基于铃木耦合反应合成源自VATP酶抑制剂阿奇佐利德天然产物的片段。

Vincent Cooper T, Long Evan T, Jones Holly C, Young Jeffrey C, Spiegel P Clint, O'Neil Gregory W

Department of Chemistry, Western Washington University Bellingham WA USA 98229

Department of Biology, Western Washington University Bellingham WA USA 98229.

RSC Adv. 2019 Oct 10;9(55):32210-32218. doi: 10.1039/c9ra07050h. eCollection 2019 Oct 7.

An archazolid natural product fragment that displays dose-dependent inhibition of the vacuolar-type ATPase (VATPase) has been synthesized by a high-yielding Suzuki coupling of two complex subunits. Similarly, a further simplified fragment was prepared and evaluated for VATPase inhibitory activity. This compound did inhibit the VATPase, as evidenced by growth inhibition of etiolated seedlings, however at approximately 10× lower potency than the more complex fragment. Cyclooxygenase (COX) enzyme inhibition was not observed for either fragment.

通过两个复杂亚基的高产铃木偶联反应合成了一种显示出对液泡型ATP酶（V-ATP酶）剂量依赖性抑制作用的阿扎利德天然产物片段。同样，制备了一个进一步简化的片段并对其V-ATP酶抑制活性进行了评估。该化合物确实抑制了V-ATP酶，黄化幼苗的生长抑制证明了这一点，然而其效力比更复杂的片段低约10倍。两个片段均未观察到对环氧合酶（COX）的抑制作用。