Synthesis and biological evaluation of S-glycosylated pyridines

Article abstract of DOI:10.1081/NCN-120003286

The formation of thioglycosides 7a-j and 10a-j via the reaction of sodium salts of thiopyridines 3a-e with glycosyl bromides 6a,b has been studied. Comparison with the products obtained from silylated thiopyridines 8a-e and peracetylated sugars 9a,b is made. ¹³C NMR was utilized to elucidate the proposed structures of the products.

Full text of DOI:10.1081/NCN-120003286

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 S-
GLYCOSYLATED PYRIDINES
Adel M. E. Attia
To cite this article: Adel M. E. Attia (2002) SYNTHESIS AND BIOLOGICAL EVALUATION OF S-
GLYCOSYLATED PYRIDINES, Nucleosides, Nucleotides and Nucleic Acids, 21:3, 207-216, DOI:
10.1081/NCN-120003286
To link to this article: http://dx.doi.org/10.1081/NCN-120003286
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS, 21(3), 207–216 (2002)
SYNTHESIS AND BIOLOGICAL EVALUATION
OF S-GLYCOSYLATED PYRIDINES
Adel M. E. Attia
Department of Chemistry, Faculty of Education, University of
Tanta (Kafr El-Sheikh Branch), Egypt
ABSTRACT
The formation of thioglycosides 7a-j and 10a-j via the reaction of so-
dium salts of thiopyridines 3a-e with glycosyl bromides 6a,b has been
studied. Comparison with the products obtained from silylated thiopyr-
idines 8a-e and peracetylated sugars 9a,b is made. 13C NMR was utilized
to elucidate the proposed structures of the products.
INTRODUCTION
Various nucleoside analogues are well-known as important agents in the
field of chemotherapy of cancer and viral diseases. Among them, 1-b-D-arabi-
nosylcytosine1forthetreatmentofacutemyeloblasticleukemiaand30-deoxy-30-
azidothymidine2, dideoxycytidine3 and dideoxy inosine4 for the treatment of
acquired immunodeficiency syndrome (AIDS). A new class of anti-HIV agents
including1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine(HEPT)and1-
(benzoyloxymethyl)-5-ethyl-6-(phenylthio)uracil (BEPU), has been ident-
ified5–7. Such compounds show a high selectivity for the HIV-1 reverse
transcriptase. Other active nucleosides related to HEPT and BEPU, like pyr-
idine and pyrimidine glycosides were recently reported, and some of these
compoundslookpromisingasanti-HIVagents8–11. Asanextensionofourwork
on thiopyridine glycosides, we report herein a synthesis of a new class of
unnatural nucleosides, 2-(b-D-glycopyranosylthio)pyridines. In addition, we
have tested these glycosides against HIV.
207
Copyright # 2002 by Marcel Dekker, Inc.
www.dekker.com

208
ATTIA
CHEMISTRY
5-Arylazo-3-cyanopyridine-2(1H)-thiones (4)were prepared in high
yields in two steps from the reaction of cyanothioacetamide (1)with 2-aryl-
hydrazono-1,3-diphenylpropane-1,3-dione (2)according to reported proce-
dures12. The sodium salts 3 could be isolated from the reaction whose
acidification gave 4. A model study on the alkylation of 3 and=or 4 was
carried out using iodomethane by the reaction of one mole of alkylating agent
directly with the sodium salts of 5-arylazo-3-cyanopyridine-2(1H)-thiones 3
or the reaction with 4 in the presence of sodium hydroxide in dry DMF
whereby the same products 5 were obtained in each case (Chart 1). The
structures of compounds 5 were confirmed by their elemental analyses and
spectral data. The 1H NMR spectrum of 5a showed a band at d 2.62 assigned
to S-CH3 group, and its 13C NMR showed signals at d 24 (S-CH3)and 163 (C-
2). These data as well as the mode of the reaction indicated that the site of
alkylation was the sulphur rather than the nitrogen. Compounds 4 bearing a
latent functional substituent were found useful for the synthesis of interesting
S-glycoside derivatives. Thus, it has been found that compounds 3 react with
2, 3, 4, 6-tetra-O-acetyl-a-D-glucopyranosyl bromide or its a-D-galactopyr-
anosyl isomer 6 in acetone to give S-glycosylated pyridines 7a-j (Chart 1).
Compound 7 could also be obtained in good yields by the reaction of 4 with
glycosyl bromides 6 in the presence of aqueous potassium hydroxide. The
structures of the reaction products 7a-j were established and confirmed by
their elemental analyses and spectral data (MS, IR, 1H NMR, 13C NMR). The
analytical data for 7e revealed a molecular ion corresponding to (Mþ 752).
The 1H NMR spectrum showed a doublet at d 6.20 (J ¼ 10.63 Hz)assigned to
the anomeric proton of the glucose moiety with a diaxial orientation of H-10
and H-20 indicating the b-configuration and 4C1 conformation.
The other protons of the glucopyranose ring resonate at d 4.02-5.68,
while the four acetoxy groups appear as four singlets in the 1.76-2.05 region
4
providing further verification of the C1 (D)conformation with b-configura-
tion, since these signals lie within the range expected for equatorial secondary
acetoxy groups. Although the coupling of 3 with 6 could also give the corre-
sponding N-glycosides 11, the formation of 7e was proven using 13C NMR
which revealed the absence of the thione carbon at d 178 and appearance of C-
2 carbon at d 162.8 of the same value of the corresponding S-methyl derivative
5e. Ammonolysis of mononucleosides 7a-j furnished the corresponding 2-(b-
D-glycopyranosylthio)pyridines 10a-j in yields of 84–87%. TLC of the free
thioglycosides 10 showed that single compounds were produced, and their
structures were further confirmed by elemental analyses and spectral data. The
analytical data for 10f reveal the molecular ion corresponding to (Mþ 554).
The 1H NMR spectrum of 10f showed the anomeric proton as a doublet at d
5.64 (J ¼ 10.27 Hz), indicating the presence of only the b-D-galactopyranose,
while the signals of the four hydroxy groups of the galactose moiety resonated

S-GLYCOSYLATED PYRIDINES
209
Chart 1.
at d 4.62-5.40 (exchangeable by D2O). The 13C NMR spectrum of 10f was
characterized by a signal at d 84.3 corresponding to the C-10 atom of b-D-
galactopyranose. Another five signals at d 60.8, 63.7, 68.6, 74.8 and 80.1 were
assigned to C-60, C-40, C-20, C-30 and C-50 respectively, while the C-2 of
aglycone appear at d 161.9. With this pyridine thioglycosides as model, it was

210
ATTIA
decided to synthesize these compounds with the silylation method and com-
paring the products for stereochemical consideration. Thus, in a simple
experimental procedure, silylation of thiopyridines 4 followed by a Lewis acid-
catalyzed reaction of the resultant silylthiopyridines 8 with pentaacetyl-b-D-
glycopyranose 9 afforded the S-glycosyl compounds 7, which were shown to
be the same as those obtained from the reaction of 3 with 6 by their melting
points and spectral data. A suggested mechanism for the formation of the S-
glycosides 7 by the silylation method is illustrated in chart 2. In summary, the
glycosides obtained by these syntheses seem promising as potential substrates
for the preparation of other carbohydrate derivatives as deoxy, amino and
azido nucleosides.
Cytotoxicity of thioglycosides 7 and 10 against different types of tumor
viruses and Human Immunodeficiency virus HIV-1 in MT-4 cells in vitro was
examined13. None of these nucleosides showed any significant cytotoxicity up
to 100 mg=mL. None of these nucleosides showed substantial anti-HIV
activity.
EXPERIMENTAL
Melting points are uncorrected. TLC was carried out on aluminum
sheet silica gel 60 F254 (Merck)detected by short UV light. IR Spectra were
obtained (KBr)using a Pye Unicam spectra 1000. 1H NMR and 13C NMR
spectra were measured on a Varian 400 MHz spectrometer in DMSO-d6
using SiMe4 as internal standard. Mass spectra were recorded by EI on a
Varian Mat 311A spectrometer and FAB on a Kratos MS 50 spectrometer.
Analytical data were obtained from the Microanalytical Center at Qatar
University.
Sodium salts of 5-arylazo-3-cyanopyridine-2(1H)-thiones (3). A mixture
of cyanothioacetamide (1)(0.01 mol)and 2-arylhydrazono-1, 3-diphenyl-
propane-1,3-dione (2)(0.01 mol)was dissolved in ethanol (30 mL)
containing sodium ethoxide (0.68 g, 0.01 mol). The mixture was refluxed
for 6 h, and then allowed to stand overnight. The resultant precipitate was
isolated by filtration and crystallized from the appropriate solvent to give
the solid products 3.
5-Arylazo-3-cyanopyridine-2(1H)-thiones (4). The sodium salt 3 was
dissolved in water at 80ꢀC, filtered and neutralized with cold dilute
hydrochloric acid. The resulting solid product was collected by filtration
and washed with distilled water to remove sodium chloride. The product
was dried prior to crystallization from EtOH-DMF to afford the products 412.

S-GLYCOSYLATED PYRIDINES
211
Chart 2.
5-Arylazo-3-cyano-2-methylthiopyridines (5).
MethodA: The sodium salt 3 (0.01 mol)was suspended in ethanol (30 mL).
An excess of methyl iodide (0.015 mol)was then added dropwise to the resulting
suspension. The precipitate obtained after 4 h of stirring at room temperature
was filtered off and crystallized from ethanol to afford the products 5.

212
ATTIA
Method B: A mixture of 4 (0.01 mol), NaOH (0.4 g, 0.01 mol) and
methyl iodide (0.015 mol)in dry DMF (30 mL)was stirred at room tem-
perature for 12 h and then diluted with cold water (100 mL). The resulting
solid product was collected by filtration and crystallized from ethanol to give
the products 5.
1
5a: Yield 53%, mp 138ꢀC; IR 2212(CN)cm ꢁ 1; H NMR d 2.62(s,
SCH3), 7.40-7.98(m, Ar-H); 13C NMR d 24.0(SCH3), 106.8-158.2(Ar-C),
163.0(C-2); MS (ionization method): m=z 406(Mþ); Anal. Calcd for
C25H18N4S: C, 73.89; H, 4.43; N, 13.79. Found: C, 74.11; H, 4.60; N, 13.98.
5b:Yield 51%, mp 131ꢀC; IR 2210(CN)cm ꢁ 1; MS (ionization method):
m=z 485 (Mþ); Anal. Calcd for C25H17N4SBr: C, 61.85; H, 3.50; N, 11.55.
Found: C, 62.14; H, 3.12; N, 11.70.
5c: Yield 50%, mp 122ꢀC; IR 2214(CN)cm ꢁ 1; MS (ionization
method): m=z 440 (Mþ); Anal. Calcd for C25H17N4SCl: C, 68.10; H, 3.86; N,
12.71. Found: C, 68.27; H, 4.04; N, 12.96.
5d: Yield 52%, mp 142ꢀC; IR 2218(CN)cm ꢁ 1 MS (ionization method):
m=z 420 (Mþ); Anal. Calcd for C26H20N4S: C, 74.28; H, 4.76; N, 13.33.
Found: C, 74.52; H, 4.89; N, 13.48.
1
5e: Yield 54%, mp 129ꢀC; IR 2215(CN)cm ꢁ 1; H NMR d 2.58(s,
SCH3), 3.88(s, OCH3), 7.62-8.00(m, Ar-H);13C NMR d 23.8(SCH3), 55.6
(OCH3), 107.0–157.5(Ar-C), 162.9(C-2); MS (ionization method): m=z 436
(Mþ); Anal. Calcd for C26H20N4SO: C, 71.56; H, 4.59; N, 12.84. Found: C,
71.68; H, 4.71; N, 12.95.
3-Cyano-2-(2,3,4,6-Tetra-O-acetyl-b-D-glycopyranosylthio)-pyridines (7).
General coupling procedures: Method A: To a solution of pyridinethione
sodium salts 3a-e (0.01 mol)in acetone (10 mL), a solution of 2,3,4,6-tetra- O-
acetyl-a-D-glycopyranosyl bromide 6 (0.011 mol)in acetone (20 mL)was
added. The reaction mixture was stirred at room temperature until judged to
be complete by TLC (1 to 2 h), using chloroform:ether 4:1, v=v (Rf 0.70–0.74
region). The mixture was evaporated under reduced pressure at 40ꢀC and
the crude glycoside was washed with distilled water to remove the formed
sodium bromide. The product was dried prior to crystallization from ethanol
to afford the products 7a-j.
Method B: To a solution of 2(1H)-pyridinethiones 4 (0.01 mol)in
aqueous potassium hydroxide (0.56 g, 0.01 mol, in 6 mL of distilled water)
was added a solution of 2, 3, 4, 6-tetra-O-acetyl-a-D-glycopyranosyl bromide
6 (0.011 mol)in acetone (30 mL.) The reaction mixture was stirred at room
temperature until judged to be complete by TLC (1 to 2 h)then processed as
described above.
Method C: 3-Cyano-2(1H)-pyridinethiones 4 (0.01 mol)were heated
under reflux, with stirring, under anhydrous conditions for 48 hours with

S-GLYCOSYLATED PYRIDINES
213
hexamethyldisilazane (25 mL)and (NH 4)2SO4 (0.02 g). The excess of HMDS
was removed under diminished pressure, providing the silylated bases 8 as
colourless oils. To a solution of silylated base in dry MeCN (30 mL)was
added a solution of b-D-glucose- or b-D-galactose-pentaacetate (0.011 mol)in
dry MeCN (10 mL), followed by SnCl4 (1.6 mL). The reaction mixture was
stirred at room temperature until reaction was judged complete by TLC, then
poured into saturated NAHCO3 solution and extracted with CHCl3. The
organic layers were dried over MgSO4, filtered and concentrated to give the
crude nucleosides which were purified by recrystallization from ethanol to
afford the products 7a-j.
7a: Yield 73%, mp 116ꢀC; IR 2210(CN), 1750 (CO) cmꢁ 1; 1H NMR d
1.91-2.16(4s, 4CH3CO), 4.09(m, 2H-60), 4.63(m, H-50), 5.03(t, H-40), 5.26(t,
H-30), 5.68(t, H-20), 6.22(d, J ¼ 10.26 Hz, H-10), 7.20-8.01(m, Ar-H); MS
(ionization method): m=z 722(Mþ); Anal. Calcd for C38H34N4SO9: C, 63.16;
H, 4.71; N, 7.76. Found: C, 63.33; H, 4.89; N, 7.92.
1
7b: Yield 67%, mp 127ꢀC; IR 2210(CN), 1750(CO) cmꢁ 1; H NMR d
1.75-2.03(4s, 4CH3CO), 4.09(m, 2H-60 and H-50), 5.06(t, H-40), 5.26(t, H-30),
5.68(t, H-20), 6.21(d, J ¼ 9.73 Hz, H-10), 7.32-7.74(m, Ar-H); MS (ionization
method): m=z 801 (Mþ); Anal. Calcd for C38H33N4BrSO9: C, 56.93; H, 4.12;
N, 6.99. Found: C, 57.17; H, 4.28; N, 7.21.
7c: Yield 69%, mp 143ꢀC; IR (2223), 1754(CO) cmꢁ 1; MS (ionization
method): m=z 756 (Mþ); Anal. Calcd for C38H33N4ClSO9: C, 60.28; H, 4.36;
N, 7.40. Found: C, 60.44; H, 4.51; N, 7.63.
1
7d: Yield 72%, mp 130ꢀC; IR 2222(CN), 1753(CO) cmꢁ 1; H NMR d
1.76-2.08(4s, 4CH3CO), 2.31(s, CH3), 4.12(m, 2H-60 and H-50), 5.01(t, H-40),
5.25(t, H-30), 5.66(t, H-20), 6.18(d, J ¼ 10.62 Hz, H-10), 7.24-7.87(m, Ar-H);
13C NMR d 20.2-20.6(4CH3CO), 21.2(CH3), 62.0(C-60), 68.8(C-40), 71.4(C-
20), 72.9(C-30), 75.0(C-50), 80.3(C-10), 107.1(C-3), 114.4(CN), 122.2-156.8(Ar-
C), 161.6(C-2), 169.4-169.9(4CO); MS (ionization method): m=z 736(Mþ);
Anal. Calcd for C39H36N4SO9: C, 63.59; H, 4.89; N, 7.61. Found: C, 63.81;
H, 4.97; N, 7.80.
7e:Yield74%,mp118ꢀC;IR2222(CN),1755(CO)cmꢁ 1;1HNMRd1.76-
2.05(4s,4CH3CO), 3.84(s,OCH3),4.02(m,2H-60 andH-50),4.99(t,H-40),5.26(t,
H-30)5.68(t, H-2 0), 6.20(d, J ¼ 10.63 Hz, H-10), 7.18-7.72(m, Ar-H); 13C NMR d
20.2-20.4(4CH3CO), 55.7(OCH3),63.7(C-60),68.8(C-40),72.9(C-20),73.5(C-30),
75.0(C-50), 81.6(C-10), 107.1(C-3), 114.6(CN), 124.4-156.5(Ar-C), 162.8(C-2),
169.4-169.9(4CO); MS (ionization method): m=z 752 (Mþ); Anal. Calcd for
C39H36N4SO10: C, 62.23; H, 4.79; N, 7.45. Found: C, 62.48; H, 4.95; N, 7.73.
1
7f: Yield 71%, mp 128ꢀC; IR 2222(CN), 1751(CO) cmꢁ 1; H NMR d
1.77-2.09(4s, 4CH3CO), 4.08(m, 2H-60), 4.56(m, H-50), 5.30(t, H-40), 5.44(d,
H-30), 5.64(d, H-20)6.21(d, J ¼ 10.84 Hz, H-10), 7.24-8.03(m, Ar-H); 13C
NMR d 20.3-20.5(4CH3CO), 61.9(C-60), 66.7(C-40), 67.8(C-20), 70.8(C-30),
74.4(C-50), 80.7(C-10), 107.4(C-3), 115.1(CN), 131.9-157.0(Ar-C), 161.9(C-2),
169.4-170.0(4CO); MS (ionization method): m=z 722 (Mþ); Anal. Calcd

214
ATTIA
for C38H34N4SO9: C, 63.16; H, 4.71; N, 7.76. Found: C, 63.38; H, 4.93;
N, 7.99.
7g: Yield 68%, mp 150ꢀC; IR 2210(CN), 1748(CO) cmꢁ 1; MS (ioni-
zation method): m=z 801 (Mþ); Anal. Calcd for C38H33N4BrSO9: C, 56.93;
H, 4.12; N, 6.99. Found: C, 57.11; H, 4.30; N, 7.19.
7h: Yield 70%, mp 138ꢀC; IR 2220(CN), 1746(CO) cmꢁ 1; MS (ioni-
zation method): m=z 756 (Mþ); Anal. Calcd for C38H33N4ClSO9: C, 60.28;
H, 4.36; N, 7.40. Found: C, 60.51; H, 4.48; N, 7.66.
1
7i: Yield 73%, mp 112ꢀC; IR 2222(CN), 1748(CO) cmꢁ 1; H NMR d
1.74-2.12(4s, 4CH3CO), 2.28(s, CH3), 4.05(m, 2H-60), 4.37(m, H-50), 5.28(t,
H-40), 5.40(d, H-30), 5.62(d, H-20), 6.18(d, J ¼ 10.81 Hz, H-10), 7.16-8.12(m,
13
Ar-H); C NMR d 20.2-20.5(4CH3CO), 21.1(CH3), 61.2(C-60), 68.4(C-40),
69.8(C-20), 70.8(C-30), 74.3(C-50), 80.7(C-10), 107.3(C-3), 115.2(CN), 122.0-
156.2(Ar-C), 162.4(C-2), 169.4-170.0(4CO); MS (ionization method): m=z
736 (Mþ); Anal. Calcd for C39H36N4SO9: C, 63.59; H, 4.89; N, 7.61. Found:
C, 63.84; H, 5.00; N, 7.77.
1
7j: Yield 72%, mp 120ꢀC; IR 2224(CN), 1749(CO) cmꢁ 1; H NMR d
1.90-2.05(4s, 4CH3CO), 3.82(s, OCH3), 4.04(m, 2H-60), 4.28(m, H-50), 5.26(t,
H-40), 5.56(d, H-30), 5.68(d, H-20), 6.16(d, J ¼ 10.34 Hz, H-10), 7.20-7.79(m,
13
Ar-H); C NMR d 20.2-20.6(4CH3CO), 55.5(OCH3), 62.8(C-60), 68.2(C-40),
70.8(C-20), 78.9(C-30), 79.4(C-50), 81.8(C-10), 107.5(C-3), 114.9 (CN), 124.2-
158.6(Ar-C), 162.8(C-2), 169.2-169.9(4CO); MS (ionization method): m=z
752 (Mþ); Anal. Calcd for C39H36N4SO10: C, 62.23; H, 4.79; N, 7.45. Found:
C, 62.56; H, 4.92; N, 7.60.
3-Cyano-2-(b-D-glycopyranosylthio)pyridines (10).
General procedure for nucleoside deacylation: Dry ammonia gas was
passed into a solution of protected nucleosides 7 (0.5 g)in 20 mL of dry
methanol at 0ꢀC for 0.5 h. The reaction mixture was stirred until
completion as shown by TLC (10–12 h), using chloroform:Methanol 19:1,
n:n, (Rf 0.60-62 region). The resulting mixture was then concentrated
under reduced pressure at 40ꢀC to afford a solid residue that was
crystallized from methanol to furnish the products 10a-j.
10a: Yield 84%, mp 203ꢀC; IR 3370(OH), 2222(CN) cmꢁ 1; 1H NMR d
3.15-3.82(m, 2H-60, H-50, H-40, H-30 and H-20), 4.62(d, 20-OH), 4.75(s, 30-
OH), 5.14(d, 40-OH), 5.29(d, 60-OH), 5.63(d, J ¼ 9.34 Hz, H-10), 7.25-7.64(m,
13
Ar-H); C NMR d 61.0(C-60), 69.8(C-40), 71.5(C-20), 78.5(C-30), 82.0(C-50),
83.8(C-10), 106.7(C-3), 114.6(CN), 121.9-153.8(Ar-C), 159.6(C-2); MS
(ionization method): m=z 554 (Mþ); Anal. Calcd for C30H26N4SO5: C, 64.98;
H, 4.69; N, 10.11. Found: C, 65.33; H, 4.82; N, 10.40.
10b: Yield 83%, mp 196ꢀC; IR 3380(OH), 2215(CN) cmꢁ 1; MS (ioni-
zation method): m=z 633 (Mþ); Anal. Calcd for C30H25N4BrSO5: C, 56.87;
H, 3.95; N, 8.85. Found: C, 57.19; H, 4.14; N, 9.09.

S-GLYCOSYLATED PYRIDINES
215
10c: Yield 80%, mp 204ꢀC; IR 3370(OH), 2220(CN) cmꢁ 1; 1H NMR d
3.18-3.76(m, 2H-60, H-50, H-40, H-30 and H-20), 4.64(d, 20-OH), 5.15(d, 30-
OH), 5.30(d, 40-OH), 5.52(d, 60-OH), 5.96(d, J ¼ 8.98 Hz, H-10), 7.26-8.00(m,
13
Ar-H); C NMR d 61.6(C-60), 69.9(C-40), 72.0(C-20), 78.2(C-30), 81.8(C-50),
83.4(C-10), 106.8(C-3), 116.6(CN), 123.2-153.9(Ar-C), 159.9(C-2); MS (ioni-
zation method): m=z 588 (Mþ); Anal. Calcd for C30H25N4ClSO5: C, 61.17;
H, 4.25; N, 9.51. Found: C, 61.50; H, 4.41; N, 9.77.
10d: Yield 85%, mp 193ꢀC; IR 3370(OH), 2222(CN) cmꢁ 1; 1H NMR d
2.30(s, CH3), 3.32-3.78(m, 2H-60, H-50, H-40, H-30 and H-20), 4.64(d, 20-OH),
5.06(d, 30-OH), 5.14(d, 40-OH), 5.28(d, 60-OH), 5.62(d, J ¼ 8.83 Hz, H-10),
7.12-7.90(m, Ar-H); 13C NMR d 21.0(CH3), 61.9(C-60), 69.8(C-40), 71.5(C-20),
78.5(C-30), 81.9(C-50), 83.8(C-10), 106.6(C-3), 115.2(CN), 122.0-153.6(Ar-C),
159.8(C-2); MS (ionization method): m=z 568 (Mþ); Anal. Calcd for
C31H28N4SO5: C, 65.49; H, 4.93; N, 9.86. Found: C, 65.68; H, 5.12; N, 10.09.
10e: Yield 86%, mp 180ꢀC; IR 3360(OH), 2210(CN) cmꢁ 1; 1H NMR d
3.20-3.84(m, 2H-60, H-50, H-40, H-30 and H-20), 3.84(s, OCH3), 4.63(d, 20-OH),
4.78(s, 30-OH), 5.13(d, 40-OH), 5.27(d, 60-OH), 5.68(d, J ¼ 9.70 Hz, H-10), 7.20-
13
7.79(m, Ar-H); C NMR d 55.6(OCH3), 61.0(C-60), 69.8(C-40), 71.5(C-20),
78.5(C-30), 81.9(C-50), 83.8(C-10), 106.6(C-3), 114.6(CN), 124.3-158.0(Ar-C),
162.7(C-2); MS (ionization method): m=z 584 (Mþ); Anal. Calcd for
C31H28N4SO6: C, 63.70; H, 4.79; N, 9.59. Found: C, 64.07; H, 4.93; N, 9.81.
10f: Yield 85%, mp 189ꢀC; IR 3360(OH), 2222(CN) cmꢁ 1; 1H NMR d
3.36-3.84(m, 2H-60, H-50, H-40, H-30 and H-20), 4.62(d, 20-OH), 4.78(s, 30-
OH), 5.06(s, 20-OH), 5.40(d, 60-OH), 5.64(d, J ¼ 10.27 Hz, H-10), 7.12-8.14(m,
13
Ar-H); C NMR d 60.8(C-60), 63.7(C-40), 68.6(C-20), 74.8(C-30), 80.1(C-50),
84.3(C-10), 106.7(C-3), 115.1(CN), 121.9-158.3(Ar-C), 161.9(C-2); MS (ioni-
zation method): m=z 554 (Mþ); Anal. Calcd for C30H26N4SO5: C, 64.98; H,
4.69; N, 10.11. Found: C, 65.30; H, 4.86; N, 10.29.
10g: Yield 81%, mp 205ꢀC; IR 3360(OH), 2210(CN) cmꢁ 1; MS (ioni-
zation method): m=z 633 (Mþ); Anal. Calcd for C30H25N4BrSO5: C, 56.87;
H, 3.95; N, 8.85. Found: C, 57.10; H, 4.13; N, 8.99.
10h: Yield 83%, mp 200ꢀC; IR 3370(OH), 2218(CN) cmꢁ 1; MS (ioni-
zation method): m=z 588 (Mþ); Anal. Calcd for C30H25N4ClSO5 C, 61.17; H,
4.25; N, 9.51. Found: C, 61.39; H, 4.36; N, 9.69.
10i: Yield 82%, mp 208ꢀC; IR 3360(OH), 2220 (CN) cmꢁ 1; 1H NMR d
2.31(s, CH3), 3.32-3.83(m, 2H-60, H-50, H-40, H-30 and H-20), 4.61(d, 20-OH),
4.79(s, 30-OH), 5.06(s, 40-OH), 5.45(d, 60-OH), 5.63(d, J ¼ 10.45 Hz, H-10),
7.19-8.10(m, Ar-H); 13C NMR d 21.0(CH3), 60.8(C-60), 68.5(C-40), 68.7(C-20),
74.9(C-30), 80.2(C-50), 84.3(C-10), 106.6(C-3), 115.2(CN), 122.0-158.5(Ar-C),
161.8(C-2); MS (ionization method): m=z 568 (Mþ); Anal. Calcd for
C31H28N4SO5: C, 65.49; H, 4.93; N, 9.86. Found: C, 65.70; H, 5.05; N, 10.03.
10j: Yield 84%, mp 198ꢀC; IR 3350(OH), 2222(CN) cmꢁ 1; MS (ioni-
zation method): m=z 584 (Mþ); Anal. Calcd for C31H28N4SO6: C, 63.70; H,
4.79; N, 9.59. Found: C, 63.95; H, 4.88; N, 9.73.

216
ATTIA
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Received April 11, 2001
Accepted December 26, 2001