49) 0.35; mmax (KBr)/cm-1 2953, 2923,
1695 (C=O), 1610, 1521; kmax (MeOH)/nm 331; 1H
(400 MHz, CDCl3): d 0.87 (t, 3H, J = 6.5 Hz, H-6¢¢¢),
1.25-1.36 (m, 6H, H-3¢¢¢–H-5¢¢¢), 1.39 (s, 6H, 29 C-8 CH3),
1.43-1.50 (m, 2H, H-2¢¢¢), 1.84 (t, 2H, J = 6.5 Hz, H-7),
2.32 (s, 3H, C-4 CH3), 2.59 (t, 2H, J = 7.3 Hz, H-1¢¢¢), 2.84
(t, 2H, J = 6.5 Hz, H-6), 3.86 (s, 3H, OCH3), 5.37 (s, 2H,
H-4a), 7.01 (d, 2H, J = 8.7 Hz, H-300 & H-500), 7.04 (s, 1H,
H-5), 7.70 (d, 2H, J = 8.7 Hz, H-200 & H-600), 8.45 (s, 1H,
H-50); 13C (100.5 MHz, CDCl3): d 14.1 (C-6¢¢¢), 14.9 (C-4
CH3) 22.4 & 22.6 (C-6 & C-5¢¢¢), 26.8 (29 C-8 CH3), 27.5,
28.8, 29.3 & 31.7 (C-1¢¢¢–C-4¢¢¢), 32.5 (C-7), 55.6 (OCH3),
67.3 (C-4a), 75.8 (C-8), 114.7 (C-300 & C-500), 122.1 (C-200
& C-600), 113.9, 118.2, 119.4, 123.6, 130.6, 133.7, 144.7,
1
(MeOH)/nm 330; H (400 MHz, DMSO-d6): d 0.85 (t,
3H, J = 7.3 Hz, H-6¢¢¢), 1.22–1.27 (m, 6H, H-3¢¢¢–H-5¢¢¢),
1.30 (s, 6H, 29 C-8 CH3), 1.37–1.42 (m, 2H, H-2¢¢¢), 1.79
(t, 2H, J = 6.5 Hz, H-7), 2.33 (s, 3H, C-4 CH3), 2.51 (t,
2H, J = 6.5 Hz, H-1¢¢¢), 2.80 (t, 2H, J = 6.5 Hz, H-6),
5.11 (s, 2H, H-100), 5.25 (s, 2H, H-4a), 7.26 (s, 1H, H-5),
8.13 (s, 1H, H-50), 13.36 (brs, 1H, COOH); 13C
(100.5 MHz, DMSO-d6): d 13.9 (C-6¢¢¢), 14.7 (C-4 CH3),
21.7 & 22.1 (C-6 & C-5¢¢¢), 26.5 (29 C-8 CH3), 26.9,
28.2, 28.6 & 31.1 (C-1¢¢¢–C-4¢¢¢), 31.7 (C-7), 50.5 (C-100),
65.5 (C-4a), 75.7 (C-8), 113.2, 118.4, 119.9, 122.4, 126.0,
132.6, 143.0, 144.2, 146.7 & 149.1 (C-3–C-5, C-10–C-14,
123

Med Chem Res
145.6, 146.1 &149.5 (C-3–C-5, C-10–C-14, C-40, C-50 &
C-100), 159.6 (C-400), 161.7 (C-2). HRMS (ESI) m/z
[M ? H]? Calculated for C31H37N3O5: 532.2767; found:
532.2799.
4 CH3), 20.1 (COCH3), 20.5 (COCH3), 20.6 (COCH3),
22.3 (C-6), 22.5 (COCH3), 26.6 (C-1¢¢¢), 26.8 (29 C-8
CH3), 27.5 (C-2¢¢¢), 28.7 (C-3¢¢¢), 29.3 (C-4¢¢¢), 31.6 (C-
5¢¢¢), 32.4 (C-7), 61.5 (C-600), 66.9 (C-400), 67.6 (C-4a),
70.2, 72.8 & 74.9 (C-200, C-300 & C-500), 75.7 (C-8), 85.5
(C-100), 113.9, 118.0, 119.3, 122.4, 123.7, 133.6, 144.6,
145.8 & 149.2 (C-3–C-5, C-10–C-14, C-40 & C-50),
161.5 (C-2), 168.6 (COCH3), 169.2 (COCH3), 170.0
(COCH3), 170.5 (COCH3); HRMS (ESI) m/z [M ? H]?
Calculated for C38H49N3O13: 756.3299; found:
756.3332.
10-[(1-(1,3-Dihydroxypropan-2-yl)-1H-1,2,3-triazol-4-yl)me-
thoxy]-3-hexyl-4,8,8-trimethyl-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (55) The reaction of 3-hexyl-4,8,8-
trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chromen-2(6H)-one (15) (1 g, 2.61 mmol) with 2-azido-
propane-1,3-diol (23) (0.37 g, 3.13 mmol) gave the title
compound 55 as an off-white solid (0.69 g, 53 %) by fol-
lowing the general procedure; mp 126–127 °C; Rf
(MeOH:CHCl3::1:19) 0.32; mmax (KBr)/cm-1 3447, 2930,
1677 (C=O), 1607, 1571; kmax (MeOH)/nm 330; 1H
(400 MHz, CDCl3): d 0.87 (t, 3H, J = 7.3 Hz, H-6¢¢¢),
1.20–1.40 (m, 8H, H-2¢¢¢–H-5¢¢¢), 1.46 (s, 6H, 29 C-8 CH3),
1.89 (t, 2H, J = 7.3 Hz, H-7), 2.31 (s, 3H, C-4 CH3), 2.52
(t, 2H, J = 7.6 Hz, H-1¢¢¢), 2.86 (t, 2H, J = 7.3 Hz, H-6),
4.08–4.19 (m, 4H, H-100 & H-300), 4.65–4.69 (m, 1H, H-200),
5.23 (s, 2H, H-4a), 7.06 (s, 1H, H-5), 8.47(s, 1H, H-50); 13C
(100.5 MHz, CDCl3): d 14.0 (C-6¢¢¢), 14.8 (C-4 CH3), 22.3
& 22.5 (C-6 & C-5¢¢¢), 26.9 (29 C-8 CH3), 27.3, 28.7, 29.2
& 31.6 (C-1¢¢¢–C-4¢¢¢), 32.4 (C-7), 62.1 (C-100 & C-300), 64.3
(C-200), 66.6 (C-4a), 75.9 (C-8), 113.7, 118.6, 119.6, 123.0,
133.4, 144.5, 147.1 & 149.6 (C-3–C-5, C-10–C-14, C-40 &
C-50), 162.6 (C-2); HRMS (ESI) m/z [M ? H]? Calculated
for C27H37N3O6: 500.2716; found: 500.2770.
3-Hexyl-4,8,8-trimethyl-10-[(1-((2R,3R,4S,5S,6R)-3,4,5-
trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl)-1H-
1,2,3-triazol-4-yl)methoxy]-7,8-dihydropyrano[3,2-g]chromen-
2(6H)-one (57) The reaction of 3-hexyl-4,8,8-trimethyl-
10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-g]
chro-
men-2(6H)-one (15) (1 g, 2.61 mmol) with 2,3,4,6-tetra-O-
acetyl-b-D-glucopyranosyl azide (24) (1.17 g, 3.13 mmol)
followed by subsequent deacetylation gave the title com-
pound 57 as a yellow solid (1.08 g, 70 %) by following the
general procedure; mp 144–145 °C; Rf (MeOH:
CHCl3::1:9) 0.32; mmax (KBr)/cm-1 3397, 2926, 1700
1
(C=O), 1610, 1571; kmax (MeOH)/nm 331; H (400 MHz,
DMSO-d6): d 0.85 (t, 3H, J = 7.3 Hz, H-6¢¢¢), 1.24–1.28
(m, 6H, H-2¢¢¢–H-4¢¢¢), 1.32 (s, 6H, 29 C-8 CH3), 1.37–1.44
(m, 2H, H-5¢¢¢), 1.80 (t, 2H, J = 7.3 Hz, H-7), 2.34 (s, 3H,
C-4 CH3), 2.52 (t, 2H, J = 7.3 Hz, H-1¢¢¢), 2.81 (t, 2H,
J = 7.3 Hz, H-6), 3.19–3.25 (m, 1H, H-200), 3.35–3.43 (m,
3H, H-3, H-400 & H-600a/H-600b), 3.68 (dd, 1H, J = 5.8 Hz
& 9.5 Hz, H-600a/H-600b), 3.72-3.80 (m, 1H, H-500) 4.61 (t,
1H, J = 5.2 Hz, OH), 5.10 (s, 2H, H-4a), 5.15 (d, 1H,
J = 6.5 Hz, OH), 5.28 (d, 1H, J = 4.3 Hz, OH), 5.36 (d,
1H, J = 5.8 Hz, OH), 5.54 (d, 1H, J = 9.5 Hz, H-100), 7.28
(s, 1H, H-5), 8.35 (s, 1H, H-50); 13C (100.5 MHz, DMSO-
d6): d 14.0 (C-6¢¢¢), 14.7 (C-4 CH3), 21.7 & 22.1 (C-6 &
C-5¢¢¢), 26.5 (C-8 CH3), 26.6 (C-8 CH3), 26.8, 28.3, 28.7,
31.1 & 31.7 (C-7 & C-1¢¢¢–C-4¢¢¢), 60.8 (C-600), 65.7 (C-4a),
69.6, 72.1, 75.8, 77.0, 80.0 (C-8 & C-200–C-500), 87.5 (C-
100), 113.3, 118.5, 120.0, 122.4, 123.7, 132.9, 143.2, 144.1,
146.9 &149.1 (C-3–C-5, C-10–C-14, C-40 & C-50), 160.7
(C-2); HRMS (ESI) m/z [M ? H]? Calculated for
C30H41N3O9: 588.2916; found: 588.2912.
(2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-[4-(((7-hexyl-2,2,6-
trimethyl-8-oxo-2,3,4,8-tetrahydropyrano[3,2-g]chromen-
10-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl]tetrahydro-2H-pyran-
3,4,5-triyl triacetate (56) The reaction of 3-hexyl-4,8,8-
trimethyl-10-(prop-2-yn-1-yloxy)-7,8-dihydropyrano[3,2-
g] chromen-2(6H)-one (15) (1 g, 2.61 mmol) with 2,3,4,6-
tetra-O-acetyl-b-D-glucopyranosyl azide (24) (1.17 g,
3.13 mmol) gave the title compound 56 as an off-white solid
(1.29 g, 65 %) by following the general procedure; mp
184–185 °C; Rf (MeOH:CHCl3::1:49) 0.37; mmax (KBr)/
cm-1 2957, 2929, 1754 (C=O), 1700 (C=O), 1611, 1572;
1
kmax (MeOH)/nm 331; H (400 MHz, CDCl3): d 0.88 (t,
3H, J = 6.9 Hz, H-6¢¢¢), 1.24–1.31 (m, 6H, H-2¢¢¢–H-
4¢¢¢), 1.36 (s, 6H, 29 C-8 CH3), 1.45-1.53 (m, 2H, H-5¢¢¢),
1.82 (t, 2H, J = 7.3 Hz, H-7), 1.85 (s, 3H, COCH3), 2.03
(s, 3H, COCH3), 2.06 (s, 3H, COCH3), 2.09 (s, 3H,
COCH3), 2.33 (s, 3H, C-4 CH3), 2.60 (t, 2H, J = 7.3 Hz,
H-1¢¢¢), 2.82 (t, 2H, J = 7.3 Hz, H-6), 3.99 (ddd, 1H,
J = 2.2 Hz, 5.1 Hz & 10.2 Hz, H-500), 4.15 (dd, 1H,
J = 1.4 Hz & 12.4 Hz, H-600a/H-600b), 4.28 (dd, 1H,
J = 5.1 Hz & 12.4 Hz, H-600a/H-600b), 5.24–5.26 (m, 1H,
H-400), 5.29 (d, 2H, J = 4.3 Hz, H-4a), 5.41 (t, 1H,
J = 9.5 Hz, H-300), 5.54 (t, 1H, J = 9.1 Hz, H-200), 5.86
(d, 1H, J = 9.5 Hz, H-100), 7.04 (s, 1H, H-5), 8.20 (s, 1H,
H-50); 13C (100.5 MHz, CDCl3): d 14.0 (C-6¢¢¢), 14.8 (C-
Biology
Pathogens
The pathogenic strains of bacteria, namely Bacillus cereus
(MTCC 430), Bacillus subtilis (MTCC 121), Staphylo-
coccus aureus (MTCC 740), Escherichia coli (MTCC
1586), Pseudomonas aeruginosa (MTCC 741), Klebsiella
pneumoniae (MTCC 3384), Salmonella enterica
123

Med Chem Res
typhimurium (MTCC 98), were procured from Institute of
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tance from Defense Research Development Organization (DRDO,
Delhi) and University of Delhi for the DU-DST PURSE Grant and
CSIR—TOUCH (BSC0302) project. The authors SK, SP and BK are
also thankful to CSIR, New Delhi, for the financial support (JRF/
SRF).
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