An efficient synthesis of novel bis-1,3,4-thiadiazolyl-carbamate derivatives based on deoxycholic acid under microwave irradiation

Article abstract of DOI:10.3184/174751912X13319206588494

An easy and efficient method for the synthesis of novel deoxycholic acid bis-1,3,4-thiadiazol-carbamate derivatives under microwave irradiation has been developed. Twelve new methyl 3α,12α-bis-[(5-aryl-1,3,4-thiadiazol-2- yl) carbamoyloxy]-cholan-24-oates

Full text of DOI:10.3184/174751912X13319206588494

218 RESEARCH PAPER
APRIL, 218–221
JOURNAL OF CHEMICAL RESEARCH 2012
An efficient synthesis of novel bis-1,3,4-thiadiazolyl-carbamate
derivatives based on deoxycholic acid under microwave irradiation
Zhigang Zhao*, Lin Li, Min Liu and Qinggang Mei
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. China
An easy and efficient method for the synthesis of novel deoxycholic acid bis-1,3,4-thiadiazol-carbamate derivatives
under microwave irradiation has been developed. Twelve new methyl 3α,12α-bis-[(5-aryl-1,3,4-thiadiazol-2-yl)
carbamoyloxy]-cholan-24-oates were obtained in better yield (78–91%) and shorter time (15–22 min). Their structures
were identified by 1H NMR, IR, MS spectra and elemental analyses.
Keywords: deoxycholic acid, bis-1,3,4-thiadiazoles, microwave irradiation, biological activities
Heterocyclic compounds hold a special place among
pharmaceutically significant natural products and synthetic
compounds. An important class of nitrogen heterocycles,
1,3,4-thiadiazole derivatives, have attracted attention for a
long time due to their broad spectrum of biological activities,
such as antibacterial,1,2 anti-fungal,3 anti-diabetic,4 anti-inflam-
matory,5 analgesic,6 anti-depressant,7 anti-tumour,8 anti-convulsant9
and plant growth regulatory10 activity. Some new substituted
1,3,4-thiadiazoles11 have also been found to possess high
anti-proliferative activity against the cells of human cancer
lines. Furthermore, the thiadiazole moiety is widely distrib-
uted in natural substances and synthetic drugs.Acetazolamide12
as a well-known therapeutically effective inhibitor containing
1,3,4-thiadiazole ring, has encouraged synthesis of further
structural derivatives with the aim of getting more potent lead
molecules.
Recently, moreover, several novel nitrogen derivatives based
on steroids have been synthesised, including some amino
cholesterol derivatives which exhibit significant anti-microbial
activity.13,14 Aher et al.15 have designed a class of steroid-
polyamine conjugates which were found to display anti-bacte-
rial activity comparable to gentamicin against S. aureus. Most
of these conjugates, however, were just polyamines attached
at different positions of the steroid ring whereas very few
heterocyclic rings were introduced. Bulbul16 and co-workers
have described the significant inhibition efficacy of their
synthetic bile-acid 1,3,4-thiadiazoles and extremely useful
leads in the process of drug discovery. Nevertheless, these
compounds contained only one 1,3,4-thiadiazole nucleus on
the side chain, and the preparation required a prolonged
reaction time of 12~48 h. It was therefore considered worth-
while to prepare new bile acid-based bis-amino-1,3,4-thiadia-
zoles with potentialbiological activity. Deoxycholic acid has
been chosen here because of its availability and useful level of
functionalisation. Bile acids are pharmacologically interesting
aspotentialcarrierofliver-specificdrugs,absorptionenhancers,
and colesterol-lowering agents.17,18 Some cholic acid-derived
facial amphiphiles have been reported to facilitate the
permeability of membranes including bacterial cell wall.19 As
a part of our ongoing work on bile acids20 we designed bile
acid-carbamate derivatives in which two 1,3,4-thiadiazole
nuclei have been introduced through a carbonyl bridge at the
3- and 12-O positions of steroid unit. We anticipated that these
new molecules might have a potent antibacterial activity.
With the development of green chemistry, the application of
microwave techniques for organic synthesis is rapidly becoming
popular.21,22 Shorter reaction times and higher product yields
are some of the advantages that render this procedure a greener
alternative to traditional chemical synthesis. In our previous
work,23 it was found that by using microwave irradiation, ester
and carbamates based on deoxycholic acid can be successfully
synthesised in shorter times and in better yields compared to
the conventional method. Extending the research in this area,
we now report an easy, rapid and efficient synthetic method
of bis-1,3,4-thiadiazolyl-carbamate derivatives derived from
deoxycholic acid under microwave irradiation which, as far as
we know, has not been attempted previously. The synthesis of
title compounds is outlined in Scheme 1.
Results and discussion
The structures of all the compounds 6a–l were established by
elemental analyses in addition to IR, 1H NMR, and MS spectral
data and were in full agreement with their structures. The
IR spectrum of these compounds exhibited characteristic
absorption bands in the region 3169–3160 cm-1 due to the NH
stretching frequency. The strong bands falling within the range
of 1728–1724 cm−1 indicated the absorption of C=O. The
strong absorption bands at about 1540, 1234, and 690 cm−1
were assigned to the C=N, C=N-N, and C-S-C functions of
1
the thiadiazole ring, respectively. In the H NMR spectra,
two singlets each belonging to two different NH groups
were observed at 12.56–12.15 and 12.37–11.96 ppm, which
appeared in much lower downfield compared to average amide
structure. The aromatic protons derived from aryl group
resonated between 8.67 and 7.05 ppm. In addition, two singlets
around 0.94 ppm, 0.74 ppm and one doublet in the range
of 0.81–0.78 ppm having coupling constant 6.4 Hz were
characteristic of the steroidal structure. The singlet at 3.56–
3.54 ppm was attributed to the three protons of ester methyl
moiety. Their mass spectra exhibited the expected molecular
ion peaks with high intensity.
The microwave-enhanced method was found to be efficient
in the preparation of carbamate type compounds based on
deoxycholic acid in comparison with the conventional method
(Table 1). MWI greatly decreased the reaction time from 360–
600 min to 15–22 min, and hence the reaction rate increased
23–34 times. Furthermore, the yields increased from 41–57%
to 78–91%. Consequently, the use of microwave technology
allows expeditious and efficient procedures in organic
synthesis.
The compounds 6a–e were tested for their antibacterial
activities by a disc-diffusion method using a nutrient broth
medium. The Gram-positive and Gram-negative bacteria
utilized in this study consisted of S. typhimurium, S. pyogenes,
E.coli. In the disc-diffusion method, sterile paper discs (5 mm)
were impregnated with compound dissolved in DMSO at con-
centration 0.01% (mass fraction). The plates were incubated
at 35 °C for 24 h. The result is presented in Table 2. The
compounds investigated have good biological activity against
E. coli. Further antibacterial activities are under study.
Experimental
Melting points were measured on a micro-melting point apparatus and
are uncorrected. IR spectra were obtained with a 1700 Perkin-Elmer
* Correspondent. E-mail: zzg63129@yahoo.com.cn

JOURNAL OF CHEMICAL RESEARCH 2012 219
Scheme 1 Reagents and conditions: (i) 1,4-dioxane, POCl3; (ii) CH3OH, CH3COCl; (iii) CH2Cl2, CO(OCCl3)2, pyridine, MWI;
(iv) pyridine, MWI.
1
FTIR in KBr disks. H NMR spectra were recorded on a Varian
INOVA 400 MHz spectrometer using DMSO-d6 as applied solvent
and TMS as internal standard at ambient temperature. Mass spectra
were determined on Finnigan LCQDECA instrument. Elemental analyses
were carried out on a Carlo-Erba-1106 autoanalyser. Optical rotations
were measured with a Wzz-2B polarimeter. Microwave irradiation
was performed in open containers with a commercial microwave
reactor (XH-100A, 100-1000 W, Beijing Xianghu Science and
Technology Development Co. Ltd, Beijing, P.R. China). All the
solvents were purified before use. Deoxycholic acid 3 was converted
to methyl 3α,12α-dihydroxycholan-24-oate 4 following the reported
procedure.24
General procedure for the preparation of 5-aryl-1,3,4-thiadiazol-2-
amines (2a–l)25
Phosphorous oxychloride (1 mL) was added at 0–5 °C dropwise with
stirring to a mixture of substituted benzoic acid 1 (12 mmol) and
thiosemicarbazide (10 mmol) in 1,4-dioxane (10 mL), and maintained
for 20 min. The temperature of the contents was allowed to gradually
rise to 75 °C, and stirred for 2 h. After cooling to room temperature,
ice cold water (8 mL) was added cautiously and the mixture was
refluxed 3 h. On cooling, the reaction mixture was poured into
ice-water with constant stirring and the pH was adjusted to the range
of 8–9 by addition of 10% NaOH solution. The precipitate which
formed was filtered off, washed with water, dried and recrystallised

220 JOURNAL OF CHEMICAL RESEARCH 2012
Table 1 Comparison of the synthesis of compounds 6a–l
between microwave irradiation and conventional heating
Table 3 The melting points of 5-aryl-1,3,4-thiadiazol-2-amines
2a–l
Compd Conventional method Microwave method TC/TMW
Product
Formula
M.p./ °C
Lit M.p./ °C
Time/min
Yield/%
Time/
min
Yield/%
2a
2b
2c
2d
2e
2f
2g
2h
2i
C8H7N3S
C9H9N3S
229–231
221–222
189–191
207–209
224–226
196–198
219–221
252–253
231–232
193–194
194–196
176–178
231.5–232.826
215–21627
210–21228
210–21229
22730
C9H9N3S
6a
6b
6c
6d
6e
6f
6g
6h
6i
360
480
450
510
570
540
600
540
600
420
540
480
55
48
45
57
48
46
41
53
43
51
52
49
15
18
18
16
17
17
21
20
22
18
18
21
91
83
84
90
81
83
78
87
82
83
86
81
24
27
25
32
34
32
29
27
27
23
30
23
C8H6FN3S
C8H6ClN3S
C8H6ClN3S
C8H6BrN3S
C8H6N4O2S
C8H6N4O2S
C9H9N3OS
C12H9N3S
C9H9N3OS
22630
222–22431
250–25231
242–2433
193.1–194.626
–
2j
2k
2l
183–18528
6j
6k
6l
NMR (400 MHz, DMSO-d6) δ: 12.30 (s, 1H, NH), 12.11 (s, 1H, NH),
7.78 (t, J = 8.8 Hz, 4H, ArH), 7.32 (d, J = 7.2 Hz, 4H, ArH), 5.07 (s,
1H, 12β-H), 4.68 (brs, 1H, 3β-H), 3.54 (s, 3H, COOCH3), 2.35 (s, 6H,
ArCH3), 0.94 (s, 3H, 19-CH3), 0.78 (d, J = 6.4 Hz, 3H, 21-CH3), 0.74
(s, 3H, 18-CH3); ESI-MS m/z (%): 863 [(M+23)+, 100]. Anal. Calcd
for C45H56N6O6S2: C, 64.26; H, 6.71; N, 9.99. Found: C, 64.13; H,
6.72; N, 10.04%.
TC, conventional method reaction time; TMW, microwave method
reaction time.
Table 2 Antibacterial activities of compounds 6a–e
Compounds S. typhimurium
S. pyogenes
E. coli
Methyl(3α,5β,12α)-3,12-bis-{[5-(3-methylphenyl)-1,3,4-thiadiazol-
2-yl]carbamoyloxy}-cholan-24-oate (6c): White crystal, yield 84%,
m.p. 179–181 °C; [α]2D0+215.0 (c 0.10, DMSO); IR (KBr) (cm−1):
3166, 2945, 2869, 1728, 1541, 1446, 1311, 1237, 1044, 781, 690;
1H NMR (400 MHz, DMSO-d6) δ: 12.33 (s, 1H, NH), 12.14 (s, 1H,
NH), 7.72 (d, J = 11.2 Hz, 2H, ArH), 7.67 (d, J = 9.2 Hz, 2H, ArH),
7.39 (t, J = 7.6 Hz, 2H, ArH), 7.32 (d, J = 7.2 Hz, 2H, ArH), 5.08
(s, 1H, 12β-H), 4.69 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 2.37 (s,
6H, ArCH3), 0.94 (s, 3H, 19-CH3), 0.78 (d, J = 6.4 Hz, 3H, 21-CH3),
0.74 (s, 3H, 18-CH3); ESI-MS m/z (%): 863 [(M+23)+, 100]. Anal.
Calcd for C45H56N6O6S2: C, 64.26; H, 6.71; N, 9.99. Found: C, 64.41;
H, 6.73; N, 9.92%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]
carbamoyloxy}-cholan-24-oate (6d): White crystal, yield 90%, m.p.
179–181 °C; [α]2D0+137.5 (c 0.12, DMSO); IR (KBr) (cm−1): 3164,
2947, 2870, 1728, 1549, 1454, 1316, 1231, 1044, 834, 702; 1H NMR
(400 MHz, DMSO-d6) δ: 12.36 (s, 1H, NH), 12.18 (s, 1H, NH), 7.99–
7.93 (m, 4H, ArH), 7.36 (t, J = 8.4 Hz, 4H, ArH), 5.07 (s, 1H, 12β-H),
4.69 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.94 (s, 3H, 19-CH3),
0.78 (d, J = 6.4 Hz, 3H, 21-CH3), 0.74 (s, 3H, 18-CH3); ESI-MS m/z
(%): 849 [(M+1)+, 100]. Anal. Calcd for C43H50F2N6O6S2: C, 60.83; H,
5.94; N, 9.90. Found: C, 60.62; H, 5.98; N, 9.96%.
6a
+
+
+
–
+
–
+
–
+
–
–
–
++
++
++
++
++
–
6b
6c
6d
6e
DMSO
++ strong; + moderate; – weak or none.
from etanol–water to afford white or off-white needles of 2. The purity
of compounds was analysed by TLC using petroleum ether-ethyl
acetate as mobile phase. The melting points of substituted thiadiazoles
2a–l are presented in Table 2.
5-(1-Naphthyl)-1,3,4-thiadiazol-2-amine (2k): Off-white needle
crystal, yield 83%, m.p. 194–196 °C; IR (KBr) (cm−1): 3281, 3112,
1629, 1509, 1333, 1278, 1050, 771, 681; 1H NMR (400 MHz, DMSO-
d6) δ: 8.80 (d, J = 8.4 Hz, 1H, ArH), 8.04 (t, J = 7.6 Hz, 2H, ArH), 7.75
(d, J = 7.2 Hz, 1H, ArH), 7.72–7.58 (m, 3H, ArH), 7.50 (s, 2H, NH);
ESI-MS m/z (%): 228 [(M+1)+, 100]. Anal. Calcd for C12H9N3S: C,
63.41; H, 3.99; N, 18.49. Found: C, 63.28; H, 3.96; N, 18.57%.
Microwave procedure for the preparation of compounds 6a–l
Dry pyridine (0.2 mL) was added to a solution of methyl deoxycholate
4 (0.6 mmol) and triphosgene (0.46 mmol) in dry CH2Cl2 (15 mL) at
room temperature. The reaction mixture was then subjected to
microwave irradiation at 200 W for 12 min to give the compound 5.
The amino-1,3,4-thiadiazoles 2 (1.8 mmol) and dry pyridine (0.2 mL)
were added directly to the mixture and the irradiation was continued
for 15–22 min at the same power. After complete conversión, as
indicated by TLC, the solvent was removed and the residue was
washed with 1% HCl, brine and finally dried in vacuum. The crude
product thus obtained was purified by column chromatography over
silica gel H using dichloromethane-ethyl acetate as the eluant to
provide the corresponding compounds 6. The physical and spectra
data of 6a–l are as follows.
Methyl(3α,5β,12α)-3,12-bis-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl-
oxy]-cholan-24-oate (6a): Colourless crystal, yield 91%, m.p. 181–
183 °C; [α]2D0+166.7 (c 0.12, DMSO); IR (KBr) (cm−1): 3167, 2945,
2869, 1727, 1540, 1450, 1310, 1234, 1041, 762, 690; 1H NMR
(400 MHz, DMSO-d6) δ: 12.35 (s, 1H, NH), 12.16 (s, 1H, NH), 7.92–
7.87 (m, 4H, ArH), 7.51 (t, J = 3.6 Hz, 6H, ArH), 5.08 (s, 1H, 12β-H),
4.69 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.94 (s, 3H, 19-CH3),
0.78 (d, J = 6.4 Hz, 3H, 21-CH3), 0.75 (s, 3H, 18-CH3); ESI-MS m/z
(%): 835 [(M+23)+, 100]. Anal. Calcd for C43H52N6O6S2: C, 63.52; H,
6.45; N, 10.34. Found: C, 63.41; H, 6.50; N, 10.36%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(4-chlorphenyl)-1,3,4-thiadiazol-2-yl]
carbamoyloxy}-cholan-24-oate (6e): White crystal, yield 81%, m.p.
189–191 °C; [α]2D0+104.2 (c 0.12, DMSO); IR (KBr) (cm−1): 3163,
2945, 2869, 1727, 1543, 1448, 1315, 1234, 1045, 826, 702; 1H NMR
(400 MHz, DMSO-d6) δ: 12.39 (s, 1H, NH), 12.21 (s, 1H, NH), 7.92
(t, J = 8.8 Hz, 4H, ArH), 7.59–7.56 (m, 4H, ArH), 5.08 (s, 1H, 12β-H),
4.69 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.94 (s, 3H, 19-CH3),
0.78 (d, J = 6.4 Hz, 3H, 21-CH3), 0.74 (s, 3H, 18-CH3); ESI-MS m/z
(%): 903 [(M+23)+, 100]. Anal. Calcd for C43H50Cl2N6O6S2: C, 58.56;
H, 5.71; N, 9.53. Found: C, 58.72; H, 5.65; N, 9.46%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(3-chlorphenyl)-1,3,4-thiadiazol-2-yl]
carbamoyloxy}-cholan-24-oate (6f): White solid, yield 83%, m.p.
190–192 °C; [α]2D0+240.9 (c 0.11, DMSO); IR (KBr) (cm−1): 3160,
2944, 2870, 1728, 1544, 1447, 1315, 1238, 1044, 772, 679; 1H NMR
(400 MHz, DMSO-d6) δ: 12.44 (s, 1H, NH), 12.25 (s, 1H, NH), 7.95
(d, J = 8.0 Hz, 2H, ArH), 7.88–7.83 (m, 2H, ArH), 7.59–7.52 (m, 4H,
ArH), 5.08 (s, 1H, 12β-H), 4.69 (brs, 1H, 3β-H), 3.55 (s, 3H,
COOCH3), 0.94 (s, 3H, 19-CH3), 0.78 (d, J = 6.4 Hz, 3H, 21-CH3),
0.74 (s, 3H, 18-CH3); ESI-MS m/z (%): 1785 [(2M+23)+, 100]. Anal.
Calcd for C43H50Cl2N6O6S2: C, 58.56; H, 5.71; N, 9.53. Found: C,
58.47; H, 5.74; N, 9.60%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(4-bromophenyl)-1,3,4-thiadiazol-
2-yl]carbamoyloxy}- cholan-24-oate (6g): White solid, yield 78%,
m.p. 185–187 °C; [α]2D0+195.5 (c 0.11, DMSO); IR (KBr) (cm−1):
3169, 2945, 2870, 1727, 1539, 1449, 1311, 1233, 1057, 824, 702; 1H
NMR (400 MHz, DMSO-d6) δ: 12.40 (s, 1H, NH), 12.21 (s, 1H, NH),
7.85 (t, J = 8.4 Hz, 4H, ArH), 7.73–7.70 (m, 4H, ArH), 5.08 (s, 1H,
12β-H), 4.69 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.94 (s, 3H,
Methyl(3α,5β,12α)-3,12-bis-{[5-(4-methylphenyl)-1,3,4-thiadiazol-
2-yl]carbamoyloxy}-cholan-24-oate (6b): White crystal, yield 83%,
m.p. 176–178 °C; [α]2D0+157.1 (c 0.14, DMSO); IR (KBr) (cm−1):
3167, 2944, 2869, 1728, 1540, 1451, 1311, 1233, 1041, 817, 709; 1H

JOURNAL OF CHEMICAL RESEARCH 2012 221
19-CH3), 0.78 (d, J = 6.4 Hz, 3H, 21-CH3), 0.74 (s, 3H, 18-CH3); ESI-
MS m/z (%): 993 [(M+23)+, 100]. Anal. Calcd for C43H50Br2N6O6S2:
C, 53.20; H, 5.19; N, 8.66. Found: C, 53.28; H, 5.16; N, 8.61%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(4-nitrophenyl)-1,3,4-thiadiazol-2-yl]
carbamoyloxy}-cholan-24-oate (6h): Pale yellow crystal, yield 87%,
m.p. 192–193 °C; [α]2D0+146.4 (c 0.14, DMSO); IR (KBr) (cm−1):
3162, 2945, 2869, 1726, 1532, 1446, 1344, 1231, 1045, 853, 690; 1H
NMR (400 MHz, DMSO-d6) δ: 12.56 (s, 1H, NH), 12.37 (s, 1H, NH),
8.35-8.32 (m, 4H, ArH), 8.18 (t, J = 8.8 Hz, 4H, ArH), 5.10 (s, 1H,
12β-H), 4.71 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.95 (s, 3H,
19-CH3), 0.80 (d, J = 6.4 Hz, 3H, 21-CH3), 0.76 (s, 3H, 18-CH3);
ESI-MS m/z (%): 925 [(M+23)+, 100]. Anal. Calcd for C43H50N8O10S2:
C, 57.19; H, 5.58; N, 12.41. Found: C, 57.08; H, 5.62; N, 12.46%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl]
carbamoyloxy}- cholan-24-oate (6i): White solid, yield 82%, m.p.
203–205 °C; [α]2D0+227.3 (c 0.11, DMSO); IR (KBr) (cm−1): 3169,
2945, 2871, 1724, 1535, 1446, 1309, 1236, 1044, 754, 707; 1H NMR
(400 MHz, DMSO-d6) δ: 12.52 (s, 1H, NH), 12.34 (s, 1H, NH), 8.07
(t, J = 6.4 Hz, 2H, ArH), 7.91–7.89 (m, 1H, ArH), 7.84 (t, J = 4.8 Hz,
3H, ArH), 7.82–7.80 (m, 1H, ArH), 7.77 (t, J = 7.2 Hz, 1H, ArH), 5.09
(s, 1H, 12β-H), 4.71 (brs, 1H, 3β-H), 3.55 (s, 3H, COOCH3), 0.94 (s,
3H, 19-CH3), 0.79 (d, J = 6.4 Hz, 3H, 21-CH3), 0.75 (s, 3H, 18-CH3);
ESI-MS m/z (%): 903 [(M+1)+, 100]. Anal. Calcd for C43H50N8O10S2:
C, 57.19; H, 5.58; N, 12.41. Found: C, 57.34; H, 5.52; N, 12.43%.
Methyl (3α,5β,12α)-3,12-bis-{[5-(4-methoxyphenyl)-1,3,4-thiadiazol-
2yl]carbamoyloxy}-cholan-24-oate (6j): White crystal, yield 83%,
m.p. 168–170 °C; [α]2D0+245.5 (c 0.11, DMSO); IR (KBr) (cm−1):
3169, 2944, 2871, 1727, 1543, 1455, 1308, 1244, 1037, 832, 706; 1H
NMR (400 MHz, DMSO-d6) δ: 12.26 (s, 1H, NH), 12.07 (s, 1H, NH),
7.83 (t, J = 10.0 Hz, 4H, ArH), 7.09–7.05 (m, 4H, ArH), 5.06 (s, 1H,
12β-H), 4.68 (brs, 1H, 3β-H), 3.82 (s, 6H, ArOCH3), 3.55 (s, 3H,
COOCH3), 0.94 (s, 3H, 19-CH3), 0.78 (d, J = 6.4 Hz, 3H, 21-CH3),
0.74 (s, 3H, 18-CH3); ESI-MS m/z (%): 873 [(M+1)+, 100]. Anal.
Calcd for C45H56N6O8S2: C, 61.90; H, 6.46; N, 9.63. Found: C, 61.74;
H, 6.49; N, 9.67%.
Methyl(3α,5β,12α)-3,12-bis-{[5-(1-naphthyl)-1,3,4-thiadiazol-2yl]
carbamoyloxy}-cholan-24-oate (6k): White solid, yield 86%, m.p.
193–195 °C; [α]2D0+162.5 (c 0.12, DMSO); IR (KBr) (cm−1): 3165,
2940, 2868, 1725, 1541, 1446, 1312, 1237, 1037, 775, 706; 1H NMR
(400 MHz, DMSO-d6) δ: 12.44 (s, 1H, NH), 12.27 (s, 1H, NH), 8.67–
8.60 (m, 2H, ArH), 8.11 (d, J = 8.0 Hz, 2H, ArH), 8.07–8.05 (m, 2H,
ArH), 7.90–7.83 (m, 2H, ArH), 7.68–7.61 (m, 6H, ArH), 5.10 (s, 1H,
12β-H), 4.72 (brs, 1H, 3β-H), 3.56 (s, 3H, COOCH3), 0.95 (s, 3H,
19-CH3), 0.81 (d, J = 6.4 Hz, 3H, 21-CH3), 0.76 (s, 3H, 18-CH3);
ESI-MS m/z (%): 935 [(M+23)+, 100]. Anal. Calcd for C51H56N6O6S2:
C, 67.08; H, 6.18; N, 9.20. Found: C, 67.21; H, 6.15; N, 9.11%.
Methyl (3α,5β,12α)-3,12-bis-{[5-(2-methoxyphenyl)-1,3,4-thiadiazol-
2yl]carbamoyloxy}-cholan-24-oate (6l): White crystal, yield 81%,
m.p. 172–173 °C; [α]2D0+208.3 (c 0.12, DMSO); IR (KBr) (cm−1):
3169, 2944, 2870, 1728, 1539, 1457, 1307, 1250, 1045, 757, 676; 1H
NMR (400 MHz, DMSO-d6) δ: 12.15 (s, 1H, NH), 11.96 (s, 1H, NH),
8.24 (t, J = 8.0 Hz, 2H, ArH), 7.51 (t, J = 8.0 Hz, 2H, ArH), 7.26 (t,
J = 8.0 Hz, 2H, ArH), 7.12 (t, J = 7.6 Hz, 2H, ArH), 5.07 (s, 1H, 12β-
H), 4.68 (brs, 1H, 3β-H), 4.00 (s, 3H, ArOCH3), 3.98 (s, 3H, ArOCH3),
3.55 (s, 3H, COOCH3), 0.95 (s, 3H, 19-CH3), 0.79 (d, J = 6.4 Hz, 3H,
21-CH3), 0.75 (s, 3H, 18-CH3); ESI-MS m/z (%): 873 [(M+1)+, 100].
Anal. Calcd for C45H56N6O8S2: C, 61.90; H, 6.46; N, 9.63. Found: C,
61.98; H, 6.47; N, 9.66%.
obtained was purified by column chromatography over silica gel H
using dichloromethane-ethyl acetate as the eluant to provide the
corresponding compounds 6.
This work was supported by the Science and Technology
Department of Si Chuan Province (No.2011JY0035), the
FundamentalResearchFundsforCentralUniversity, Southwest
University for Nationalities (No.11NZYTH05) and the Project
of Postgraduate Degree Point Construction, Southwest
University for Nationalities (No.2011XWD-S0703).
Received 14 February 2012; accepted 18 February 2012
Paper 1201163 doi: 10.3184/174751912X13319206588494
Published online: 17 April 2012
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