Wloch Morgan, Sun Zhaozhao, Valzer Emmanuel, Pouységu Laurent, Quideau Stéphane
Université de Bordeaux, ISM (CNRS-UMR 5255), 351 cours de la Libération, 33405 Talence Cedex, France.
Institut Universitaire de France, 1 rue Descartes, 75231 Paris Cedex 05, France.
Org Lett. 2024 Jul 26;26(29):6086-6091. doi: 10.1021/acs.orglett.4c01653. Epub 2024 Jul 11.
An enantioselective synthesis of the bacterial metabolite (+)-strepantibin A, a novel inhibitor of the hexokinase II (HK2) in cancer cells, is described. Its monomethylated resorcinolic -terphenyl core was conveniently prepared through a Danheiser benzannulation. The elaboration of its -quinolic chiral center was accomplished by relying on an iodyl-promoted regio- and enantioselective hydroxylative dearomatization. The olefinic side-chain of the resulting -quinol was finally oxygenated under Wacker-type conditions to generate the propanone appendage of (+)-strepantibin A.
本文描述了细菌代谢产物(+)-链抗生物素蛋白A的对映选择性合成，它是癌细胞中己糖激酶II（HK2）的一种新型抑制剂。其单甲基化的间苯二酚类-三联苯核心通过丹海泽苯并环化反应方便地制备而成。其喹啉类手性中心的构建是依靠碘酰促进的区域和对映选择性羟基化脱芳构化反应来完成的。所得喹啉的烯侧链最终在瓦克型条件下氧化，生成(+)-链抗生物素蛋白A的丙酮附属物。
