Lu Yimin, Nagashima Tadamichi, Miriyala Bruhaspathy, Conde Joanne, Zhang Wei
Fluorous Technologies, Inc., Pittsburgh, Pennsylvania 15238, USA.
J Comb Chem. 2010 Jan-Feb;12(1):125-8. doi: 10.1021/cc9001636.
A fluorous linker-assisted synthetic protocol has been developed for preparation of sclerotigenin-type benzodiazepine-quinazolinone library containing 144 analogues. Amide coupling of fluorous trimethoxybenzyl (TMB)-protected amino esters with anthranilic acids followed by base-promoted cyclizations afforded 4-benzodiazepine-2,5-diones. Further derivatization of benzodiazepinediones by reacting with azidobenzoyl chlorides, cyclization, and fluorous linker cleavage afforded the desired compound library. The reaction intermediates were purified by fluorous solid-phase extraction (F-SPE) and final products were further purified by prep-HPLC.
已开发出一种含氟连接子辅助的合成方案，用于制备包含144种类似物的硬皮菌素型苯并二氮杂䓬-喹唑啉酮文库。用含氟三甲氧基苄基（TMB）保护的氨基酸酯与邻氨基苯甲酸进行酰胺偶联，随后进行碱促进的环化反应，得到4-苯并二氮杂䓬-2,5-二酮。苯并二氮杂䓬二酮与叠氮苯甲酰氯反应、环化以及含氟连接子裂解，进一步衍生化得到所需的化合物文库。反应中间体通过含氟固相萃取（F-SPE）进行纯化，最终产物通过制备型高效液相色谱（prep-HPLC）进一步纯化。
