Glycosylation Reaction of Unprotected Sugars with Hydroxyalkylthymine

Abstract

Under mild conditions (Lewis acid/solvent/room temperature), the reaction of unprotected glucose, deoxyribose or xylose with hydroxylalkylthymine gives selectively nucleoside analogs with a spacer arm between sugar and base moiety. Experimental conditions (Lewis acid, solvent) for this new strategy leading to nucleoside analogs synthesis are discussed.

Keywords:

• Nucleoside
• Carbohydrate
• Glycosylation

Notes

^aSelected values of ¹H NMR for acetylated derivatives of 2a (α) and 3 compound 2a (α) : thymine: 8.98 s (1H) NH, 7.01 q (1.2) (1H) H6, 1.91 d (1.2) (3H) CH₃, alkyl : 3.74 t (7.1) (2H) Hα, 1.78 m (2H) Hβ, 1.65 dt (6.1) (2H) Hγ, 3.91 dt (6.1) (1H)Hδ1, 3.49 dt (6.1) (1H) Hδ2 carbohydrate : 4.51 dd (5.4–5.3) (1H) H1′, 2.0 dd (2.9–8.4) (1H) H2′, 2.0 dd (2.9–6.7) (1H) H2″, 5.03 ddd (3.2–7.8–6.4) (1H) H3′, 5.08 ddd (1.9–3.4–3.4) (1H) H4′, 4.04 dd (12.9–3.6) (1H) H5′, 3.57 dd (12.9–1.9) (1H) H5′, CH₃ acetyl : 2.12 s, 2.08 s, 2.03 s, 2.01 s (12H). Compound 3 : thymine : 8.81 s (1H) NH, 7.01 d (1.1) (1H) H6, 1.93 d (1.1) (3H) CH₃, alkyl : 3.76 t (7.2) (1H) Hα, 1.81 m (2H) Hβ, 1.66 m (2H) γ, 3.72 m (1H) Hδ1, 3.49 dt (5.8) (1H) Hδ2, carbohydrate : 4.98 s (1H) H1′, 4.98 s (1H) H2′, 5.3 d (5.1) (1H).H3′, 4.48 dd (5.1–9.4) (1H) H4′, 5.28 ddd (2.3–5.6–9.4) (1H) H5′, 4.64 dd (2.3–12.2) (1H) H6′, 4.11 dd (5.6–12.2) (1H) H6′, CH3 acetyl : 2.12 s, 2.08 s, 2.03 s, 2.01 s (12H).