9-[(4氟-)-3羟-基甲基丁基]鸟嘌呤(FHBG)的改进合成方法

The Improved Synthesis of 9-[(4-Fluoro)-3-hydroxymethylbutyl] Guanine(FHBG)

报道了9-[(4氟-)-3羟-基甲基丁基]鸟嘌呤(FHBG,Ⅱ)的改进合成方法,对起始原料喷昔洛韦(Ⅲ)的氨基和一个羟基用4-甲氧基氯化三苯甲烷保护,对另一个羟基磺酯化,得到N2-(p-甲氧基苯酰基二苯基甲基)-9-[(4甲-苯磺酰)-3-p-甲氧基苯酰基二苯基-甲氧基甲基丁基]鸟嘌呤(Ⅴ),收率为70.5%;再用四丁基氟化铵(TBAF)对化合物Ⅴ亲核取代4-甲苯磺酰基团,水解脱去保护基,即得FHBG。产品经1HNMR、IR、MS表征,并用HPLC分析了Ⅴ和Ⅱ,保留时间分别为5.89 m in和4.41 m in,积分计算质量分数分别为w(Ⅴ)=99.5%和w(Ⅱ)=99.3%。

The improved synthesis of 9- [ （ 4-fluoro ） -3-hydroxymethylbutyl ] guanine （ FHBG, Ⅱ ） is reported. Penciclovir （ Ⅲ ） was converted to ditrityl-penciclovir （ Ⅳ ） by treatment with methoxytrityl chloride. Ⅳ was transformed to ditrityl-4-tosyl-penciclovir （Ⅴ ） by tosylation with high yield （ up to 70. 5% ）. V reacted with tetrabutylammonium fluoride to afford ditrityl-4-fluoro-penciclovir （Ⅵ）. Removal of the methoxytrityl groups in VI by acidic hydrolysis produced Ⅱ. Structures of the products were characterized by IR, ^1HNMR spectra and MS. For the quality control, Ⅱ and Ⅴ were analyzed by HPLC on a reverse-phase C18 column ,eluting at 5.89 min and 4. 41 min respectively ,to give w（ Ⅱ ） = 99.5% and w（V） =99.3% by HPLC area normalization method.