Patent GB-1101233-A (GB)
Title: Process for preparing nucleotide derivatives
IPC: C07H19/10
Filed: 1965-08-09
Abstract: Silicon containing derivatives of purine and pyrimidine bases are obtained by reacting a purine or pyrimidine base of the formula <FORM:1101233/C3/1> <FORM:1101233/C3/2> where R1 and R2 represent H, OH or an acylamino group and each of R3 and R4 represent H, OH, an amino group, a C1- 5 alkoxy group or a methyl group, with a tri-(C1- 5-alkyl)-chlorosilane in the presence of a tertiary amine or with a hexa-(C1- 5-alkyl)-disilazane under anhydrous conditions.  The process employing a tri-(C1- 5-alkyl) -chlorosilane may suitably be effected at room temperature in an anhydrous organic solvent, e.g. benzene, toluene, a xylene or dioxan, and suitable tertiary amines are tri-C1- 5-alkylamines such as trimethyl-, triethyl- or tripropyl-amine and cyclic tertiary amines, e.g. pyridine.  When a hexa-(C1- 5-alkyl)-disilazane is employed the reaction is preferably effected by suspending the corresponding purine or pyrimidine base in the disilazane and heating the resulting suspension under reflux. Specified silyl derivatives are bistrimethylsilylthyanine, bistrimethylsilyluracil, bistrimethylsilyl-N-benzoyladenine, bistrimethylsilylhypoxanthine, 9-trimethylsilyltheophyline, trimethylsilyl - 1,2 -dihydro - 2 - keto - 4 - ethoxy - pyrmidine and bistrimethylsilyluracil.ALSO:Compounds having the formulae <FORM:1101233/C2/1> <FORM:1101233/C2/2> wherein each of R1 and R2 represents a hydrogen atom, a hydroxy group or an acylamino group, each of R3 and R4 represents a hydrogen atom, a hydroxy group, an amino group, a C1- 5 alkoxy group or a methyl group and Y represents a phosphorylated glycosyl radical containing protected hydroxy groups and a protected phosphoric acid group, are prepared by reacting the appropriate purine or pyrimidine base with a tri-(C1- 5-alkyl) chlorosilane in the presence of a tertiary amine or with a hexa- (C1- 5-alkyl) disilazane under anhydrous conditions and heating the resulting product with a compound selected from phosphorylated halogeno-pentoses and phosphorylated halogeno-hexoses containing protected hydroxy groups and a protected phosphoric acid group at 80 DEG  to 120 DEG  C.  The process employing a tri-(C1- 5 alkyl)-chlorosilane may generally be effected at room temperature in an anhydrous organic solvent, e.g. benzene, toluene, a xylene or dioxan and suitable tertiary amines are tri-C1- 5-alkyl-amines such as trimethyl-, triethyl- or tripropylamines, and cyclic tertiary amines, e.g. pyridine.  When a hexa-(C1- 5 alkyl)-disilazane is employed in the process the reaction is preferably effected by suspending the corresponding purine or pyrimidine base in the hexa-C1- 5-alkyl)- disilazane and heating the resultant suspension under reflux.  The resultant silicon-containing product is then heated with a phosphorylated halogeno-pentose or -hexose, e.g. 2,3,4-o-acetyl (or benzoyl)-6-diphenyl (or p-nitrophenyl or benzyl) phosphoryl-o-glucopyranosyl-halogenide or 2,3-di-o-acetyl- (or benzoyl)-5-di-phenyl (or p-nitrophenyl or benzyl) phosphoryl-o-ribofuranosyl-halogenide, optionally under an inert atmosphere, e.g. nitrogen. The protected nucleotide products may be recovered by conventional means and may subsequently be converted to the corresponding unprotected nucleotides by hydrolysis in the case of pyrimidine nucleotides or by treatment with an alkali metal hydroxide and an alkali metal methoxide followed by treatment with phosphodiesterase in the case of purine nucleotides.