Convenient synthesis of nucleoside borane diphosphate analogues: deoxy- and ribonucleoside 5'-P(alpha)-boranodiphosphates.
Convenient synthesis of nucleoside borane diphosphate analogues: deoxy- and ribonucleoside 5'-P(alpha)-boranodiphosphates.
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方便合成核苷硼烷二磷酸类似物：脱氧核苷和核糖核苷 5-P(α)-硼烷二磷酸。
DOI：
10.1021/jo049094b
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Shaw,BarbaraRamsay
中科院分区：
文献类型：
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作者：
Li,Ping;Shaw,BarbaraRamsay
核苷硼磷酸，具有一个非桥磷酸氧取代的硼烷（BH 3）基团，已显示出潜在的治疗应用作为适体，反义剂，和抗病毒前药。一种不需要环外胺保护的氧硫磷杂环戊烷方法已被成功地开发用于有效地合成2 '-脱氧胸苷、腺苷、鸟苷和尿苷的5'-Pα-硼二磷酸。该方法涉及一个关键中间体，即核苷5 '-O-1，3，2-氧硫杂磷杂环戊烷的硼烷复合物16，该复合物在1，4-二氮杂双环[5.4.0]-十一碳-7-烯催化下发生开环反应，形成受保护的核苷5'-Pα-硼二磷酸盐18。用氢氧化铵处理18得到核苷5 '-Pα-硼二磷酸盐的非对映异构体混合物5。这种氧硫磷杂环戊烷方法确保了抗病毒药物研究所需的核苷5 '-Pα-硼二磷酸类似物的可用性。
The nucleoside boranophosphates, having one of the nonbridging phosphate oxygens substituted with a borane (BH3) group, have shown potential therapeutical applications as aptamers, antisense agents, and antiviral prodrugs. An oxathiaphospholane approach, which does not require exocyclic amine protection of the nucleobase, has been successfully developed to efficiently synthesize 5‘-Pα-boranodiphosphates of 2‘-deoxythymidine, adenosine, guanosine, and uridine. The approach involves a key intermediate, the borane complex of nucleoside 5‘-O-1,3,2-oxathiaphospholane16, that undergoes a ring-opening reaction catalyzed by 1,4-diazabicyclo[5.4.0]-undec-7-ene to form the protected nucleoside 5‘-Pα-boranodiphosphate18. Treatment of18with ammonium hydroxide yielded diastereoisomeric mixtures of nucleoside 5‘-Pα-boranodiphosphates5. This oxathiaphospholane approach ensures the availability of nucleoside 5‘-Pα-boranodiphosphate analogues needed for antiviral drug research.