1000
Pierra, Amador, Badaroux, Storer, Gosselin:
(M – H)–, 111 (B)–. 1H NMR (200 MHz, DMSO-d6): 11.40 s, 1 H, D2O exch an geable (NH);
8.08 d, 1 H, J(6,5) = 8.1 (H-6); 6.18 an d 5.82 2s, 1 H (H-1′); 5.62 2d, 1 H, J(5,6) = 8.1 (H-5);
5.3–4.9 2m , 3 H, 2 sign als D2O exch an geable (OH-3′, OH-5′, CH); 3.9–3.5 m , 6 H (H-5′a,
H-5′b, H-4′, H-3′, CH2); 1.5 m , 6 H (3 CH2); 1.13 s, 3 H (CH3).
5′-O-(tert-Butyldim eth ylsilyl)-2′-C-m eth yl-2′-O-(tetrah ydropyran -2-yl)uridin e (5)
To a stirred solution of com poun d 4 (4.65 g, 13.6 m m ol) an d tert-butyldim eth ylsilyl ch loride
(2.20 g, 15.0 m m ol) in dry pyridin e (100 m l) was added im idazole (1.40 g, 20.4 m m ol), an d
th e m ixture was stirred at room tem perature for 2 h . Th e reaction profile was followed by
TLC an d th e reaction m ixture was rech arged with tert-butyldim eth ylsilyl ch loride (0.82 g,
4.80 m m ol an d 1.13 g, 6.80 m m ol) an d im idazole (0.55 g, 8.16 m m ol). After 2 h , th e reac-
tion was still in com plete. It was rech arged with addition al tert-butyldim eth ylsilyl ch loride
(1.13 g, 6.80 m m ol) an d im idazole (0.70 g, 10.2 m m ol). An aqueous solution of NaHCO3
was th en slowly added an d th e resultin g m ixture was extracted with eth yl acetate. Th e or-
gan ic ph ase was wash ed with water, dried over an h ydrous sodium sulfate, an d evaporated
un der pressure. Th e crude m ixture was purified by silica gel colum n ch rom atograph y
(eluen t: dieth yl eth er, 50–70% in petroleum eth er) to afford th e title com poun d 5 as a
diastereoisom eric m ixture (5.06 g, 82%). FAB positive, m/z (GT): 913 (2 M + H)+, 549 (M +
G + H)+, 457 (M + H)+, 373 (M – THP + 2 H)+, 345 (M – B)+, 113 (B + 2 H)+, 85 (THP)+;
FAB n egative, m/z (GT): 911 (2 M – H)–, 547 (M + G – H)–, 455 (M – H)–, 111 (B)–. 1H NMR
(250 MHz, DMSO-d6): 11.43 s, 1 H, D2O exch an geable (NH); 7.91 d, 1 H, J(6,5) = 8.1 (H-6);
6.16 an d 5.80 2s, 1 H (H-1′); 5.49 2d, 1 H, J(5,6) = 8.1 (H-5); 5.24 an d 5.04 2d, 1 H, D2O
exch an geable (OH-3′), 5.1 m , 1 H (CH); 4.1–3.5 m , 6 H (H-5′a, H-5′b, H-4′, H-3′, CH2);
1.9–1.3 m , 6 H (3 CH2); 1.07 2s, 3 H (CH3); 0.88 s, 9 H ((CH3)3C); 0.08 s, 6 H (Si(CH3)2).
3′-Deoxy-2′-C-m eth yluridin e (6) an d 2′,3′-Dideoxy-2′-C-m eth yluridin e (7)
To a solution of in term ediate 5 (1.20 g, 2.63 m m ol) in dry aceton itrile (24 m l), were succes-
sively added O-ph en yl ch loroth ioform ate (0.49 m l, 3.55 m m ol) an d 4-(dim eth ylam in o)pyri-
din e (800 m g, 6.57 m m ol), an d th e reaction m ixture was stirred at room tem perature
overn igh t. After evaporation of th e solven t, th e residue was diluted with eth yl acetate an d
wash ed with water. Th e organ ic ph ase was dried over an h ydrous sodium sulfate an d evapo-
rated to dryn ess. Th e residue was dissolved in an h ydrous toluen e (30 m l) an d refluxed with
2,2′-azoisobutyron itrile (130 m g, 0.79 m m ol) an d tris(trim eth ylsilyl)silan e (1.2 m l, 3.95 m m ol).
After rem oval of th e solven t, th e crude m ixture was taken up in a m ixture of acetic acid–
tetrah ydrofuran –water (4:2:1, 160 m l) an d stirred at room tem perature for 2 days. After
evaporation of th e solven ts an d coevaporation with toluen e, th e crude m ixture was purified
by silica gel colum n ch rom atograph y (eluen t: m eth an ol, 0–6% in m eth ylen e ch loride) to
isolate 3′-deoxy-2′-C-m eth yluridin e 6 (141 m g, 22%) alon g with a less polar side product
2′,3′-dideoxy-2′-C-m eth yluridin e 7 (116 m g, 56%). Th e desired product 6 was crystallized
from m eth an ol–ch loroform , m .p. 197–199 °C. For C10H14N2O5·0.4H2O (249.4) calculated:
48.15% C, 5.98% H, 11.23% N; foun d: 48.28% C, 5.69% H, 11.06% N. FAB positive, m/z
(GT): 485 (2 M + H)+, 335 (M + G + H)+, 243 (M + H)+, 131 (M – B)+, 113 (B + 2 H)+; FAB
n egative, m/z (GT): 483 (2 M – H)–, 333 (M + G – H)–, 241 (M – H)–, 111 (B)–. 1H NMR
(250 MHz, DMSO-d6): 11.32 s, 1 H, D2O exch an geable (NH); 8.13 d, 1 H, J(6,5) = 8.1 (H-6);
5.77 s, 1 H (H-1′); 5.59 d, 1 H, J(5,6) = 8.1 (H-5); 5.44 s, 1 H, D2O exch an geable (OH-2′);
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 7, pp. 991–1010