Synthesis of quinoxaline reverse ribofuranosides and their O-regioisomers

Article abstract of DOI:10.1007/s00706-014-1193-x

Six quinoxaline reverse nucleosides were prepared by reaction of quinoxalin-2-one derivatives with methyl 2,3-O-isopropylidene-5-O-p- toluenesulfonyl-β-d-ribofuranoside in the presence of sodium hydride. For deprotection of quinoxaline nucleosides, heatin

Full text of DOI:10.1007/s00706-014-1193-x

Monatsh Chem
DOI 10.1007/s00706-014-1193-x
ORIGINAL PAPER
Synthesis of quinoxaline reverse ribofuranosides
and their O-regioisomers
•
Ibrahim A. I. Ali Samir M. El Rayes
Received: 26 October 2013 / Accepted: 27 January 2014
Ó Springer-Verlag Wien 2014
Abstract Six quinoxaline reverse nucleosides were pre-
pared by reaction of quinoxalin-2-one derivatives with
methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-b-D-
ribofuranoside in the presence of sodium hydride. For
deprotection of quinoxaline nucleosides, heating in 60 %
acetic acid was applied. The novel compounds were
characterized by elemental analysis, mass spectra, and
NMR data.
bromide in the presence of NaH to give a mixture of O- and
N-allyl-substituted quinoxalines, a reaction we will apply
to prepare respective nucleosides.
Results and discussion
In view of these facts and in continuation of our efforts in
synthesizing various bioactive molecules [19–22], we have
found it desirable to synthesize a series of reverse
nucleosides whose chemical modifications include quin-
oxaline as the heterocyclic base and ribose as the sugar
moiety. The N-reverse nucleosides and the O-regioisomers
could be useful for the antiviral evaluation.
Keywords Reverse nucleosides ꢀ Quinoxaline ꢀ
Alkylation ꢀ Hydrolysis ꢀ Ribose
Introduction
Treatment of quinoxalines 1a–1f with protected methyl
2,3-O-isopropylidene-5-O-p-toluenesulfonyl-b-D-ribofur-
anoside (2) in the presence of NaH in N,N-
dimethylformamide always afforded a mixture of N- and
O-nucleoside quinoxaline derivatives 3a–3f and 4a–4f
(Scheme 1). The two N-reverse nucleosides and O-regio-
isomer were easily separated by column chromatography
using petroleum ether/ethyl-acetate (5:1) as eluent to afford
3a–3f in 57–64 % yield and 4a–4f in 19–26 % yield.
The structure assignment of the prepared N- and
O-substituted ribose derivatives 3a–3f and 4a–4f was based
on NMR and mass spectroscopy and physicochemical
analysis. The elemental analysis together with mass spectra
of N- and O-substituted ribose 3a–3f and 4a–4f gave
identical results that agreed with the molecular formula of
these compounds. This made us conclude that these com-
pounds are isomeric alkylated products (Scheme 2).
The mass spectra of 3a and 4a gave m/z = 332.0. The
1H and 13C NMR spectra of compounds 3a–3f and 4a–4f
provided evidence to deduce the site of alkylation. Thus,
The quinoxalines are a class of heterocyclic compounds
with different applications in various fields, whether
pharmacology [1, 2], agricultural chemistry [3, 4], or
chemical industry [5, 6]. The pharmacological applications
of quinoxalines are reported as angiotension II receptor
antagonists [7], N-methyl-D-aspartate (NMDA) antagonists
[8], anti-inflammatory [9], antidepressant-tranquilizing [10,
11], anti-tumor agents [12, 13], as well as agents against
hepatitis B virus (HBV) [14]. AG 1295 (Fig. 1), a quin-
oxaline derivative, has been shown to block EGFR kinase
selectively. This molecule has been shown to reverse the
transformed phenotype of sis-transformed NIH 3T3 cells
and slow C6 glioma-induced tumors in nude mice [15].
Recently, Ali and Fathalla [16–18] have reported the
regioselective alkylation of quinoxalines with allyl
I. A. I. Ali (&) ꢀ S. M. El Rayes
Department of Chemistry, Faculty of Science,
Suez Canal University, Ismailia, Egypt
e-mail: ibrahim3369@yahoo.com
1
the H NMR spectrum of 3d showed a multiplet signal at
123

I. A. I. Ali, S. M. El Rayes
d = 4.52–3.84 ppm attributed to NCH2 group. In addition,
an aromatic singlet signal in the region of 7.50 and
7.13 ppm and aliphatic signals at 5.04, 3.41, 2.45, and
2.30 ppm corresponding to b-H-1, OCH3, and 2 CH3
groups were found. The 13C NMR spectrum gave clear
evidence for the site of alkylation; thus, the 13C NMR of 3d
gave an interesting signal at d = 44.8 ppm typically
associated with NCH2 group, which is common for all
N-substituted quinoxaline derivatives 3a-3f. The 13C NMR
spectrum also showed signals at 110.0, 55.5, 25.6, and
24.0 ppm associated with (C-1), OCH3, and 2 CH3
(Scheme 3).
On the other hand, the 1H NMR spectrum of 4d exhibits
multiplet signals at d = 4.49–4.44 ppm associated with the
OCH2 group. The H NMR spectrum of 4d also shows
1
three signals at 5.02, 3.33, and 2.41 ppm corresponding to
b-H-1, OCH3, and 2 CH3. The 13C NMR spectrum of 3d
gave an interesting signal at d = 66.2 ppm typically
associated with OCH2 group, which is common for all
O-substituted quinoxaline derivatives 4a–4f. The 13C NMR
spectrum also showed signals at 109.1, 54.8, 26.3, and
24.9 ppm associated with (C-1), OCH3, and 2 CH3. All
NMR spectra of compounds 3a–3f and 4a–4f showed two
different NMR patterns in the aromatic region because of
an anisotropy caused by the adjacent alkyl substituent
Fig. 1 EGFR tyrosine kinase inhibitors
Scheme 1
123

Synthesis of quinoxaline reverse ribofuranosides
Scheme 2
toward both methyl groups and the aromatic protons in
case of N-substituted quinoxalines 3a–3f.
d = 4.58, 4.20–3.72, and 3.39 ppm corresponding to b-H-
1, NCH2, and OCH3, respectively. The 13C NMR spectrum
of 5d shows signals at d = 108.4, 45.2, and 44.5 ppm
attributed to (C-1), OCH3, and NCH2. The 1H NMR of the
7d appeared at 4.85, 4.38–4.21, and 3.32 ppm corre-
sponding to b-H-1, OCH2, and OCH3. The 13C NMR
spectrum of 4e shows signals at d = 108.3, 67.3, and
54.2 ppm attributed to (C-1), OCH2, and OCH3.
The free sugar residue of the reverse nucleosides could
be valuable for antiviral application purposes [23]. Thus,
treatment of quinoxaline N-nucleoside 3a–3f with 60 %
aqueous acetic acid at 80 °C monitored with TLC until
complete consumption of starting material gave com-
pounds 5a–5f and 6a–6f. This reaction condition showed
no selectivity leading to the removal of the isopropylidene
group 5a–5f as well as the removal of both protecting
groups (isopropylidene and OMe groups) of 6a–6f. We
further separated both products via column chromatogra-
phy. Compounds 5a–5f were completely hydrolyzed by
heating with 60 % acetic acid and gave 6a–6f. Also,
compounds 3a–3f were completely converted to 6a–6f
under the same reaction conditions by elongation of the
reaction time.
Conclusions
In conclusion, an efficient method for the syntheses of
various quinoxaline reverse nucleosides and their O-re-
gioisomers has been described in high yields as potential
chemotherapeutic agents.
1
The H NMR spectra of compounds 5a–5f gave evi-
dence of the removal of the isopropylidene in the presence
of OCH3 but in 6a–6f the signals of isopropylidene and
OCH3 disappeared.
Experimental
Solvents were purified and dried in the usual way. The
boiling range of the petroleum ether used was 40–60 °C.
Thin layer chromatography (TLC): silica gel 60 F254
plastic plates (E. Merck, layer thickness 0.2 mm) detected
by UV absorption. Melting points were determined on a
Bu¨chi 510 melting-point apparatus. NMR spectra were
measured with Bruker AC 250 (250 MHz) using TMS
(0.00 ppm) as internal standard. Mass spectra were
Similarly, deprotection of the quinoxaline O-nucleoside
4a–4f with 60 % acetic acid at reflux gave 7a–7f and 8a–8f
in good yields. The structures were confirmed by studying
1H and 13C NMR spectra.
The structure assignment of quinoxaline reverse
nucleosides 5d and 7d was based on spectral analysis
1
(Fig. 2). The H NMR spectrum of 5d exhibits signals at
123

I. A. I. Ali, S. M. El Rayes
Scheme 3
1
Fig. 2 Selected H NMR and 13C NMR spectral data of 3e and 4e
Preparation of compound 3a–3f and 4a–4f
measured on a GC-MSQP 1000EX Shimadzu. Elemental
analyses were performed on a Flash EA-1112 instrument at
the Microanalytical Laboratory, Faculty of Science, Suez
Canal University Ismailia, Egypt, and the results agreed
favorably with calculated values. The starting compounds
1a–1f [24, 25] and 2 [23, 26] were prepared according to
the methods described in the literature.
A mixture of quinoxaline 1a–1f (10.0 mmol) and 0.24 g
NaH (10.0 mmol) in 50 cm3 dry DMF was stirred at
100 °C for 1 h. The sugar derivative 2 (3.42 g, 10.0 mmol)
was added, and the mixture was stirred at 100 °C for 5 h.
The solution was evaporated to dryness. The residue was
123

Synthesis of quinoxaline reverse ribofuranosides
4.93 (d, 1H, J = 6.0 Hz, H-2), 5.04 (s, 1H, H-1), 7.13 (s,
1H, Ar–H), 7.50 (s, 1H, Ar–H), 8.22 (s, 1H, CH) ppm; 13C
NMR (62.5 MHz, CDCl3): d = 19.8 (CH3), 22.1 (CH3),
24.0 (CH3), 25.6 (CH3), 44.8 (C-5), 55.5 (OCH3), 82.1 (C-
4), 83.5 (C-3), 85.0 (C-2), 110.0 (C-1), 113.5 (C(CH3)2),
115.0, 129.5, 130.1, 132.0, 133.6, 142.4, 148.3 (Ar–C),
156.2 (CO) ppm.
purified by column chromatography petroleum ether/ethyl
acetate (5:1) as eluent to give 3a–3f and 4a–4f.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(2-oxo-1(2H)-
quinoxalinyl)-b-D-ribofuranoside (3a, C17H20N2O5)
White crystals (57 %); m.p.: 79–81 °C; 1H NMR
(250 MHz, CDCl3): d = 1.23 (s, 3H, CH3), 1.37 (s, 3H,
CH3), 3.40 (s, 3H, OCH3), 3.87–3.94 (m, 1H, H-50),
4.46–4.53 (m, 2H, H-4, H-5), 4.87–4.93 (m, 2H, H-2, H-3),
5.01 (s, 1H, H-1), 7.23–7.42 (m, 2H, Ar–H), 7.55–7.61 (m,
1H, Ar–H), 7.81–7.88 (m, 1H, Ar–H), 8.27 (s, 1H, CH)
ppm; 13C NMR (62.5 MHz, CDCl3): d = 24.8 (CH3), 26.2
(CH3), 44.2 (C-5), 55.3 (OCH3), 82.2 (C-4), 83.6 (C-3),
85.3 (C-2), 110.2 (C-1), 112.3 (C(CH3)2), 113.8, 123.9,
130.9, 131.1, 132.1, 133.6, 150.0 (Ar–C), 154.8 (CO) ppm;
MS: m/z (%) = 332.0.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(3,6,7-trimethyl-2-
oxo-1(2H)-quinoxalinyl)-b-D-ribofuranoside
(3e, C20H26N2O5)
Yellow crystals (57 %); m.p.: 117–119 °C; 1H NMR
(250 MHz, CDCl3): d = 1.22 (s, 3H, CH3), 1.37 (s, 3H,
CH3), 2.29 (s, 3H, CH3), 2.37 (s, 3H, CH3), 2.52 (s, 3H,
CH3), 3.41 (s, 3H, OCH3), 4.41–4.50 (m, 2H, H-5, H-50),
4.57–4.62 (m, 1H, H-4), 4.72 (d, 1H, J = 5.9 Hz, H-3),
4.91 (d, 1H, J = 5.9 Hz, H-2), 5.00 (s, 1H, H-1), 7.02 (s,
1H, Ar–H), 7.51 (s,1 H, Ar–H) ppm; 13C NMR (62.5 MHz,
CDCl3): d = 19.8 (2 CH3), 20.5 (CH3), 21.8 (CH3), 26.8
(CH3), 55.2 (OCH3), 44.7 (C-5), 82.6 (C-4), 84.0 (C-3),
85.2 (C-2), 110.2 (C-1), 114.2 (C(CH3)2), 127.1, 129.8,
130.2, 132.1, 133.0, 140.3, 155.1 (Ar–C), 158.2 (CO) ppm;
MS: m/z (%) = 374.0.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(3-methyl-
2-oxo-1(2H)-quinoxalinyl)-b-D-ribofuranoside
(3b, C18H22N2O5)
Yellow crystals (64 %); m.p.: 82–83 °C; 1H NMR
(250 MHz, CDCl3): d = 1.20 (s, 3H, CH3), 1.35 (s, 3H,
CH3), 2.53 (s, 3H, CH3), 3.41 (s, 3H, OCH3), 3.82–3.99 (m,
1H, H-50), 4.41–4.68 (m, 2H, H-4, H-5), 4.75 (d, 1H,
J = 5.9 Hz, H-3), 4.85 (d, 1H, J = 5.9 Hz, H-2), 4.98 (s,
1H, H-1), 7.23–7.48 (m, 2H, Ar–H), 7.52–7.68 (m, 2H, Ar–
H) ppm; 13C NMR (62.5 MHz, CDCl3): d = 21.8 (CH3),
25.1 (CH3), 26.8 (CH3), 45.3 (C-5), 56.6 (OCH3), 82.3 (C-
4), 84.4 (C-3), 85.2 (C-2), 100.2 (C-1), 113.2 (C(CH3)2),
114.3, 124.4, 130.1, 130.3, 132.0, 132.2, 155.0 (Ar–
C),157.2 (CO) ppm.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(6,7-dimethyl-2-
oxo-3-phenyl-1(2H)-quinoxalinyl)-b-D-ribofuranoside
(3f, C25H28N2O5)
Yelow crystals (60 %); m.p.: 137–139 °C; 1H NMR
(250 MHz, CDCl3): d = 1.25 (s, 3H, CH3), 1.46 (s, 3H,
CH3), 2.37 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.45 (s, 3H,
OCH3), 3.90–4.05 (m, 1H, H-5), 4.51–4.70 (m, 2H, H-4,
H-50), 4.78 (d, 1 H, J = 6.0 Hz, H-3), 4.93 (d, 1H,
J = 6.0 Hz, H-2), 5.08 (s, 1H, H-1), 7.18 (s, 1H, Ar–H),
7.40–7.55 (m, 3H, Ar–H), 7.70 (s, 1H, Ar–H), 8.21–8.38
(m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz, CDCl3):
d = 19.0 (CH3), 20.6 (CH3), 24.8 (CH3), 26.3 (CH3), 44.4
(C-5), 55.2 (OCH3), 82.1 (C-4), 83.7 (C-3), 85.3 (C-2),
110.1 (C-1), 122.2 (C(CH3)2), 113.9, 127.9, 129.3, 129.6,
129.9, 130.2, 130.8, 131.8, 132.9, 136.1, 140.5, 152.6 (Ar–
C), 154.6 (CO) ppm.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(2-oxo-3-phenyl-
1(2H)-quinoxalinyl)-b-D-ribofuranoside
(3c, C23H24N2O5)
Yellow crystals (60 %); m.p.: 90–92 °C; 1H NMR
(250 MHz, CDCl3): d = 1.22 (s, 3H, CH3), 1.39 (s, 3H,
CH3), 3.43 (s, 3H, OCH3), 3.93 (m, 1H, H-50), 4.45–4.62
(m, 2H, H-4, H-5), 4.76 (d, 1H, J = 5.9 Hz, H-3), 4.97 (d,
1H, J = 5.9 Hz, H-2), 5.03 (s, 1H, H-1), 7.24–7.57 (m, 5H,
Ar–H), 7.84–7.95 (m, 2H, Ar–H), 8.10–8.28 (m, 2H, Ar–H)
ppm; 13C NMR (62.5 MHz, CDCl3): d = 24.8 (CH3), 26.3
(CH3), 44.7 (C-5), 55.3 (OCH3), 82.2 (C-4), 83.7 (C-3),
85.3 (C-2), 110.0 (C-1), 112.3 (C(CH3)2), 113.5, 123.9,
127.9, 129.4, 130.3, 130.4, 130.8, 132.1, 133.4, 135.8,
153.9 (Ar–C),154.6 (CO) ppm; MS: m/z (%) = 408.0.
Methyl
5-deoxy-2,3-O-isopropylidene-5-(quinoxaline-2-
yloxy)-b-D-ribofuranoside (4a, C17H20N2O5)
White crystals (24 %); m.p.: 61–63 °C; 1H NMR
(250 MHz, CDCl3): d = 1.29 (s, 3H, CH3), 1.46 (s, 3H,
CH3), 3.30 (s, 3H, OCH3), 4.48–4.41 (m, 2H, H-5, H-50),
4.59–4.50 (m, 1H, H-4), 4.62 (d, 1H, J = 6.0 Hz, H-3),
4.80 (d, 1H, J = 6.0 Hz, H-2), 5.00 (s, 1H, H-1), 7.64–7.47
(m, 2H, Ar–H), 7.80–7.76 (m, 1H, Ar–H), 7.98–7.94 (m,
1H, Ar–H), 8.46 (s, 1H, CH) ppm; 13C NMR (62.5 MHz,
CDCl3): d = 24.9 (CH3), 26.4 (CH3), 54.8 (OCH3), 66.4
(C-5), 81.9 (C-4), 84.2 (C-3), 85.2 (C-2), 109.4 (C-1),
112.5 (C(CH3)2), 126.6, 127.1, 128.9, 130.0, 138.9, 139.3,
140.0, 156.6 (Ar–C) ppm; MS: m/z (%) = 332.0.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(6,7-dimethyl-2-
oxo-1(2H)-quinoxalinyl)-b-D-ribofuranoside
(3d, C19H24N2O5)
White crystals (59 %); m.p.: 79–81 °C; 1H NMR
(250 MHz, CDCl3): d = 1.25 (s, 3H, CH3), 1.42 (s, 3H,
CH3), 2.30 (s, 3H, CH3), 2.45 (s, 3H, CH3), 3.41 (s, 3H,
OCH3), 3.84–3.91 (m, 1H, H-5), 4.40–4.52 (m, 1H, H-50),
4.70–4.75 (m, 1H, H-4), 4.84 (d, 1H, J = 6.0 Hz, H-3),
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I. A. I. Ali, S. M. El Rayes
Methyl 5-deoxy-2,3-O-isopropylidene-5-
7.64 (s, 1H, Ar–H) ppm; 13C NMR (62.5 MHz, CDCl3):
d = 19.7 (CH3), 20.0 (CH3), 25.0 (CH3), 26.7 (CH3), 29.8
(CH3), 56.1 (OCH3), 66.2 (C-5), 82.4 (C-4), 84.0 (C-3),
85.1 (C-2), 110.0 (C-1), 113.4 (C(CH3)2), 126.0, 128.0,
136.5, 138.0, 138.2, 138.3, 139.1, 146.5, 156.0 (Ar–C) ppm.
(3-methylquinoxaline-2-yloxy)-b-D-ribofuranoside
(4b, C18H22N2O5)
White crystals (26 %); m.p.: 79–81 °C; 1H NMR (250 MHz,
CDCl3): d = 1.22 (s, 3H, CH3), 1.48 (s, 3H, CH3), 2.55 (s,
3H, CH3), 3.32 (s, 3H, OCH3), 4.24–4.32 (m, 1H, H-5),
4.40–4.53 (m, 2H, H-4, H-50), 4.61 (d, 1H, J = 5.8 Hz, H-3),
4.80 (d, 1H, J = 5.8 Hz, H-2), 4.98 (s, 1H, H-1), 7.15–7.55
(m, 2H, Ar–H), 7.70–7.91 (m, 2H, Ar–H) ppm; 13C NMR
(62.5 MHz, CDCl3): d = 20.2 (CH3), 25.1 (CH3), 26.5
(CH3), 54.7 (OCH3), 66.4 (C-5), 82.3 (C-4), 84.2 (C-3), 85.1
(C-2), 110.1 (C-1), 113.8 (C(CH3)2), 126.4, 128.0, 129.1,
130.3, 139.3, 140.0, 147.3, 158.1 (Ar–C) ppm.
Methyl 5-deoxy-2,3-O-isopropylidene-5-(6,7-dimethyl-3-
phenylquinoxaline-2-yloxy)-b-D-ribofuranoside
(4f, C25H28N2O5)
White crystals (21 %); m.p.: 86–88 °C; 1H NMR
(250 MHz, CDCl3): d = 1.31 (s, 3H, CH3), 1.48 (s, 3H,
CH3), 2.44 (s, 6H, 2 CH3), 3.30 (s, 3H, OCH3), 4.56–4.62
(m, 3H, H-4, H-5, H-50), 4.66 (d, 1H, J = 5.9 Hz, H-3),
4.82 (d, 1H, J = 5.9 Hz, H-2), 5.03 (s, 1H, H-1), 7.23–7.45
(m, 3H, Ar–H), 7.43–7.49 (m, 1 H, Ar–H), 7.51–7.60 (m,
1H, Ar–H), 8.10–8.14 (m, 2H, Ar–H) ppm; 13C NMR
(62.5 MHz, CDCl3): d = 19.9 (CH3), 20.2 (CH3), 24.8
(CH3), 26.4 (CH3), 54.8 (OCH3), 66.6 (C-5), 81.9 (C-4),
84.2 (C-3), 85.2 (C-2), 109.4 (C-1), 112.4 (C(CH3)2),
126.1, 128.0, 128.3, 129.3, 129.6, 136.2, 136.7, 137.9,
138.1, 139.9, 145.1, 154.5 (Ar–C) ppm.
Methyl 5-deoxy-2,3-O-isopropylidene-5-
(3-phenylquinoxaline-2-yloxy)-b-D-ribofuranoside
(4c, C23H24N2O5)
White crystals (19 %); m.p.: 73–74 °C; 1H NMR
(250 MHz, CDCl3): d = 1.32 (s, 3H, CH3), 1.49 (s, 3H,
CH3), 3.30 (s, 3H, OCH3), 4.61–4.68 (m, 2H, H-5, H-50),
4.67–4.72 (m, 2H, H-3, H-4), 4.82 (d, 1H, J = 6.0 Hz,
H-2), 5.04 (s, 1H, H-1), 7.24–7.86 (m, 5H, Ar–H),
8.03–8.09 (m, 1H, Ar–H), 8.12–8.18 (m, 3H, Ar–H) ppm;
13C NMR (62.5 MHz, CDCl3): d = 24.8 (CH3), 26.3
(CH3), 54.7 (OCH3), 66.8 (C-5), 81.7 (C-4), 84.1 (C-3),
85.1 (C-2), 109.4 (C-1), 112.3 (C(CH3)2), 126.5, 126.7,
127.9, 128.3, 128.8, 129.1, 129.5, 129.6, 135.8, 138.9,
139.4, 146.2, 154.6 (Ar–C) ppm; MS: m/z (%) = 408.0.
Deprotection
A solution of 3a–3f or 4a–4f (1.0 mmol) in 25 cm3 60 %
acetic acid was refluxed for 3 h. The solvent was evapo-
rated in vacuo and coevaporated by toluene. The residue
was purified by flash chromatograph (chloroform/methanol
3 to 5 %) to give 5a–5f, 6a–6f, 7a–7f, and 8a–8f.
Methyl 5-deoxy-2,3-O-isopropylidene-5-
(6,7-dimethylquinoxaline-2-yloxy)-b-D-ribofuranoside
(4d, C19H24N2O5)
Method B (deprotection of methyl group); preparation
of 6a–6f and 8a–8f
White crystals (22 %); m.p.: 98–99 °C; 1H NMR
(250 MHz, CDCl3): d = 1.32 (s, 3H, CH3), 1.49 (s, 3H,
CH3), 2.41 (s, 6H, 2 CH3), 3.33 (s, 3H, OCH3), 4.44–4.49
(m, 2H, H-5, H-50), 4.52–4.63 (m, 1H, H-4), 4.66 (d, 1H,
J = 6.0 Hz, H-3), 4.83 (d, 1H, J = 6.0 Hz, H-2), 5.02 (s,
1H, H-1), 7.57 (s, 1H, Ar–H), 7.72 (s, 1H, Ar–H), 8.41 (s,
1H, CH) ppm; 13C NMR (62.5 MHz, CDCl3): d = 19.8
(CH3), 20.1 (CH3), 24.9 (CH3), 26.3 (CH3), 54.8 (OCH3),
66.2 (C-5), 81.9 (C-4), 84.3 (C-3), 85.2 (C-2), 109.1 (C-1),
112.4 (C(CH3)2), 126.6, 128.2, 136.4, 137.7, 138.1, 140.2,
138.5, 156.4 (Ar–C) ppm.
A solution of 5a-5f or 7a-7f (1.0 mmol) in 25 cm3 60 %
acetic acid was refluxed for 2 h. The solvent was evapo-
rated in vacuo and coevaporated by toluene. The residue
was purified by flash chromatograph (chloroform/methanol
5 %) to give 6a–6f and 8a–8f.
Methyl 5-deoxy-5-(2-oxo-1(2H)-quinoxalinyl)-b-
D-ribofuranoside (5a, C14H16N2O5)
White crystals (53 %); m.p.: 122–124 °C; 1H NMR
(250 MHz, DMSO-d6): d = 3.34 (s, 3H, OCH3), 3.52
(brs, 1H, OH), 3.91–3.96 (m, 1H, H-50), 4.20–4.26 (m, 1H,
H-5), 4.30–4.37 (m, 1H, H-4), 4.54–4.69 (m, 2H, H-2,
H-3), 4.76 (s, 1H, H-1), 5.28 (m, 1H, OH), 7.50–7.57 (m,
1H, Ar–H), 7.70–7.76 (m, 2H, Ar–H), 7.81–8.00 (m, 1H,
Ar–H), 8.42 (s, 1H, CH) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 44.6 (C-5), 54.8 (OCH3), 73.0 (C-4), 74.3
(C-3), 78.9 (C-2), 108.6 (C-1), 115.5, 123.4, 128.2, 129.7,
130.7, 132.8, 150.2 (Ar–C), 154.5 (CO) ppm; MS: m/z
(%) = 292.0.
Methyl 5-deoxy-2,3-O-isopropylidene-5-
(3,6,7-trimethylquinoxaline-2-yloxy)-b-D-ribofuranoside
(4e, C20H26N2O5)
White crystals (24 %); m.p.: 95–97 °C; 1H NMR
(250 MHz, CDCl3): d = 1.32 (s, 3H, CH3), 1.48 (s, 3H,
CH3), 2.39 (s, 3H, CH3), 2.60 (s, 6H, 2 CH3), 3.31 (s, 3H,
OCH3), 4.46–4.51 (m, 2H, H-5, H-50), 4.55–4.61 (m, 1H,
H-4), 4.65 (d, 1H, J = 6.0 Hz, H-3), 4.81 (d, 1H,
J = 6.0 Hz, H-2), 5.02 (s, 1H, H-1), 7.53 (s, 1H, Ar–H),
123

Synthesis of quinoxaline reverse ribofuranosides
Methyl 5-deoxy-5-(3-methyl-2-oxo-1(2H)-quinoxalinyl)-b-
D-ribofuranoside (5b, C15H18N2O5)
Methyl
5-deoxy-5-(6,7-dimethyl-2-oxo-3-phenyl-1(2H)-
quinoxalinyl)-b-D-ribofuranoside (5f, C22H24N2O5)
White crystals (60 %); m.p.: 138–139 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.64 (s, 3H, CH3), 3.40 (s,
3H, OCH3), 3.58 (brs, 1H, OH), 4.01 (brs, 1H, OH),
4.21–4.48 (m, 3H, H-4, H-5 H-50), 4.55–4.70 (m, 2H, H-2,
H-3), 4.80 (s, 1H, H-1), 7.48–7.60(m, 2H, Ar–H),
7.70–7.92 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 21.2 (CH3), 44.9 (C-5), 54.8 (OCH3), 73.0
(C-4), 74.3 (C-3), 79.0 (C-2), 108.7 (C-1), 115.1
(C(CH3)2), 123.0, 123.2, 128.8, 129.3, 132.1, 132.7,
154.4 (Ar–C), 157.6 (CO) ppm.
White crystals (60 %); m.p.: 140–142 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.35 (s, 3H, CH3), 2.42 (s,
3H, CH3), 3.26 (s, 3H, OCH3), 3.80–3.87 (m, 1H, H-5),
4.12–4.31 (m, 2H, H-4, H-50), 4.47–4.63 (m, 2H, H-2,
H-3), 4.65 (s, 1H, H-1), 5.04–4.14 (brs, 1H, OH), 5.15–5.19
(brs, 1H, OH), 7.47 (s, 1H, Ar–H), 7.50–7.55 (m, 3H, Ar–
H), 7.68 (s, 1H, Ar–H), 8.26–8.33 (m, 2H, Ar–H) ppm; 13
C
NMR (62.5 MHz, DMSO-d6): d = 18.5 (CH3), 19.9
(CH3), 45.1 (C-5), 54.6 (OCH3), 72.9 (C-4), 74.1 (C-3),
78.9 (C-2), 108.4 (C-1), 115.3, 127.7, 129.1, 129.5, 129.7,
130.8, 132.1, 136.0, 139.8, 151.5 (Ar–C), 153.8 (CO) ppm.
Methyl 5-deoxy-5-(2-oxo-3-phenyl-1(2H)-quinoxalinyl)-b-
D-ribofuranoside (5c, C20H20N2O5)
5-Deoxy-5-(2-oxo-1(2H)-quinoxalinyl)-b-D-ribofuranose
(6a, C13H14N2O5)
White crystals (58 %); m.p.: 125–127 °C; 1H NMR
(250 MHz, DMSO-d6): d = 3.31 (s, 3H, OCH3),
3.82–3.89 (m, 1H, H-5), 4.64–4.70 (m, 2H, H-4, H-50),
4.82–4.92 (m, 2H, H-2, H-3), 5.02 (s, 1H, H-1), 5.09–5.11
(brs, 2H, 2 OH), 7.32–7.63 (m, 5H, Ar–H), 7.78–7.82 (m,
2H, Ar–H), 8.01–8.22 (m, 2H, Ar–H) ppm; 13C NMR
(62.5 MHz, DMSO-d6): d = 44.9 (C-5), 54.2 (OCH3), 81.8
(C-4), 83.2 (C-3), 84.8 (C-2), 109.5 (C-1), 114.3, 124.2,
128.2, 129.0, 130.2, 130.9, 134.1, 135.2, 140.0, 152.4 (Ar–
C), 155.2 (CO) ppm.
White crystals (30 %, method B 75 %); m.p.: 158–160 °C;
1H NMR (250 MHz, DMSO-d6): d = 3.90 (brs, 1H, OH),
4.05–4.20 (m, 2H, H-5, H-50), 4.27 (brs, 2H, 2 OH),
4.34–4.39 (m, 2H, H-4), 4.52 (d, 1H, J = 4.5 Hz, H-3),
4.58 (d, 1H, J = 4.5 Hz, H-2), 4.92 (s, 1H, H-1), 7.30–7.37
(m, 1H, Ar–H), 7.65–7.59 (m, 2H, Ar–H), 7.71–7.79 (m,
1H, Ar–H), 8.21 (s, 1H, CH) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 45.6 (C-5), 72.9 (C-4), 75.5 (C-3), 78.5
(C-2), 102.0 (C-1), 115.8, 123.3, 129.6, 130.8, 132.8,
132.9, 150.0 (Ar–C), 154.5 (CO) ppm.
Methyl 5-deoxy-5-(6,7-dimethyl-2-oxo-1(2H)-
quinoxalinyl)-b-D-ribofuranoside (5d, C16H20N2O5)
5-Deoxy-5-(3-methyl-2-oxo-1(2H)-quinoxalinyl)-b-D-
ribofuranose (6b, C14H16N2O5)
White crystals (55 %); m.p.: 143–145 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.28 (s, 3H, CH3), 2.35 (s,
3H, CH3), 3.39 (s, 3H, OCH3), 3.72–3.85 (m, 1H, H-5),
4.02–4.20 (m, 2H, H-4, H-50), 4.40–4.48 (m, 2H, H-2,
H-3), 4.58 (s, 1H, H-1), 4.93–5.08 (brs, 1H, OH), 5.10–5.15
(brs, 1H, OH), 7.40 (s, 1H, Ar–H), 7.56 (s, 1H, Ar–H), 8.13
(s, 1H, CH) ppm; 13C NMR (62.5 MHz, DMSO-d6):
d = 19.9 (CH3), 20.0 (CH3), 44.5 (C-5), 54.5 (OCH3), 72.9
(C-4), 74.1 (C-3), 78.8 (C-2), 108.4 (C-1), 115.5, 129.4,
130.6, 131.2, 131.9, 140.2, 148.6 (Ar–C), 154.3 (CO) ppm.
Brown crystals (28 %, method B 65 %); m.p.: 169–170 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.40 (s, 3H, CH3),
3.48 (brs, 3H, 3 OH), 4.28–4.19 (m, 1H, H-5), 4.43–4.29
(m, 2H, H-4, H-50), 4.50 (d, 1H, J = 4.8 Hz, H-3), 4.56 (d,
1H, J = 4.8 Hz, H-2), 4.87 (s, 1H, H-1), 7.53–7.24 (m, 2H,
Ar–H), 7.87–7.62 (m, 2H, Ar–H) ppm; 13C NMR
(62.5 MHz, DMSO-d6): d = 21.1 (CH3), 45.9 (C-5), 72.9
(C-4), 75.4 (C-3), 78.5 (C-2), 101.9 (C-1), 115.3, 123.1,
128.6, 129.3, 132.1, 132.9, 154.4 (Ar–C), 157.5 (CO) ppm.
Methyl 5-deoxy-5-(3,6,7-trimethyl-2-oxo-1(2H)-
5-Deoxy-5-(2-oxo-3-phenyl-1(2H)-quinoxalinyl)-b-D-
ribofuranose (6c, C19H18N2O5)
quinoxalinyl)-b-D-ribofuranoside (5e, C17H22N2O5)
White crystals (58 %); m.p.: 177–179 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.29 (s, 3H, CH3), 2.35 (s,
3H, CH3), 2.41 (s, 3H, CH3), 3.21 (s, 3H, OCH3),
4.04–4.19 (m, 2H, H-5, H-50), 4.23–4.35 (m, 1H, H-4),
4.37–4.42 (m, 1H, H-3), 4.58 (d, 1H, J = 4.7 Hz, H-2),
4.67 (s, 1H, H-1), 5.01 (brs, 1H, OH), 5.08 (brs, 1H, OH),
7.37 (s, 1H, Ar–H), 7.50 (s,1 H, Ar–H) ppm; 13C NMR
(62.5 MHz, DMSO-d6): d = 18.5 (CH3), 19.9 (CH3), 21.0
(CH3), 44.9 (C-5), 54.6 (OCH3), 72.9 (C-4), 74.1 (C-3),
78.9 (C-2), 108.4 (C-1), 115.4, 128.2, 130.4, 130.6, 131.6,
138.4, 154.4 (Ar–C), 156.1 (CO) ppm.
White crystals (26 %, method B 79 %); m.p.: 151–153 °C;
1H NMR (250 MHz, DMSO-d6): d = 3.33 (brs, 2H, 2
OH), 3.74–3.91 (m, 1H, H-5), 4.09–4.32 (m, 2H, H-4,
H-50), 4.49–4.61 (m, 2H, H-2, H-3), 4.68 (s, 1H, H-1),
5.03–5.08 (brs, 1H, OH), 5.09 (d, 1H, J = 4.3 Hz, 1H,
OH), 7.34–7.65 (m, 5H, Ar–H), 7.67–7.93 (m, 2H, Ar–H),
8.13–8.19 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 44.9 (C-5), 74.4 (C-4), 79.1 (C-3), 80.1
(C-2), 107.1 (C-1), 115.3, 123.5, 126.8, 127.8, 129.3,
129.7, 130.1, 132.4, 133.0, 135.9, 153.0 (Ar–C), 154.0
(CO) ppm.
123

I. A. I. Ali, S. M. El Rayes
5-Deoxy-5-(6,7-dimethyl-2-oxo-1(2H)-quinoxalinyl)-b-D-
ribofuranose (6d, C15H18N2O5)
Methyl 5-deoxy-5-(3-methylquinoxaline-2-yloxy)-b-D-
ribofuranoside (7b, C15H18N2O5):
Brown crystals (21 %, method B 64 %); m.p.: 185–187 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.26 (s, 3H, CH3),
2.33 (s, 3H, CH3), 3.90 (brs, 3H, 3 OH), 4.10–4.32 (m, 3H,
H-4, H-5, H-50), 4.45–4.64 (m, 2H, H-3), 4.91–5.02 (m,
2H, H-1, H-2), 7.46 (s, 1H, Ar–H), 7.51 (s, 1H, Ar–H), 8.08
(s, 1H, CH) ppm; 13C NMR (62.5 MHz, DMSO-d6):
d = 18.3 (CH3), 19.9 (CH3), 45.2 (C-5), 72.9 (C-4), 75.5
(C-3), 78.3 (C-2), 101.9 (C-1), 129.3, 130.8, 131.3, 132.0,
132.1, 140.3, 148.5 (Ar–C), 154.5 (CO) ppm.
White crystals (58 %); m.p.: 115–117 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.50 (s, 3H, CH3), 3.28 (s, 3H,
OCH3), 3.67–3.83 (m, 2H, H-5, H-50), 4.07–4.13 (m, 1H,
H-4), 4.35–4.41 (m, 2H, H-2, H-3), 4.61 (s, 1H, H-1), 4.99
(brs, 1H, OH), 5.11 (m, 1H, OH), 7.48–7.59 (m, 2H, Ar–H),
7.61–7.85 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 19.8 (CH3), 54.2 (OCH3), 66.5 (C-5), 74.1
(C-4), 79.3 (C-3), 79.9 (C-2), 108.1 (C-1), 126.4, 127.7,
129.0, 130.1, 137.9, 138.9, 147.9, 155.7 (Ar–C) ppm.
5-Deoxy-5-(3,6,7-trimethyl-2-oxo-1(2H)-quinoxalinyl)-b-
D-ribofuranose (6e, C16H20N2O5)
Methyl 5-deoxy-5-(3-phenylquinoxaline-2-yloxy)-b-D-
ribofuranoside (7c, C20H20N2O5)
White crystals (28 %, method B 54 %); m.p.: 173–175 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.36 (s, 3H, CH3),
2.42 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.82 (brs, 2H, 2 OH),
4.00 (brs, 1H, OH), 4.15–4.40 (m, 2H, H-5, H-50),
4.57–4.68 (m, 2H, H-3, H-4), 4.92–5.12 (m, 2H, H-1,
H-2), 7.51 (s, 1H, Ar–H), 7.55 (s, 1H, Ar–H) ppm; 13C
NMR (62.5 MHz, DMSO-d6): d = 18.6 (CH3), 19.9
(CH3), 21.0 (CH3), 45.5 (C-5), 72.8 (C-4), 75.5 (C-3),
78.3 (C-2), 101.8 (C-1), 128.5, 130.4, 130.6, 130.7, 131.5,
138.5, 154.3 (Ar–C), 156.0 (CO) ppm.
White crystals (54 %); m.p.: 88–90 °C; 1H NMR
(250 MHz, DMSO-d6): d = 3.35 (s, 3H, OCH3),
4.61–4.71 (m, 3H, H-4, H-5, H-50), 4.76–4.87 (m, 2H,
H-2, H-3), 5.00 (s, 1H, H-1), 5.12–5.32 (brs, 2H, 2 OH),
7.49–7.82 (m, 5H, Ar–H), 7.92–8.00 (m, 1H, Ar–H),
8.14–8.25 (m, 3H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 53.9 (OCH3), 65.4 (C-5), 82.0 (C-4), 84.3
(C-3), 85.3 (C-2), 110.0 (C-1), 126.0, 126.5, 128.3, 128.7,
129.1, 129.4, 130.0, 132.0, 134.8, 138.4, 139.2, 145.2,
155.0 (Ar–C) ppm.
5-Deoxy-5-(6,7-dimethyl-2-oxo-3-phenyl-1(2H)-
Methyl 5-deoxy-5-(6,7-dimethylquinoxaline-2-yloxy)-b-D-
ribofuranoside (7d, C16H20N2O5
quinoxalinyl)-b-D-ribofuranose (6f, C21H22N2O5)
White crystals (30 %, method B 56 %); m.p.: 180–182 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.34 (s, 3H, CH3),
2.41 (s, 3H, CH3), 2.51 (brs, 1H, OH), 3.50 (brs, 1H, OH),
3.79–3.90 (m, 1H, H-5), 4.00 (brs, 1H, OH), 4.28–4.33 (m,
1H, H-50), 4.50–4.82 (m, 2H, H-3, H-4), 4.90–5.08 (m, 2H,
H-1, H-2), 7.40–7.53 (s, 4H, Ar–H), 7.64 (s, 1H, Ar–H),
8.21–8.30 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 18.5 (CH3), 20.0 (CH3), 45.8 (C-5), 72.9
(C-4), 75.5 (C-3), 78.4 (C-2), 101.9 (C-1), 115.6, 127.6,
129.1, 129.3, 129.7, 130.8, 130.9, 131.9, 132.1, 136.0,
139.9, 151.3 (Ar–C), 153.8 (CO) ppm.
White crystals (55 %); m.p.: 111–113 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.52 (s, 6H, 2 CH3), 3.32 (s,
3H, OCH3), 3.97 (brs, 1H, OH), 4.21–4.38 (m, 2H, H-5,
H-50), 4.46–4.54 (m, 2H, H-3, H-4), 4.77–4.83 (m, 1H,
H-2), 4.85 (s, 1H, H-1), 5.35 (brs, 1H, OH), 7.69 (s, 1H,
Ar–H), 7.85 (s, 1H, Ar–H), 8.59 (s, 1H, CH) ppm; 13C
NMR (62.5 MHz, DMSO-d6): d = 19.3 (CH3), 19.7
(CH3), 54.2 (OCH3), 67.3 (C-5), 71.3 (C-4), 74.1 (C-3),
80.1 (C-2), 108.3 (C-1), 126.2, 127.8, 136.3, 137.2, 137.9,
138.2, 140.3, 156.6 (Ar–C) ppm.
Methyl 5-deoxy-5-(3,6,7-trimethylquinoxaline-2-yloxy)-b-
D-ribofuranoside (7e, C17H22N2O5)
Methyl 5-deoxy-5-(quinoxaline-2-yloxy)-b-D-
ribofuranoside (7a, C14H16N2O5)
White crystals (62 %); m.p.: 144–146 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.30 (s, 6H, 2 CH3), 2.33 (s,
3H, CH3), 3.09 (s, 3H, OCH3), 3.78–3.88 (m, 1H, H-5),
4.00–4.12 (m, 2H, H-4, H-50), 4.33–4.61 (m, 2H, H-2,
H-3), 4.63 (s, 1H, H-1), 5.35 (m,1 H, OH), 4.92–4.99 (brs,
1H, OH), 5.02–5.14 (brs, 1H, OH), 7.51 (s, 1H, Ar–H),
7.61 (s, 1H, Ar–H) ppm; 13C NMR (62.5 MHz, DMSO-d6):
d = 19.4 (CH3), 19.6 (CH3), 19.7 (CH3), 54.2 (OCH3),
66.3 (C-5), 70.8 (C-4), 74.2 (C-3), 80.0 (C-2), 108.2 (C-1),
125.9, 127.1, 135.9, 136.8, 137.5, 138.8, 146.5, 155.5 (Ar–
C) ppm; MS: m/z (%) = 334.0.
White crystals (61 %); m.p.: 102–104 °C; 1H NMR
(250 MHz, DMSO-d6): d = 3.17 (s, 3H, OCH3),
3.80–3.92 (m, 1H, H-5), 4.08–4.21 (m, 2H, H-4, H-50),
4.37–4.50 (m, 1H, H-3), 4.65–4.78 (m, 2H, H-2), 4.80 (s,
1H, H-1), 5.11–5.21 (m, 2H, 2 OH), 7.30–7.59 (m, 1H, Ar–
H), 7.62–7.79 (m, 2H, Ar–H), 7.83–8.00 (m, 1H, Ar–H),
8.58 (s, 1H, CH) ppm; 13C NMR (62.5 MHz, DMSO-d6):
d = 54.2 (OCH3), 67.5 (C-5), 71.3 (C-4), 74.0 (C-3), 80.0
(C-2), 108.3 (C-1), 126.8, 128.6, 130.0, 130.4, 138.4,
139.5, 139.7, 156.9 (Ar–C) ppm; MS: m/z (%) = 292.0.
123

Synthesis of quinoxaline reverse ribofuranosides
Methyl
5-deoxy-5-(6,7-dimethyl-3-phenylquinoxaline-2-
1H, H-5), 4.48–4.63 (m, 2H, H-4, H-50), 4.70–4.86 (m, 2H,
H-2, H-3), 5.18 (s, 1H, H-1), 7.72 (s, 1H, Ar–H), 7.87 (s,
1H, Ar–H), 8.60 (s, 1H, CH) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 19.3 (CH3), 19.7 (CH3), 68.4 (C-5), 71.4
(C-4), 75.3 (C-3), 79.2 (C-2), 102.0 (C-1), 126.2, 127.8,
136.3, 137.1, 138.0, 138.3, 140.4, 156.7 (Ar–C) ppm.
yloxy)-b-D-ribofuranoside (7f, C22H24N2O5)
Brown crystals (57 %); m.p.: 156–158 °C; 1H NMR
(250 MHz, DMSO-d6): d = 2.32 (s, 3H, CH3), 2.36 (s,
3H, CH3), 3.28 (s, 3H, OCH3), 3.85 (brs, 1H, OH),
4.32–4.45 (m, 3H, H-4, H-5, H-50), 4.50–4.64 (m, 2H, H-2,
H-3), 4.85 (s, 1H, H-1), 5.12–5.21 (brs, 1H, OH), 7.10–7.56
(m, 4H, Ar–H), 7.60–7.75 (m, 1H, Ar–H), 8.20–8.38 (m,
2H, Ar–H) ppm; 13C NMR (62.5 MHz, DMSO-d6):
d = 19.4 (CH3), 19.8 (CH3), 54.2 (OCH3), 67.3 (C-5),
74.2 (C-4), 77.2 (C-3), 79.8 (C-2), 108.3 (C-1), 127.7,
128.0, 128.5, 129.5, 129.8, 130.1, 130.6, 132.0, 135.9,
136.7, 137.2, 140.0, 140.2, 154.6 (Ar–C) ppm.
5-Deoxy-5-(3,6,7-trimethylquinoxaline-2-yloxy)-b-D-
ribofuranose (8e, C16H20N2O5)
Brown crystals (24 %, method B 53 %); m.p.: 191–193 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.35 (s, 6H, 2 CH3),
2.51 (s, 3 H,CH3), 4.21 (brs, 3H, 3 OH), 4.31–4.38 (m, 2H,
H-5, H-50), 4.47–4.69 (m, 3H, H-2, H-3, H-4), 5.01 (s, 1H,
H-1), 7.52 (s, 1H, Ar–H), 7.61 (s, 1H, Ar–H) ppm; 13C
NMR (62.5 MHz, DMSO-d6): d = 19.4 (CH3), 19.6
(CH3), 19.8 (CH3), 67.8 (C-5), 71.2 (C-4), 75.3 (C-3),
79.2 (C-2), 101.8 (C-1), 125.9, 127.1, 135.8, 136.7, 137.5,
138.7, 146.4, 155.5 (Ar–C) ppm; MS: m/z (%) = 320.0.
5-Deoxy-5-(quinoxaline-2-yloxy)-b-D-ribofuranose
(8a, C13H14N2O5)
White crystals (26 %, method B 61 %); m.p.: 167–169 °C;
1H NMR (250 MHz, DMSO-d6): d = 4.20–4.45 (m, 3H, 3
OH), 4.51–4.58 (m, 1H, H-5), 4.62–4.68 (m, 2H, H-4,
H-50), 4.71–4.86 (m, 2H, H-2, H-3), 5.09 (s, 1H, H-1),
7.50–7.57 (m, 1H, Ar–H), 7.61–7.69 (m, 2H, Ar–H),
7.72–7.91 (m, 1H, Ar–H), 8.47 (s, 1H, CH) ppm; 13C NMR
(62.5 MHz, DMSO-d6): d = 68.3 (C-5), 71.3 (C-4), 75.2
(C-3), 79.1 (C-2), 101.8 (C-1), 122.4, 126.6, 128.0, 128.4,
130.2, 138.1, 139.3, 156.7 (Ar–C) ppm.
5-Deoxy-5-(6,7-dimethyl-3-phenylquinoxaline-2-yloxy)-b-
D-ribofuranose (8f, C21H22N2O5)
Yellow crystals (28 %, method
B
57 %); m.p.:
131–133 °C; 1H NMR (250 MHz, DMSO-d6): d = 2.44
(s, 3H, CH3), 2.47 (s, 3H, CH3), 4.23 (brs, 1H, OH),
4.55–4.72 (m, 2H, H-5, H-50), 4.81–5.03 (m, 2H, H-3,
H-4), 5.06–5.13 (m, 2H, H-1, H-2), 6.03 (d, 1H,
J = 8.0 Hz, 1H, OH), 6.50 (d, 1H, J = 4.7 Hz, 1H, OH),
7.56–7.69 (m, 4H, Ar–H), 7.80–7.87 (m, 1H, Ar–H),
8.12–8.26 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 19.5 (CH3), 19.8 (CH3), 66.7 (C-5), 75.3
(C-4), 79.1 (C-3), 79.5 (C-2), 101.9 (C-1), 125.7, 128.1,
129.5, 135.7, 136.7, 137.1, 137.6, 140.2, 144.2, 144.4,
154.6 (Ar–C) ppm.
5-Deoxy-5-(3-methylquinoxaline-2-yloxy)-b-D-
ribofuranose (8b, C14H16N2O5)
White crystals (22 %, method B 54 %); m.p.: 126–128 °C;
1H NMR (250 MHz, DMSO-d6): d = 2.71 (s, 3H, CH3),
4.00–4.36 (m, 4H, H-4, H-5, H-50, OH), 4.47–4.68 (m, 4H,
H-2, H-3, 2 OH), 4.87 (s, 1H, H-1), 7.68–7.80 (m, 2H, Ar–
H), 7.82–8.08 (m, 2H, Ar–H) ppm; 13C NMR (62.5 MHz,
DMSO-d6): d = 19.7 (CH3), 66.4 (C-5), 70.8 (C-4), 74.1
(C-3), 79.6 (C-2), 108.3 (C-1), 125.4, 126.4, 127.6, 128.9,
137.6, 139.0, 147.3, 155.5 (Ar–C) ppm; MS: m/z
(%) = 292.0.
References
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Brown crystals (27 %, method B 61 %); m.p.: 116–118 °C;
1H NMR (250 MHz, DMSO-d6): d = 3.50 (brs, 2H, 2
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