Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St W, Hamilton, ON, Canada.
Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, 1280 Main St W, Hamilton, ON, Canada.
Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13259-13262. doi: 10.1002/anie.201606657.
The fungal secondary metabolite aspergillomarasmine A (AMA) has recently been identified as an inhibitor of metallo-β-lactamases NDM-1 and VIM-2. Described herein is an efficient and practical route to AMA and its related compounds by a sulfamidate approach. In addition, a series of derivatives has been prepared and tested for biological activity in an effort to explore preliminary structure activity relationships. While it was determined that natural LLL isomer of AMA remains the most effective inactivator of NDM-1 enzyme activity both in vitro and in cells, the structure is highly tolerant of the changes in the stereochemistry at positions 3, 6, and 9.
真菌次级代谢产物aspergillomarasmine A（AMA）最近被鉴定为金属-β-内酰胺酶 NDM-1 和 VIM-2 的抑制剂。本文描述了一种通过磺酰胺方法高效实用的 AMA 及其相关化合物的合成路线。此外，还制备了一系列衍生物，并对其生物活性进行了测试，以期探索初步的构效关系。虽然确定天然 LLL 异构体的 AMA 仍然是体外和细胞内最有效的 NDM-1 酶活性抑制剂，但该结构对 3、6 和 9 位立体化学变化具有高度耐受性。
