使用串联亚磷酰胺法对TLR7/8活性咪唑喹啉进行磷脂化修饰。
Phospholipidation of TLR7/8-active imidazoquinolines using a tandem phosphoramidite method.
作者信息
Bazin Hélène G, Bess Laura S, Livesay Mark T, Mwakwari Sandra C, Johnson David A
机构信息
GSK Vaccines, 553 Old Corvallis Road, Hamilton, MT 59840, USA.
出版信息
Tetrahedron Lett. 2016 May 11;57(19):2063-2066. doi: 10.1016/j.tetlet.2016.03.091. Epub 2016 Apr 1.
Abstract
A high-yielding and scalable phosphoramidite procedure was developed for the phospholipidation of TLR7/8-active imidazoquinolines. This method involves the reaction of a 1,2-diacyl- or dialkyl--glycerol or 3-chlolesterylalkanol with 2-cyanoethyl ,,','-tetraisopropylphosphordiamidite in the presence of -tetrazole followed by treatment of the resulting ,'-diisopropylphosphoramidite lipid in situ with 1-imidazoquinolinylalkanols. The resulting phosphite can be purified or directly oxidized with -butyl hydroperoxide. The cyanoethyl protecting group is then removed with triethylamine and the phospholipidated imidazoquinoline products isolated in good yield and purity by simple filtration.
摘要
开发了一种高产且可扩展的亚磷酰胺方法用于TLR7/8活性咪唑喹啉的磷脂化。该方法包括在四唑存在下，使1,2-二酰基或二烷基甘油或3-胆固醇基链烷醇与2-氰基乙基四异丙基亚磷二酰胺反应，然后用1-咪唑喹啉基链烷醇原位处理所得的'-二异丙基亚磷酰胺脂质。所得的亚磷酸酯可以纯化或直接用过氧化叔丁基氧化。然后用三乙胺除去氰基乙基保护基，并通过简单过滤以良好的产率和纯度分离出磷脂化的咪唑喹啉产物。
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