984
Adams, Bats, Nikolaus, Witvrouw, Debyser, Engels:
for 1 h , n eutralized with Dowex 50WX8, filtered, wash ed with m eth an ol an d th e solven t
was evaporated in vacuo. Th e products were reprecipitated from m eth an ol.
8-Fluoro-1-(β-D-ribofuranosyl)quinolin-4(1H)-one (8a). 8-Fluoro-1-(2,3,5-tri-O-acetyl-β-D-ribo-
furan osyl)quin olin -4(1H)-on e (6a; 0.5 g, 1.19 m m ol), dry m eth an ol (9 m l) an d th e sodium
m eth oxide solution (0.06 m l) were reacted accordin g to th e gen eral procedure. Yield 0.24 g
(68%). RF 0.48 (CH2Cl2–MeOH 4:1). 1H NMR (250 MHz, DMSO-d6): 8.32 (d, J = 8.25, 1 H,
H2); 8.08 (m , 1 H, H7); 7.59 (m , 1 H, H5); 7.36 (m , 1 H, H6); 6.10 (d, J = 9.25, 1 H, H3);
5.70 (m , 2 H, H1′, 2′-OH); 5.22 (d, J = 5.25, 1 H, 3′-OH); 5.18 (d, J = 5, 1 H 5′-OH); 4.11 (m ,
1 H, H2′); 3.90 (m , 1 H, H3′); 3.84 (m , 1 H, H4′); 3.70 (m , 2 H, H5′a, H5′b). 13C NMR
(63 MHz, DMSO-d6): 175.61 (C4), 169.71 (C-F), 169.18 (C9), 140.71 (C2), 128.91 (C7),
123.21 (C10), 110.55 (C6), 107.96 (C3), 103.43 (C5), 91.33 (C1′), 85.29 (C4′), 73.66 (C2′),
62.07 (C3′), 60.06 (C5′). ESI (–), m/z: 292.9 (M – 2 H)2–
.
7-Fluoro-1-(β-D-ribofuranosyl)quinolin-4(1H)-one (8b). 7-Fluoro-1-(2,3,5-tri-O-acetyl-β-D-ribo-
furan osyl)quin olin -4(1H)-on e (6b; 5.9 g, im pure), dry m eth an ol (100 m l) an d th e sodium
m eth oxide solution (0.79 m l) were reacted accordin g to th e gen eral procedure. Th e product
was purified by colum n ch rom atograph y an d reprecipitated from m eth an ol. Yield 1.2 g
(43%). RF 0.47 (CH2Cl2–MeOH 4:1). 1H NMR (250 MHz, DMSO-d6): 8.45 (d, J = 8.25, 1 H,
H2); 8.22 (m , 1 H, H8); 7.66 (m , 1 H, H5); 7.27 (m , 1 H, H6); 6.10 (d, J = 8.25, 1 H, H3);
5.94 (d, J = 4.25, 1 H, H1′); 5,72 (d, J = 6.0, 1 H, 2′-OH); 5.24 (m , 2 H, 3′-OH, 5′-OH); 4.13
(m , 1 H, H2′); 4.02 (m , 2 H, H3′, H4′); 3.66 (m , 2 H, H5′a, H5′b). 13C NMR (63 MHz,
DMSO-d6): 175.95 (C4), 162.61 (C-F), 141.05 (C9), 138.96 (C2), 129.03 (C8), 123.18 (C10),
112.20 (C6), 109.25 (C3), 102.26 (C5), 91.54 (C1′), 85.06 (C4′), 74.59 (C2′), 62.28 (C3′),
60.13 (C5′). MALDI (+), m/z: 296.5 (M + H)+.
6-Fluoro-1-(β-D-ribofuranosyl)quinolin-4(1H)-one (8c). 6-Fluoro-1-(2,3,5-tri-O-acetyl-β-D-ribo-
furan osyl)quin olin -4(1H)-on e (6c; 1.899 g, 4.506 m m ol), dry m eth an ol (35 m l) an d th e so-
dium m eth oxide solution (0.30 m l) were reacted accordin g to th e gen eral procedure. Th e
product was recrystallized from m eth an ol. Yield 1.293 g (97%). RF 0.125 (CH2Cl2–MeOH
9:1). 1H NMR (250 MHz, DMSO-d6): 8.50 (d, J = 8.75, 1 H, H2); 7.84 (m , 2 H, H5, H7); 7.65
(m , 1 H, H8); 6.11 (d, J = 7.75, 1 H, H3); 6.01 (d, J = 4, 1 H, H1′); 4.19 (m , 1 H, H2′); 4.02
(m , 2 H, H4′, H3′); 3.67 (m , 2 H, H5′a, H5′b). 13C NMR (63 MHz, DMSO-d6): 174.87 (C4),
168.89 (C-F), 138.54 (C9), 128.93 (C7), 122.32 (C10), 117.47 (C5), 109.29 (C8), 77.91 (C4′),
71.10 (C2′), 67.82 (C3′), 61.05 (C5′). ESI (+), m/z: 296.0 (M + H)+.
X-ray an alysis of 8c: C14H14FNO5·0.5CH3OH·0.25H2O. Crystal system : m on oclin ic, space
group: P21↑, crystal color: colorless, un it cell param eters: a = 8.0476(12) Å, b = 43.884(7) Å,
c = 8.1096(12) Å, β = 90.432(6)°, V = 2863.9(8) Å3, Z = 8, R = 0.102, GOF = 1.03. A sin gle
crystal was m easured on a Siem en s Sm art CCD diffractom eter, radiation MoKα at tem pera-
ture of ca. –114 °C. Th e structure was determ in ed by direct m eth ods usin g program SHELXS.
CCDC 600092 con tain s th e supplem en tary crystallograph ic data for th is paper. Th ese data
Cam bridge Crystallograph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax:
+44 1223 336033; or deposit@ccdc.cam .ac.uk).
In vitro An ti-HIV Assay an d Drug Susceptibility Assay
Th e an tiviral activity of th ese com poun ds on th e HIV-in duced CPE in h um an lym ph ocyte
MT-4 cell culture was determ in ed by th e MT-4/MTT-assay17. All com poun ds proved to be in -
active again st HIV-1 replication at subtoxic con cen tration s.
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 7, pp. 978–990