6-氯和6-甲氧基嘌呤核苷的合成

以四乙酰呋喃核糖(Ⅰ)和6 氯嘌呤(Ⅱ)为原料,在对甲苯磺酸(TsOH)存在下,运用微波固态反应得到中间体2′,3′,5′ 三乙酰基 6 氯嘌呤核苷(Ⅲ),收率为80 1%。该中间体再用NH3/CH3OH和Na2CO3/CH3OH处理,分别合成了6 氯 9 β D 嘌呤核苷(Ⅳ)和6 甲氧基 9 β D 嘌呤核苷(Ⅴ),收率分别为78 8%和76 9%。Ⅳ和Ⅴ的总收率分别为63 1%和61 6%,结构经1HNMR和元素分析证实。最佳的缩合条件是n(Ⅰ)∶n(Ⅱ)=1∶1,m(TsOH)/m(6 氯嘌呤)=0 03,595W微波辐射4 5min,462W微波辐射1min和119W微波辐射0 5min;生成Ⅳ的氨解条件为室温反应2h,生成Ⅴ的碱解条件为回流5h。

Synthesis of 6-Chloro-and 6-Methoxypurinenucleoside

Starting from tetraacetylribofuranose(Ⅰ) and 6-chloropurine(Ⅱ),in the presence of p-toluenesulfonic acid as catalyst,the intermediate 2′,3′,5′-tri-O-acetyl-6-chloropurinenucleoside(Ⅲ) was obtained by condensation under microwave irradiation in 80.1% yield.Treating Ⅲ with NH_3/CH_3OH or Na_2CO_3/CH_3OH gave the title compound 6-chloro-9-β-D-purinenucleoside (Ⅳ) or 6-methoxy-9-β-D-purinenucleoside (Ⅴ) in 78.8% or 76.9% yield respectively.Structures of the products were identified by ~1HNMR and elementary analysis.The optimal conditions for condensation reaction were n(Ⅰ)/n(Ⅱ)=1,m(TsOH)/m(Ⅱ)=0.03,microwave irradiation at 595 W for 5 min,at 462 W for 1 min and then at 119 W for 0.5 min.Aminolysis for Ⅳ was carried out at room temperature for 2 h.Alkaline hydrolysis for Ⅴ was performed by refluxing for 5 h.