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

HRID 965182

Reaktionsgleichung

Reaktionsgleichung von HRID 965182
N1C=C2C(N=CN2)=NC=1.[O:10]([CH3:20])[C@@H:11]1[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]1[OH:13].O=C[C@@H]([C@@H]([C@@H](CO)O)O)O.CC1C(=O)NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C=1.[Si:49](Cl)([C:62]([CH3:65])([CH3:64])[CH3:63])([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>>[Si:49]([CH:18]([OH:19])[C@H:16]1[O:17][C@@H:11]([O:10][CH3:20])[C@H:12]([OH:13])[C@@H:14]1[OH:15])([C:62]([CH3:65])([CH3:64])[CH3:63])([C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Komponenten

6

Edukt 5

HCID 1044PurineHCID 81983Methyl beta-D-ribofuranosideHCID 94078tert-ButyldiphenylchlorosilaneHCID 4454085-MethyluridineHCID 5311110Aldehydo-D-ribose

Produkt 1

HCID 186611941-O-methyl 5-(t-butyldiphenylsilyl)-beta-D-ribofuranoside

Versuchsvorschrift

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.

Quellen und Nachweise

ORD-Eintrag
ord-edea81be179045ca9e8556c89cec8c62
Quelldatensatz
uspto-grants-1998_06
Patentnummer
US05773423

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