An effective reagent to functionalize alcohols with phosphocholine
An effective reagent to functionalize alcohols with phosphocholine
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DOI：
10.1039/c9ob02582k
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发表时间：
2020-01-28
影响因子：
3.2
通讯作者：
Townsend, Steven D.
中科院分区：
文献类型：
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作者：
Xu, Lianyan L.;Berg, Lawrence J.;Townsend, Steven D.
磷酸胆碱是一种小半抗原分子，既是胆碱的前体，也是胆碱的降解产物。磷酸胆碱装饰许多生物制品，例如脂质和寡糖。在这项研究中，开发了一种空气和工作台稳定的磷酸胆碱供体，并用许多酒精受体进行了评估。使用一锅三步序列（磷酸化、氧化和磷酸盐脱保护）以高产率合成磷酸胆碱衍生物。特别令人感兴趣的是米替福辛的合成，这是唯一被批准用于治疗利什曼病的口服药物。由于其昂贵的价格（每克 1500 美元），世界上大多数患者都无法获得米替福辛。根据所描述的反应顺序，该药物的生产价格为每克 25 美元。
Phosphocholine is a small haptenic molecule that is both a precursor and degradation product of choline. Phosphocholine decorates a number of biologics such as lipids and oligosaccharides. In this study, an air and bench stable phosphocholine donor has been developed and evaluated with a number of alcohol acceptors. Using a one-pot, three-step sequence, (phosphitylation, oxidation, and phosphate deprotection) phosphocholine derivatives are synthesized in high yields. Of particular interest is the synthesis of miltefosine, the lone oral drug approved to treat leishmaniasis. Due to its prohibitive expense ($1500 per g), miltefosine is not accesable for the majority of the world's patients. Based on the described reaction sequence, this drug can be produced for $25 per g.