Purine → 1-O-methyl 5-(t-butyldiphenylsilyl)-beta-D-ribofuranoside

Beteiligte Stoffe

Reaktionsschritte

The triple substitution of adenosine, i.e., at 5'-, 2-, and N6 -positions, can be carried out by a synthetic strategy in which a 5'-uronamide sugar moiety is condensed with a purine moiety, such as a substituted adenosine derivative. The key sugar intermediate, N-methyl 1-O-acetyl-2,3-dibenzoyl-β-D-ribofuronamide, was synthesized starting from methyl β-D-ribofuranoside, which is commercially available or can be synthesized from D-ribose (Baker et al., J. Org. Chem., 26, 4605-4609 (1961)), in 8 steps. The primary alcohol of β-D-ribofuranoside can be selectively protected with tert-butyldiphenylsilyl chloride (Chaudhary et al., Tet. Lett., 20(2), 99-102 (1979)) to provide 1-O-methyl 5-(t-butyldiphenylsilyl)-β-D-ribofuranoside, and other alcohols can be followed with benzoyl protection to provide 1-O-methyl 5-(t-butyldiphenylsilyl)-2,3-dibenzoyl-β-D-ribofuranoside, the desilylation of which with TBAF/THF will give 1-O-methyl 2,3-dibenzoyl-β-D-ribofuranoside. The 5'-position of 1-O-methyl 2,3-dibenzoyl-β-D-ribofuranoside can be oxidized using ruthenium tetroxide (Singh et al., Tet. Lett., 33(17), 2307-2310 (1992)) to yield 1-O-methyl-2,3-dibenzoyl-β-D-ribofuronic acid which can be purified after methylation on a silica gel column chromatography. Methylamide at 5-position can be introduced by nucleophilic displacement of methyl 1-O-methyl-2,3-dibenzoyl-β-D-ribofuronate with methylamine in THF and benzoyl reprotection of resulting 2,3-diol to yield the sugar intermediate N-methyl 1-O-acetyl-2,3-dibenzoyl-β-D-ribofuronamide.

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