替诺福韦-阿拉芬酰胺
替诺福韦
化学
前药
催化作用
产量(工程)
组合化学
有机化学
人类免疫缺陷病毒(HIV)
病毒学
生物化学
医学
材料科学
病毒载量
冶金
抗逆转录病毒疗法
作者
Hangzhou Shen,Yingshuai Liu,Xiaomeng Tian,Yinsheng Zhang,Yinsheng Zhang
标识
DOI:10.1002/slct.201801990
摘要
Abstract To support clinical bioequivalence (BE) studies of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF), both deuterium‐labeled TDF and TAF (or their free bases, TD & TA) are highly desired for use as an internal standard. We have developed a method to prepare racemic [D 8 ]9‐(2‐hydroxypropyl)adenine (racemic R/S‐HPA) using a 10%Pd/C & PtO 2 catalyzed H−D exchange reaction as the key step to introduce the label in a highly efficient and cost‐effective way. The labeled R/S‐HPA was converted to racemic [D 8 ]9‐[2‐phosphonomethoxypropyl]adenine ([D 8 ] R/S‐PMPA) in two steps. Using [D 8 ] R/S‐PMPA as a common intermediate, thus, we further synthesized [D 8 ] R/S‐tenofovir disoproxil fumarate and [D 8 ]tenofovir alafenamide in 2–3 steps with 60% and 20% overall yield, respectively.
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