Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues

Article abstract of DOI:10.1080/15257770.2015.1114124

Several O-and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K₂CO₃ followed by deacetylation with Et₃N/H₂O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O-and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et₃N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, ¹H, ¹³C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.

Full text of DOI:10.1080/15257770.2015.1114124

Nucleosides, Nucleotides and Nucleic Acids
ISSN: 1525-7770 (Print) 1532-2335 (Online) Journal homepage: http://www.tandfonline.com/loi/lncn20
Synthesis and Biological Evaluation of 2-Oxo/
Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-
Based Nucleoside Analogues
Hassan A. El-Sayed, Said A. Said, Ahmed H. Moustafa, Mohamed M. Baraka &
Rimaa T. Abdel-Kader
To cite this article: Hassan A. El-Sayed, Said A. Said, Ahmed H. Moustafa, Mohamed M. Baraka
&
Rimaa T. Abdel-Kader (2016): Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline
and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues, Nucleosides, Nucleotides and
Nucleic Acids, DOI: 10.1080/15257770.2015.1114124
To link to this article: http://dx.doi.org/10.1080/15257770.2015.1114124
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Date: 26 January 2016, At: 07:07

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
http://dx.doi.org/./..
Synthesis and Biological Evaluation of -Oxo/
Thioxoquinoxaline and -Oxo/Thioxoquinoxaline-Based
Nucleoside Analogues
a
a
a
b
Hassan A. El-Sayed , Said A. Said , Ahmed H. Moustafa , Mohamed M. Baraka , and
a
Rimaa T. Abdel-Kader
a
b
Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt; Department of
Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
ABSTRACT
ARTICLE HISTORY
Several O- and S-quinoxaline glycosides have been prepared by
glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines
Received  February 
Accepted  October 
1
a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-
KEYWORDS
D-lactosyl bromide in the presence of K CO followed by
2
3
-Oxo(thioxo)quinoxaline;
cyclic/acyclic nucleosides;
sulfonamide; biological
evaluation
deacetylation with Et N/H O. Furthermore, alkylation of 1a,b
3
2
with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide,
and 3-chloropropanol afforded the corresponding O- and S-
acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic
acid followed by condensation with sulfacetamide and sulfadi-
azine in the presence of Et N/THF and ethyl chloroformate gave
3
the corresponding sulfonamide derivatives 14 and 15, respec-
tively. The structures of new compounds were confirmed by
1
13
using IR, H, C NMR spectra and microanalysis. Some of these
compounds were screened in vitro for antitumor and antifungal
activities.
Introduction
Quinoxaline is an important nitrogen-containing heterocyclic compound contain-
ing a ring complex made up of benzene and pyrazine rings. For example, quinox-
aline is a part of various antibiotics such as echinomycin, levomycin, and actino-
[
1,2]
lutin that are known to inhibit growth of gram-positive bacteria.
Derivatives
[
3–9]
of quinoxaline have different pharmacological activities such as antibacterial,
[
10,11]
[12]
[13,14]
[15,16]
antifungal,
antiviral,
antineoplastic,
antidepressant,
anticon-
[
17]
[18,19]
and antithrombotic,[20] NMDA antagonis-
vulsant,
anti-inflammatory,
[
21]
[22]
antimalarial,[23] antituberculosis,
[24,25]
tic,
antiglucoma,
and anti-HIV
[
26]
activities.
In addition, quinoxaline compounds possess intrinsic diuretic, utero-
tonic, hypertensive, and phosphodiesterase inhibitor activity. These are also used
in agricultural field as herbicides, fungicides, and insecticides. In addition, quinox-
aline derivatives are also useful in the formation of dyes, efficient electron
CONTACT Hassan A. El-Sayed
University, Zagazig, Egypt
hasanneg@gmail.com
Department of Chemistry, Faculty of Science, Zagazig
©
 Taylor & Francis Group, LLC

2
H. A. EL-SAYED ET AL.
luminescent materials, organic semiconductor, cavitands, and dehydoannu-
[
27–29]
lenes.
3-Methyl-2(1H)-quinoxalinones have been postulated as important
[
30–33]
intermediates for the synthesis of various useful heterocyclic compounds.
Hence, preparation of 3-methyl-2(1H)-quinoxalinones has attracted consider-
able attention in recent years. These compounds are generally prepared by
the condensation of o-phenylenediamine with pyruvic acid, but multiple by-
products are obtained when asymmetrical diamines were used as starting
[
34]
materials.
In addition, these compounds can also be obtained by some
[
35–37]
other regioselective methods.
Continuing our search for nucleosides
we wish to report the synthesis of 3-methyl-
(1H)quinoxalinone/thione (1a,b) and their O- and S-cyclic/acyclic nucleosides.
[
38–40]
with biological activities,
2
Results and discussion
Chemistry
3-Methyl-2(1H)quinoxalinone/thione (1a,b) (Scheme 1) were synthesized by the
reaction of o-phenylenediamine with sodium pyruvate in water according to the
[
32,41]
procedure given in literature.
Analyses are reported in the experimental sec-
tion due to the difference in melting points. Compounds 1a,b were obtained as
an amido tautomer as suggested by the presence of bands in IR spectra char-
acteristic for NH and C=O/C=S of amide/thioamide functional groups. Com-
pounds 1a,b were coupled with different organohalide compounds in the presence
of K CO in dry N,N-dimethylformaide (DMF) to give amide nucleoside analogues
2
3
(
Scheme 1).
Deacetylation with triethylamine (TEA) in H O/MeOH was effective if these
2
coupling agents gave O-acetylated products. Products before and after deacety-
lation were purified by recrystallization with ethanol. Structures of these sep-
arated coupling products were confirmed by IR, NMR, and elemental analy-
sis. Compounds 1a,b were coupled with peracetylated α-D-glucopyranosyl, α-D-
galactopyranosyl, and α-D-lactosyl bromide, leading to the formation of the cor-
responding O- and S-glycosides 2a,b, 4a,b, and 6a,b, respectively. The deacety-
lation of these glycosides gave the deacetylated products 3a,b, 5a,b, and 7a,b,
respectively. In all these compounds, the acetylated O-β-glycosides were obtained
in yields ranging from 59–86%. Formation of the O- and S-glycosides was con-
firmed by IR bands, which revealed the absence of amidic C=O and C=S
−
1
functional groups at 1665 and 1326 cm for each compound. These result-
1
ing nucleosides have a β-configuration as indicated by the H NMR cou-
pling constant of anomeric protons (J > 7.5 Hz) due to diaxial coupling with
ꢀ
H-2 .
The acyclic nucleosides analogue were synthesized by the coupling of 1a,b
with three different substituted alkyl halides (Scheme 1) (namely 4-bromobutyl
[
42]
[43]
acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol) to give, after
deprotection, the O- and S-alkylation products 9a,b, 11a,b, and 12a, respectively, in

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
3
Scheme The cyclic and acylic nucleosides of quinoxaline derivatives (1a,b). Reaction conditions and
reagents: (a), (b), and (c) Glucosyl/galactosyl and lactosyl bromode, K CO , dry DMF ( h), r.t. (d) -


bromobutyl acetate, -acetoxyethoxymethyl bromide, and -chloropropanol, K CO , dry DMF ( h),


r.t. (e) MeOH/Et N and few drops of water ( h), r.t.

good yields (Scheme 1). The products lacked the IR bands corresponding to the
amide C=O and C=S functional groups in contrast to the results that we observed
[
44]
in our previous work.
Other published work showed that a 2-oxoquinoxaline
structure is also glycosylated at the 2-oxo or 2-thioxo position under the same
[
45]
conditions. Furthermore, similar 2-oxoquinoxaline compound was also reported
to couple with ethyl bromoacetate at the 2-oxo position under reaction conditions
[
46]
similar to those used in our work.
Compound 13 was obtained from the alky-
lation of 3-methyl-2(1H)-quinoxalinethione (1b) using chloroacetic acid in reflux-
[
47]
ing ethanolic KOH
spectrum and chemical properties due to the free-COOH group making compound
3 soluble in alkaline solutions. Compound 13 was reacted with sulfacetamide
(Scheme 2). The chemical structure was confirmed by IR
1

4
H. A. EL-SAYED ET AL.
and sulfadiazine in tetrahydrofuran (THF), triethylamine (TEA), and ethyl chlo-
roformate, leading to compounds 14 and 15 in good yields (>80%) respectively
(
Scheme 2).
The structures of 14 and 15 were confirmed by IR, H NMR, mass spectroscopy,
and elemental analyses. The IR spectrum of 14 displayed bands at 3423, 3356, 1729,
1
−
1
and 1651 cm characteristic for 2NH and 2C=O functional groups, respectively.
+
1
The mass spectrum showed a parent ion peak at m/e (M ) = 430 (3.19%). H NMR
spectrum for compound 15 showed signals at δ 2.63 and 4.14 ppm characteristic
for CH and SCH CO, respectively, in addition to signal at δ 10.24 ppm for two
3
2
+
NH protons. The mass spectrum showed a parent ion at m/e (M ) = 367 (2.25%).
The elemental analyses of compounds 14 and 15 are in agreement with the assigned
structure.
Biology
Evaluation of antitumor activities
Cytotoxic activity. The cytotoxic effects of the prepared compounds (2b, 5a, 7a,
8
b, 11a, 14, and 15) were assessed toward hepatocellular carcinoma (HEPG-2) and
Scheme  Sulfonamide derivatives of quinoxaline 1a,b. Reaction conditions and reagents: (a)
Chloroacetic acid, EtOH, KOH, reflux ( h). (b) Sulfacetamide, THF, Et N, ethylchloroflormate, r.t. ( h).

(
c) Sulfadiazine, THF, Et N, ethylchloroformate, r.t. ( h).


NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
5
Table . Cytotoxicactivityofthepreparedcompounds(1–7)towardHEPG-andAtumorcelllines.
IC (µg/mL)
Sample
Compound
HEPG-
A

2b
5a
7a
8b
11a
4
.
.
.
.
.
.
.
.
.
.






.
.
.
.
5
(
A549) cell lines, using MTT as assay.[48] After 24-h growth of cells on 96 micro-
titer plates, under standard growth conditions, various concentrations of each com-
pound (10–100 µg/mL) were added to wells of monolayer cells incubated for 48 h at
3
7°C in a 5% CO incubator. After incubation, the cells were stained with the MTT
2
reagent, washed with 70% ethanol, and the developed color was measured by an
ELISA Reader at 570 nm. The assay was based on the ability of active mitochondrial
dehydrogenase of living tumor cells to cleave the tetrazolium ring of yellow MTT,
forming dark blue insoluble formazan crystals. After solubilization of crystals, the
number of viable cells was expressed by the development of dark blue color of solu-
ble formazan at 570 nm. The relative cell viability was calculated by the the following
equation:
ꢀ
ꢁ
[
A570 of sample]/[A570 of control] × 100.
From the profile of cytotoxic activity (Table 1 and Figure 1), compounds 5a and
a displayed the highest cytotoxic activity toward A549 cells (IC 56 µg/mL, IC
7
50
50
23 µg/mL) and HEPG-2 (IC50 59 µg/mL and IC50 38 µg/mL) respectively. Com-
pounds 11a and 14 exhibit a weak anti-proliferative activity toward A549 cells (IC50
2 µg/mL and IC50 57 µg/mL) and HEPG-2 cells (IC50 66 µg/mL and IC50 78
6
µg/mL), respectively. However, compounds2b, 8b, and 15 have little cytotoxic activ-
ity toward A549 as revealed from the values of half-inhibitory concentrations (IC ),
50
162, 112, and 182 µg/mL, respectively. The tumor cell line A549 was more vulnera-
ble to all the prepared compounds, compared with the relative resistance of HEPG-2
cells.
Figure . Cytotoxic activity of the prepared compounds (1–7) toward HEPG- and A tumor cell
lines.

6
H. A. EL-SAYED ET AL.
Table . Antimicrobial activity of prepared compounds against Bacillus subtilis and Aspergillus
carneus.
Diameter of inhibition zone (cm)
Compound
Aspergillus carneus
Bacillus subtilis
2
2
3
3
4
4
a
b
a
b
.
.
.






.

.


.
a
.
.
.
.
.
.
.
.
.
b
5
5
a
b
7
7
a
b
1
2a


4
5


Evaluation of antimicrobial activities
The concentration of tested compounds was 0.05 g/10 mL dissolved in DMF. The
DMF was used as a negative control for the tested fungal isolate. The antimicrobial
activity of the prepared compounds (2a,b, 3a,b, 4a,b, 5a,b, 7a,b, 12a, 14, and 15)
[
49]
was assessed by the cup diffusion method. Standard Dox’s agar medium was pre-
pared, and prior to solidification, the medium was seeded with the spore suspension
of Aspergillus carneus. After incubation of plates for 5 h, holes were made on each
plate, injected under aseptic conditions with 500 μL of tested compounds, dissolved
in DMSO, against negative control of DMSO solution. The plate cultures were incu-
bated at 30°C for five days, and the development of the inhibition growth zones was
observed daily.
From the growth profile of bacterial isolate, A. carneus, all the prepared com-
pounds have a relative antimicrobial activity with obvious fluctuation. From the
antifungal profile (Table 2), compound 5a has the maximum antifungal activity, fol-
lowed by compound 4b, with similar activity of compounds 3a and 3b among the
experimented compounds. However, the other synthesized compounds (2a, 2b, 4a,
5
b, 7b, 12a, 14, and 15) displayed a fairly inhibitory effect on the viability of tested
fungal isolate.
Conclusions
In summary, we have described the synthesis of some O- and S-cyclic and acyclic
quinoxaline nucleosides via alkylation of quinoxalines 1a,b with glucosyl, galac-
tosyl, and lactosyl bromide and acyclic alkylating agents; in addition, quinoxaline
sulfonamide derivatives were synthesized. The in vitro growth inhibitory activi-
ties of some new synthesized nucleosides against A549 and HEPG-2 tumor cell
lines revealed modest cytotoxic activity, with the most potential compounds being
5
a and 7a. In addition, compounds 3a,b, 4b, 5a, and 7a showed moderate activ-
ity against Aspergillus carneus, while no activity was observed against Bacillus
subtilis.

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
7
Experimental
All melting points were uncorrected and measured using an electro thermal IA 9100
apparatus. The IR spectra (KBr discs) were recorded on a Pye Unicam Sp-3–300
or a Shimadzu FTIR 8101 PC infrared spectrophotometer (Cairo University, Cairo,
1
13
Egypt). The operation frequency was 300 MHz for H and 75.5 MHz for C NMR
using JOEL-JNM-LA 300-MHz spectrometer. The coupling constants (J) are given
in hertz. The chemical shifts are expressed on δ (ppm) scale using TMS as a standard
reference. Biological evaluations were carried by holding company for Biological
Products and Vaccines (Vacsera), Giza, Cairo, Egypt, and the Microbiology Labo-
ratory, Faculty of Science, Zagazig University, Zagazig, Egypt. Elemental analyses
were determined on a Perkin Elmer 240 (Microanalysis Center, Cairo University,
Egypt).
General procedure for synthesis of compound (1a)
o-Phenylenediamine (5.4 g, 0.5 mol) was dissolved in warm water (60 mL); then was
added sodium pyruvate (5.6 g, 0.5 mol) in water (20 mL) portion-wise; after stirring
for 1 h, the mixture was acidified with dilute HCl to pH 3. Crystals were separated
and collected by filtration and recrystallized from hot water.
General procedure for synthesis of compound (1b)
A mixture of 3-methyl-2-(1H)-quinoxalinone (1a) (0.01 mol) and P S (0.01 mol)
2
5
was refluxed in dry pyridine (20 mL) for 5 h. The solvent was evaporated and the
residue was treated with dilute acetic acid. The solid product was removed by filtra-
tion and crystallized from absolute ethanol to give (1b).
General procedure for alkylation
In separate experiments, a mixture of 1a (10 mmol) and potassium carbonate (11
mmol) in dry DMF (15 mL) was stirred for 1 h, and halide (glucosyl bromide, galac-
tosyl bromide, lactosyl bromide, 4-bromobutylacetate, 2-acetoxyethoxymethyl bro-
mide, or 3-chloropropanol (11 mmol)) was added portion-wise to the well-stirred
reaction mixture. Stirring was continued overnight at room temperature. The sol-
vent was evaporated, and the residue was washed with water, and treated with
ethanol. The obtained precipitate was collected by filtration and recrystallized from
ethanol. Similar experiments were carried out with 1b.
General procedure for deacetylation of 2a,b, 4a,b, 6a,b, 8a,b, and 9a,b
A mixture of the compound (10 mmol) in methanol (20 mL), triethylamine (1
mL), and few drops of water was stirred for 6 h at room temperature, and then
the solvent was removed under reduced pressure. The residue was crystallized from
ethanol.

8
H. A. EL-SAYED ET AL.
-((-Methylquinoxalin--yl)thio)acetic acid (13)
A solution of 1b (14.7 mmol) in ethanol (30 mL), KOH (14.7 mmol), and
chloroacetic acid (14.7 mmol) was refluxed for 2 h. The hot mixture was filtered
and the ethanolic solution was evaporated under reduced pressure. The residue was
dissolved in distilled water and acidified with diluted HCl to pH 3. The precipitate
was collected by filtration, washed with cold distilled water, and dried in an oven at
40–45°C to provide (13), which was recrystallized from ethanol.
General procedure for preparing 14 and 15
An anhydrous solution of 13 (11.4 mmol) and TEA (11.4 mmol) in THF (30
mL) was cooled to 0–5°C. To this solution, an aliquot of ethylchloroformate (11.4
mmol) was added drop-wise with continuous stirring. The resulting mixture was
left for 30 min, with continuous stirring at 0–5°C. A cold aqueous solution (10
mL) of sulfadiazine or sulfacetamide (11.4 mmol) and TEA (11.4 mmol) was added
to the above mixture. The final mixture was vigorously stirred for 2 h at room
temperature, diluted with water (30 mL), and was extracted with diethyl ether
(
2 × 20 mL). The aqueous phase was acidified with diluted HCl to pH = 3,
and extracted with ethyl acetate (3 × 20 mL). The extracts were pooled together,
dried over anhydrous sodium sulfate, and evaporated under reduced pressure.
The residue was treated with petroleum ether (60/80), the precipitated product
was collected, dried, and recrystallized from ethanol to give 14 and 15 in good
yields.

-Methylquinoxalin-(H)-one (1a)
[
32]
−1
Colorless crystals; yield 85%, m.p. 238–240°C [lit. 245°C].
IR (KBr): 3433 cm
−
1
1
(
7
NH) and 1665 cm (C=O, amide). H NMR (DMSO-d ): δ = 2.59 (s, 3H, CH ),
6
3
.26 (m, 2H, Ar-H), 7.46 (d, 1H, J = 7.2 Hz, Ar-H), 7.70 (d, 1H, J = 8.4 Hz, Ar-H),
1
2.26 (s, 1H, NH). Anal. Calcd. for C H N O (159.16): C, 67.91; H, 4.43; N, 17.60.
9
8
2
Found: C, 67.94; H, 4.45; N, 17.56.

-Methylquinoxaline-(H)-thione (1b)
[
32]
Orange-brown crystals; yield 86%, m.p. 229–230°C [lit. 250–251°C].
IR (KBr):
−
1
−1
1
3
428 cm (NH) and 1326 cm (C=S). H NMR (DMSO-d ): δ = 2.59 (s, 3H,
6
CH ), 7.26 (m, 2H, Ar-H), 7.43 (d, 1H, J = 7.5 Hz, Ar-H), 7.70 (d, 1H, J = 8.45 Hz,
3
Ar-H), 12.26 (s, 1H, NH). Anal. Calcd. for C H N S (176.24): C, 61.34; H, 4.58; N,
9
8
2
15.90. Found: C, 61.28; H, 4.62; N, 15.87.
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-glucopyranosyloxy)--methyl- quinoxaline (2a)
−
1
Colorless crystals; yield 62%, m.p. 138–140°C. IR (KBr): 1757 and 1730 cm (C=O,
1
acetoxy). H NMR (DMSO-d ): δ = 1.96, 1.98, 2.02, and 2.05 (4 s, 12H, 4CH CO),
6
3
ꢀ
2
J5
.59 (s, 3H, CH ), 4.03 (dd, 1H, J
ꢀ
ꢀ
= 4.63, J
ꢀ
ꢀꢀ = 12.16 Hz, H-6 ), 4.10 (dd, 1H,
3
5 ,6
6 ,6
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ = 4.81, J
ꢀ
ꢀꢀ = 12.16 Hz, H-6 ), 4.25 (m, 1H, H-5 ), 5.03 (t, 1H, J
ꢀ
ꢀ
= 9.56
,6
6 ,6
3 ,4
ꢀ
ꢀ
ꢀ
Hz, H-4 ), 5.22 (t, 1H, J
ꢀ
ꢀ
= 9.30 Hz, H-2 ), 5.53 (t, 1H, J
ꢀ
ꢀ
= 9.30 Hz, H-3 ), 6.21
1
,2
2 ,3
13
ꢀ
(
d, 1H, J1
ꢀ
ꢀ
= 10.5 Hz, H-1 ), 7.76–8.01 (m, 4H, Ar-H). C NMR (DMSO-d6, δ
,2

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
9
ꢀ
ppm): 19.8, 20.0, 20.1, 21.1 (4CH , CH CO) 33.8 (CH -quinoxaline), 62.20 (C-6 ),
6
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
5.1 (C-4 ), 66.13 (C-3 ), 68.8 (C-2 ), 71.23 (C-5 ), 94.10 (C-1 ), 126.8, 128.5, 128.9,
1
29.2, 134.9, 157.1, 160.1, 161.2, 169.1, 169.9, 170.2, and 171.5 (Ar-C and C=O).
Anal. Calcd. for C H N O (490.46): C, 56.32; H, 5.34; N, 5.71. Found: C, 56.29;
23
26
2
10
H, 5.39; N, 5.75.
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-glucopyranosylsulfanyl)
-
-methyl- quinoxaline (2b)
−
1
Colorless crystals; yield 60%, m.p. 158–160°C. IR (KBr): 1753 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.78, 1.98, 2.01, and 2.02 (4s, 12H, 4CH CO), 2.59 (s, 3H,
6
3
ꢀ
CH ), 4.01 (dd, 1H, J
J6
(
1
ꢀ
ꢀ
= 4.65, J
ꢀ
ꢀꢀ = 12.15 Hz, H-6 ), 4.10 (dd, 1H, J
ꢀ
ꢀꢀ = 4.80,
3
5 ,6
6 ,6
5 ,6
ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ = 12.15 Hz, H-6 ), 4.26 (m, 1H, H-5 ), 5.03 (t, 1H, J
ꢀ
ꢀ
= 9.58 Hz, H-4 ), 5.22
,6
3 ,4
ꢀ
ꢀ
t, 1H, J
ꢀ
ꢀ
= 10.2 Hz, H-2 ), 5.54 (t, 1H, J
ꢀ
ꢀ
= 9.0 Hz, H-3 ), 6.21 (d, 1H, J
ꢀ
ꢀ
=
1
,2
2 ,3
1 ,2
ꢀ
0.5 Hz, H-1 ), 7.74–8.01 (m, 4H, Ar-H). Anal. Calcd. for C H N O S (506.53):
2
3
26
2
9
C, 54.54; H, 5.17; N, 5.53. Found: C, 54.51; H, 5.20; N, 5.56.
-(β-D-glucopyranosyloxy)--methylquinoxaline (3a)

−
ꢀ
1
Colorless crystals; yield 82%, m.p. 188–190°C. IR (KBr): 3427 cm (broad, 4OH).
1
ꢀꢀ
ꢀ
H NMR (DMSO-d ): δ = 2.49 (s, 3H, CH ), 3.18 (m, 6H, H-6 , H-6 , H-5 , H-
6
3
ꢀ
ꢀ
ꢀ
ꢀ
4
1
, H-3 and H-2 ), 3.47 (t, 1H, J = 5.64 Hz, OH-6 , D O exchangeable), 4.05 (t,
2
ꢀ
ꢀ
H, J = 6.60 Hz, OH-4 , D O exchangeable), 4.39 (t, 1H, J = 5.83 Hz, OH-3 , D O
2
2
ꢀ
exchangeable), 4.80 (t, 1H, J = 4.96 Hz, OH-2 , D O exchangeable), 5.78 (d, 1H, J
2
ꢀ
=
9.93 Hz, H-1 ), 7.28 (m, 2H, Ar-H), 7.46 (d, 1H, J = 7.2 Hz, Ar-H), 7.70 (d, 1H, J
=
8.4 Hz, Ar-H). Anal. Calcd. for C H N O (322.31): C, 55.90; H, 5.63; N, 8.69.
15
18
2
6
Found: C, 55.94; H, 5.61; N, 8.65.

-(β-D-glucopyranosylsulfanyl)--methylquinoxaline (3b)
−
1
Colorless crystals; yield 84%, m.p. 194–196°C. IR (KBr): 3364 cm (broad, 4OH).
1
ꢀ
ꢀꢀ
ꢀ
H NMR (DMSO-d ): δ = 2.59 (s, 3H, CH ), 3.21–3.61 (m, 6H, H-6 , H-6 , H-5 ,
6
ꢀ
3
ꢀ
ꢀ
ꢀ
H-4 , H-3 , and H-2 ), 5.65 (d, 1H, J = 9.30 Hz, H-1 ), 7.28–7.90 (m, 4H, Ar-H).
Anal. Calcd. for C H N O S (338.38): C, 53.24; H, 5.36; N, 8.28. Found: C, 53.21;
15
18
2
5
H, 5.38; N, 8.31.
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-galactopyranosyloxy)--methyl- quinoxaline (4a)
−
1
Colorless crystals; yield 65%, m.p. 160–162°C. IR (KBr): 1747 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.94, 1.96, 1.97, and 2.17 (4s, 12H, 4CH CO), 2.59 (s, 3H,
6
3
ꢀ
CH ), 4.07 (dd, 1H, J
ꢀ
ꢀ
= 6.21, J
ꢀ
ꢀꢀ = 11.96 Hz, H-6 ), 4.10 (dd, 1H, J
ꢀ
ꢀꢀ = 6.43,
3
5 ,6
6 ,6
5 ,6
ꢀ
ꢀ
ꢀ
ꢀ
J6
ꢀ
ꢀꢀ = 11.96 Hz, H-6 ), 4.57 (m, 1H, H-5 ), 5.36 (dd, 1H, J
ꢀ
ꢀ
= 8.23, J
ꢀ
= 2.50
,6
3 ,2
3 ,4
ꢀ
ꢀ
Hz, H-3 ), 5.39 (dd, 1H, J
ꢀ
ꢀ
= 8.10, J
ꢀ
ꢀ
= 8.23 Hz, H-2 ), 5.49 (dd, 1H, J
ꢀ
ꢀ
=
1
,2
2 ,3
3 ,4
ꢀ
ꢀ
2
.50, J4
ꢀ
ꢀ
= 3.60 Hz, H-4 ), 6.43 (d, 1H, J = 8.10 Hz, H-1 ), 7.69–7.95 (m, 4H, Ar-
,5
H). Anal. Calcd. for C H N O (490.46): C, 56.32; H, 5.34; N, 5.71. Found: C,
23
26
2
10
56.35; H, 5.36; N, 5.68.

1
0
H. A. EL-SAYED ET AL.
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-galactopyranosylsulfanyl)
-
-methyl-quinoxaline (4b)
−
1
Colorless crystals; yield 62%, m.p. 160–163°C. IR (KBr): 1751 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.75, 1.96, 2.01, and 2.13 (4s, 12H, 4CH CO), 2.59 (s, 3H,
6
3
ꢀ
CH ), 3.95 (dd, 1H, J
J6
Hz, H-3 ), 5.41 (dd, 1H, J
J4
H). C NMR (DMSO-d6, δ ppm): 20.08, 20.11, 20.23, 20.64 (4CH , CH CO) 33.4
(
7
ꢀ
ꢀ
= 6.25, J
ꢀ
ꢀꢀ = 12.10 Hz, H-6 ), 4.03 (dd, 1H, J
ꢀ
ꢀꢀ = 5.10,
3
5 ,6
ꢀ
6 ,6
5 ,6
ꢀ
ꢀ
ꢀ
ꢀꢀ = 12.10 Hz, H-6 ), 4.51 (m, 1H, H-5 ), 5.34 (dd, 1H, J
ꢀ
ꢀ
= 8.96, J
ꢀ
ꢀ
= 3.9
= 3.9,
,6
2 ,3
3 ,4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
= 10.8, J
ꢀ
ꢀ
= 8.96 Hz, H-2 ), 5.49 (t, 1H, J
ꢀ
ꢀ
1
,2
2 ,3
ꢀ
3 ,4
ꢀ
ꢀ
ꢀ
= 3.6 Hz, H-4 ), 6.16 (d, 1H, J
ꢀ
= 10.8 Hz, H-1 ), 7.73–7.99 (m, 4H, Ar-
,5
1 ,2
1
3
3
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
CH -quinoxaline), 60.6 (C-6 ), 66.12 (C-4 ), 68.2 (C-2 ), 71.0 (C-3 ), 72.2 (C-5 ),
3
ꢀ
9.2 (C-1 ), 126.2, 128.4, 128.8, 129.1, 135.1, 156.1, 160.1, 161.1, 168.8, 169.9, 170.0,
1
71.6 (Ar-C and C=O). Anal. Calcd. for C H N O S (506.53): C, 54.54; H, 5.17;
23
26
2
9
N, 5.53. Found: C, 54.58; H, 5.15; N, 5.51.

-(β-D-Galactopyranosyloxy)--methylquinoxaline (5a)
−
1
Colorless crystals; yield 85%, m.p. 179–180°C. IR (KBr): 3410 cm (broad, 4OH).
1
ꢀ
ꢀ
ꢀ
H NMR (DMSO-d ): δ = 2.59 (s, 3H, CH ), 3.57 (m, 3H, H-3 , H-6 , and H-6ꢀ ),
6
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
.63 (m, 3H, H-2 , H-4 , and H-5 ), 4.61 (m, 2H, OH-4 , OH-6 , D O exchangeable),
2
.92 (d, 1H, J = 5.13 Hz, OH-3 ), 5.21 (d, 1H, J = 4.2 Hz, OH-2 , D O exchange-
ꢀ
ꢀ
4
2
ꢀ
able), 6.03 (d, 1H, J = 7.8 Hz, H-1 ), 7.60–7.95 (m, 4H, Ar-H). Anal. Calcd. for
C H N O (322.31): C, 55.90; H, 5.63; N, 8.69. Found: C, 55.86; H, 5.60; N, 8.72.
15
18
2
6

-(β-D-Galactopyranosylsulfanyl)--methylquinoxaline (5b)
−
1
Colorless crystals; yield 86%, m.p. 189–190°C. IR (KBr): 3415 cm (broad, 4OH).
1
ꢀ
ꢀ
H NMR (DMSO-d /D O): δ = 2.59 (s, 3H, CH ), 3.38 (m, 3H, H-3 , H-6 , and H-
6
2
3
ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀ
6
), 3.59 (m, 3H, H-2 , H-4 , and H-5 ), 5.63 (d, 1H, J = 10.2 Hz, H-1 ), 7.25–7.93
(m, 4H, Ar-H). Anal. Calcd. for C H N O S (338.38): C, 53.24; H, 5.36; N, 8.28.
15 18 2 5
Found: C, 53.19; H, 5.33; N, 8.30.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-galactopyranosyl)-(→)-( , , -tri-O-acetyl-β-D-
glucopyranosyloxy)--methylquinoxaline (6a)
−
1
Brown powder; yield 59%, m.p. 191–192°C. IR (KBr): 1749 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.89, 1.90, 1.92, 1.94, 1.98, 2.00, and 2.10 (7s, 21H,
6
ꢀ
ꢀ
ꢀ
7
1
J 6ꢀꢀ
CH CO), 2.59 (s, 3H, CH ), 4.00–4.02 (m, 3H, H-2 b, H-6 a and H-6 b), 4.18 (dd,
3
3
ꢀꢀ
ꢀ
H, J ꢀꢀ
ꢀ
= 11.49, J
ꢀ
ꢀꢀ = 5.61 Hz, H-6 a), 4.28 (m, 1H, H-5 b), 4.73 (dd, 1H,
6
a,6 a
5 a,6 a
ꢀ
ꢀ
ꢀ
ꢀ
= 6.32 Hz, H-6 b), 4.86 (m, 1H, H-5 a), 4.95 (dd, 1H, J
ꢀ
ꢀ
= 7.86 Hz,
b,5 b
1 b,2 b
ꢀ
ꢀ
H-1 b), 5.13 (dd, 1H, J
ꢀ
ꢀ
= 3.4, J
ꢀ
ꢀ
= 3.8 Hz, H-4 b), 5.21 (dd, 1H, J
ꢀ
ꢀ
=
4
b,3 b
4 b,5 b
2 a,1 a
ꢀ
ꢀ
8
5
.97, J 2
ꢀ
ꢀ
= 8.40 Hz, H-2 a), 5.25 (dd, 1H, J
ꢀ
ꢀ
= 9.15, J
ꢀ
ꢀ
= 9.60 Hz, H-4 a),
a,3 a
3 a,4 a
4 a,5 a
ꢀ
.36 (d, 1H, J 3
ꢀ
ꢀ
= 3.4 Hz, H-3 b), 5.42 (dd, 1H, J
ꢀ
ꢀ
= 8.40, J
ꢀ
ꢀ
= 9.15 Hz,
b,4 b
3 a,2 a
3 a,4 a
ꢀ
ꢀ
H-3 a), 6.46 (d, 1H, J1
ꢀ
ꢀ
= 8.97 Hz, H-1 a), 7.69–7.98 (m, 4H, Ar-H). Anal. Calcd.
a,2 a
for C H N O (778.71): C, 53.98; H, 5.44; N, 3.60. Found: C, 54.01; H, 5.42; N,
35
42
2
18
3.64.

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
11
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ

-( , , , -Tetra-O-acetyl-β-D-galactopyranosyl)-(→)-( , , -tri-O-acetyl-β-D-
glucopyranosylsulfanyl)--methylquinoxaline (6b)
−
1
Colorless powder; yield 62%, m.p 160–163°C, IR (KBr): 1755, 1724 cm (C=O,
1
acetoxy). H NMR (DMSO-d ): δ = 1.79, 1.80, 1.97, 2.00, 2.02, 2.32, and 2.34 (7s,
6
ꢀ
ꢀ
ꢀ
2
(
1
1H, 7 CH CO), 2.59 (s, 3H, CH ), 4.03–4.07 (m, 3H, H-2 b, H-6 a, and H-6 b), 4.2
3 3
ꢀ
ꢀ
ꢀ
dd, 1 H, J ꢀꢀ
ꢀ
= 11.40, J
ꢀ
ꢀꢀ = 5.75 Hz, H-6 a), 4.24 (m, 1H, H-5 b), 5.06 (dd,
6
a,6 a
5 a,6 a
ꢀꢀ
ꢀ
H, J ꢀꢀ
ꢀ
= 6.35 Hz, H-6 b), 5.11 (m, 1H, H-5 a), 5.14 (dd, 1H, J
ꢀ
ꢀ
= 7.96 Hz,
6
b,5 b
1 b,2 b
ꢀ
ꢀ
H-1 b), 5.17 (dd, 1H, J
ꢀ
ꢀ
= 3.23, J
ꢀ
ꢀ
= 3.74 Hz, H-4 b), 5.24 (dd, 1H, J
ꢀ
ꢀ
=
4
b,3 b
4 b,5 b
2 a,1 a
ꢀ
ꢀ
8
5
.94, J 2
ꢀ
ꢀ
= 8.10 Hz, H-2 a), 5.50 (dd, 1H, J
ꢀ
ꢀ
= 9.15, J
ꢀ
ꢀ
= 9.60 Hz, H-4 a),
a,3 a
3 a,4 a
4 a,5 a
ꢀ
.53 (d, 1H, J 3
ꢀ
ꢀ
= 3.23 Hz, H-3 b), 5.93 (dd, 1H, J
ꢀ
ꢀ
= 8.10, J
ꢀ
ꢀ
= 9.15 Hz,
b,4 b
3 a,2 a
3 a,4 a
ꢀ
ꢀ
13
H-3 a), 6.23 (d, 1H, J1
ꢀ
ꢀ
= 8.94 Hz, H-1 a), 7.55–7.92 (m, 4H, Ar-H). C NMR
a,2 a
(
3
(
1
1
(
DMSO-d6, δ ppm): 20.9, 21.0, 21.09, 21.1, 22.3, 22.5, 26.8 (7CH , acetyl groups)
3.6 (CH -quinoxaline), 60.7 (C-6 a), 61.3 (C-6 b), 68.1 (C-3 a), 68.9 (C-2 b), 71.0
C-2 a), 72.0 (C-3 b), 72.6 (C-4 a), 73.5 (C-4 b), 78.6 (C-5 b), 78.9 (C-5 a), 83.5 (C-
3
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
a), 94.6 (C-1 b), 126.7, 128.6, 129.3, 129.7, 135.6, 157.0, 159.2, 160.8, 169.5, 169.9,
70.2, 170.3, 170.6, 171.2, 171.5 (Ar-C) and C=O). Anal. Calcd. for C H N O S
35
42
2
17
794.78): C, 52.89; H, 5.33; N, 3.52. Found: C, 52.80; H, 5.32; N, 3.51.

-(β-D-galactopyranosyl)-(→)-(β-D-glucopyranosyloxy)--methyl-
quinoxaline (7a)
Brown crystals; yield 83%, m.p. 190–192°C, IR (KBr): 3433 cm (broad, 7 OH).
−
1
1
ꢀ
ꢀ
H NMR (DMSO-d ): δ = 2.59 (s, 3H, CH ), 3.04–3.52 (4 m, 12H, H-2 b, H-3 b,
6
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H-4 b, H-5 b, H-6 b, H-6“b, H-2 a, H-3 a, H-4 a, H-5 a, H-6 a, H-6”a), 4.19 (d, 1H,
ꢀ
ꢀ
ꢀ
OH-4 b), 4.31 (d, 1H, OH-6 b), 4.63 (d, 1H, J = 4.28 Hz, OH-3 b), 4.89 (d, 1H, OH-
ꢀ
ꢀ
ꢀ
ꢀ
2
J1
b), 4.99 (d, 1H, OH-6 a), 5.21 (d, 1H, OH-3 a), 5.73 (d, 1H, OH-2 a), 5.82 (d, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
= 7.65 Hz, H-1 b), 6.10 (d, 1H, J
ꢀ
ꢀ
= 8.84 Hz, H-1 a), 7.3–7.95 (m, 4H,
b,2 b
1 a,2 a
Ar-H). Anal. Calcd. for C H N O (484.45): C, 52.06; H, 5.83; N, 5.78. Found: C,
21
28
2
11
52.04; H, 5.84; N, 5.79.

-(β-D-galactopyranosyl)-(→)-(β-D-glucopyranosylsulfanyl)--
methylquinoxaline (7b)
Colorless powder; yield 82%, m.p. 189–191°C, IR (KBr): 3443 cm (broad, 7 OH).
−
1
1
ꢀ
ꢀ
H NMR (DMSO-d ): δ = 2.56 (s, 3H, CH ), 3.01–3.62 (4 m, 12H, H-2 b, H-3 b,
6
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
H-4 b, H-5 b, H-6 b, H-6“b, H-2 a, H-3 a, H-4 a, H-5 a, H-6 a, H-6”a), 4.18 (d, 1H,
ꢀ
ꢀ
ꢀ
OH-4 b), 4.33 (d, 1H, OH-6 b), 4.60 (d, 1H, J = 4.28 Hz, OH-3 b), 4.87 (d, 1H, OH-
ꢀ
ꢀ
ꢀ
ꢀ
2
J1
b), 4.99 (d, 1H, OH-6 a), 5.20 (d, 1H, OH-3 a), 5.71 (d, 1H, OH-2 a), 5.84 (d, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
= 7.65 Hz, H-1 b), 6.12 (d, 1H, J
ꢀ
ꢀ
= 8.84 Hz, H-1 a), 7.32–7.95 (m, 4H,
b,2 b
1 a,2 a
Ar-H). Anal. Calcd. for C H N O S (500.52): C, 50.39; H, 5.64; N, 5.60. Found:
21
28
2
10
C, 50.37; H, 5.66; N, 5.58.

-(-Acetoxybutyloxy)--methylquinoxaline (8a)
−
1
Yellow powder; yield 55%, m.p. 110–112°C. IR (KBr): 1732 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.76 (m, 2H, CH ), 1.83 (m, 2H, CH ), 1.99 (s, 3H,
6
2
2
CH CO), 2.59 (s, 3H, CH ), 4.09 (t, 2H, J = 6.0 Hz, OCH ), 4.47 (t, 2H, J = 6.3
3
3
2

1
2
H. A. EL-SAYED ET AL.
Hz, CH OCO), 7.55–7.92 (m, 4H, Ar-H). Anal. Calcd. for C H N O (274.32):
2
15 18
2
3
C, 65.68; H, 6.61; N, 10.21. Found: C, 65.65; H, 6.59; N, 10.18.

-(-Acetoxybutylsulfanyl)--methylquinoxaline (8b)
−
1
Yellow powder; yield 55%, m.p. 130–133°C. IR (KBr): 1734 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.60 (m, 2H, CH ), 1.75 (m, 2H, CH ), 1.97 (s, 3H,
6
2
2
CH CO), 2.59 (s, 3H, CH ), 3.32 (t, 2H, J = 7.2 Hz, CH ), 3.45 (t, 2H, J = 6.0 Hz,
3
3
2
CH O), 7.65–7.93 (m, 4H, Ar-H). Anal. Calcd. for C H N O S (290.38): C, 62.04;
2
15 18
2
2
H, 6.25; N, 9.65. Found: C, 62.01; H, 6.27; N, 9.67.

-(-Hydroxybutyloxy)--methylquinoxaline (9a)
−
1
Colorless crystals; yield 65%, m.p. 150–152°C. IR (KBr): 3427 cm (broad, 4OH).
1
H NMR (DMSO-d ): δ = 1.58 (m, 2H, CH ), 1.81 (m, 2H, CH ), 2.59 (s, 3H, CH ),
6
2
2
3
3
.47 (q, 2H, J = 6.3 Hz, CH OH), 4.09 (t, 2H, J = 5.12 Hz, OCH ), 4.46 (t, 1H,
2
2
J = 5.4 Hz, OH, D O exchangeable), 7.53–7.90 (m, 4H, Ar-H). Anal. Calcd. for
2
C H N O (232.28): C, 67.22; H, 6.94; N, 12.06. Found: C, 67.25; H, 6.92; N, 12.03.
13
16
2
2

-(-Hydroxybutylsulfanyl)--methylquinoxaline (9b)
−
1
1
Colorless powder; yield 75%, m.p. 170°C, IR (KBr): 3426 cm (broad, OH). H
NMR (DMSO-d ): δ = 1.58 (m, 2H, CH ), 1.77(m, 2H, CH ), 2.59(s, 3H, CH ), 3.31
6
2
2
3
(
q, 2H, J = 6.6 Hz, SCH ), 3.47 (q, 2H, J = 6.0 Hz, CH OH), 4.43 (t, 1H, OH, D O
2
2
2
exchangeable), 7.65–7.93 (m, 4H, Ar-H). Anal. Calcd. for C H N OS (248.34): C,
13
16
2
62.87; H, 6.49; N, 11.28. Found: C, 62.85; H, 6.50; N, 11.26.

-[(-Acetoxyethoxy)methyoxy]--methylquinoxaline (10a)
−
1
Yellow powder; yield 50%, m.p. 150–152°C. IR (KBr): 17342 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 1.90 (s, 3H, CH CO), 2.59 (s, 3H, CH ), 3.78 (t, 2H, J =
6
3
3
5
.7 Hz, OCH ), 4.23 (t, 2H, J = 5.7 Hz, CH OCO), 4.43 (s, 2H, J = 7.2 Hz, OCH O),
2
2
2
7
.06–7.46 (m, 4H, Ar-H). Anal. Calcd. for C H N O (276.29): C, 60.86; H, 5.84;
14 16 2 4
N, 10.14. Found: C, 60.84; H, 5.85; N, 10.11.

-[(-Acetoxyethoxy)methylsulfanyl]--methylquinoxaline (10b)
−
1
Brown crystals; yield 60%, m.p. 160–162°C, IR (KBr): 1758 cm (C=O, acetoxy).
1
H NMR (DMSO-d ): δ = 2.02 (s, 3H, CH CO), 2.59 (s, 3H, CH ), 3.26 (s, 2H,
6
3
3
SCH O), 4.45 (t, 2H, J = 5.1 Hz, CH ), 4.71 (t, 2H, J = 5.1 Hz, CH ), 7.22–7.79
2
2
2
(
m, 4H, Ar-H). Anal. Calcd. for C H N O S (292.35): C, 57.52; H, 5.52; N, 9.58.
14 16 2 3
Found: C, 57.50; H, 5.54; N, 9.56.

-((-Hydroxyethoxy)methyloxy)--methylquinoxaline (11a)
Yellow crystals; yield 65%, m.p. 180–182°C, IR (KBr): 3443 cm (br, OH). H NMR
DMSO-d ): δ = 2.59 (s, 3H, CH ), 2.65 (t, 2H, J = 6.3 Hz, CH ), 3.31 (t, 1H, OH,
−
1
1
(
6
3
2
D O exchangeable) 3.79 (q, 2H, J = 7.2 Hz, CH OH), 6.39 (s, 2H, OCH O), 7.23–
2
2
2
7
.70 (m, 4H, Ar-H). Anal. Calcd. for C H N O (234.25): C, 61.53; H, 6.02; N,
12 14 2 3
11.96. Found: C, 61.51; H, 6.04; N, 11.94.

NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS
13

-((-Hydroxyethoxy)methylsulfanyl)--methylquinoxaline (11b)
−
1
1
Yellow crystals; yield 75%, m.p. 175–178°C, IR (KBr): 3350 cm (OH). H NMR
DMSO-d ): δ = 2.59 (s, 3H, CH ), 3.38 (s, 2H, SCH O), 3.84 (t, 2H, J = 5.4 Hz,
(
6
3
2
CH ), 4.64 (m, 2H, CH ), 5.82 (s, 1H, OH, D O exchangeable), 7.34–7.78 (m, 4H,
2
2
2
Ar-H). Anal. Calcd. for C H N O S (250.32): C, 57.58; H, 5.64; N, 11.19. Found:
12
14
2
2
C, 57.56; H, 5.62; N, 11.17.

-(-Methylquinoxalin--yloxy)propan--ol (12a)
1
Yellow crystals; yield 70%, m.p. 189–191°C. IR: 3441 (OH). H NMR (DMSO-d ): δ
6
=
=
1.71 (m, 2H, CH ), 2.59 (s, 3H, CH ), 2.65 (t, 2H, J = 6.3 Hz, OCH ), 3.31(t, 1H, J
2
3
2
5.4 Hz, OH, D O exchangeable), 3.79 (q, 2H, J = 6.9 Hz, CH -OH), 7.23–7.70 (m,
2
2
13
4
H, Ar-H). C NMR (DMSO-d6, δ ppm): 30.1 (CH ), 33.6 (CH OH), 33.7 (CH -
2
2
3
quinoxaline), 68.9 (OCH ), 126.8, 128.6, 128.5, 129.0, 135.0, 156.8, 160.1, 161.0 (Ar-
2
C). Anal. Calcd. for C H N O (218.25): C, 66.04; H, 6.47; N, 12.84. Found: C,
12
14
2
2
66.02; H, 6.49; N, 12.81.

-(-Methylquinoxalin--ythio)acetic acid (13)
−
1
Colorless crystals; yield 70%, m.p. 180–183°C. IR (KBr): 3480 cm (OH) and 1710
−
1
cm (C=O, acid). Anal. Calcd. for C H N O S (234.27): C, 56.39; H, 4.30; N,
11
10
2
2
1
1.96. Found: C, 56.37; H, 4.28; N,11.98.
N-(-(N-Acetylsulfamoyl)phenyl)--((-methylquinoxalin--yl)thio)-acetamide (14)
−
1
Yellow crystals; yield 82%, m.p. 166°C (decomposed). IR (KBr): 3423, 3356 cm
−
1
−1
(
2NH), 1726 cm (CH CONHSO ) and 1651 cm (CH CONH). Mass spectra:
3 2 2
+
M (m/e) = 430 (3.19%) as parent ion and m/e = 79.90 (100%), 63.90 (83.01%).
Anal. Calcd. for C H N O S (430.50): C, 53.01; H, 4.21; N, 13.01. Found: C,
19
18
4
4 2
53.00; H, 4.24; N, 13.04.
-(((-Methylquinoxalin--yl)thio)-N-(-(pyrimidin--yl)sulfamoyl)phenyl)
acetamide (15)
−
1
Yellow crystals; yield 85%, m.p. 176°C (decomposed). IR (KBr): 3435 br, cm
−
1
1
(
4
2NH), 1667 cm (C=O, amide). H NMR (DMSO-d ): δ = 2.63 (s, 3H, CH ),
6
3
.14 (s, 2H, SCH CO), 7.21 (s, 2H, Ar-H), 7.73 (m, 5H, Ar-H), 7.86 (d, 2H, J = 9.3
2
Hz, Ar-H), 7.96 (d, 2H, J = 9.3 Hz, Ar-H) and 10.24 (s, 2H, 2NH). Mass spectra:
+
M (m/e) = 367 (2.25%), m/e = 63.95 (69.26%), 79.95 (91.37%), 102.1 (54.18%),
1
43.05 (58.53%), 188.05 (50.78%), 189.05 (100%). Anal. Calcd. for C H N O S
21 18 6 3 2
(466.45): C, 54.06; H, 3.89; N, 18.01. Found: C, 54.09; H, 3.96; N, 18.04.
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