Phospholipidation of TLR7/8-active imidazoquinolines using a tandem phosphoramidite method

TETRAHEDRON LETTERS

卷:57

Article

Bazin, Helene G.^1,2  Bess, Laura S.^1,2  Livesay, Mark T.^1,2  Mwakwari, Sandra C.^1,3  Johnson, David A.¹ 

[1] GSK Vaccines, 553 Old Corvallis Rd, Hamilton, MT 59840 USA

[2] Univ Montana, 1121 E Broadway,Suite 128, Missoula, MT 59802 USA

[3] Tetra Discovery Partners, 4717 Campus Dr, Kalamazoo, MI 49008 USA

关键词: TLR7/8;    Phospholipidation;    Imidazoquinoline;    Phosphoramidite;   

DOI  :  10.1016/j.tetlet.2016.03.091

来源: Elsevier

【 摘 要 】

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-sn-glycerol or 3-chlolesterylalkanol with 2-cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite in the presence of 1H-tetrazole followed by treatment of the resulting N,N'-diisopropylphosphoramidite lipid in situ with 1-imidazoquinolinylalkanols. The resulting phosphite can be purified or directly oxidized with t-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. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

Free