Stone Steven D, Lajkiewicz Neil J, Whitesell Luke, Hilmy Ahmed, Porco John A
Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University , Boston, Massachusetts 02215, United States.
J Am Chem Soc. 2015 Jan 14;137(1):525-30. doi: 10.1021/ja511728b. Epub 2014 Dec 29.
We have previously reported asymmetric syntheses and absolute configuration assignments of the aglains (+)-ponapensin and (+)-elliptifoline and proposed a biosynthetic kinetic resolution process to produce enantiomeric rocaglamides and aglains. Herein, we report a biomimetic approach for the synthesis of enantiomerically enriched aglains and rocaglamides via kinetic resolution of a bridged ketone utilizing enantioselective transfer hydrogenation. The methodology has been employed to synthesize and confirm the absolute stereochemistries of the pyrimidone rocaglamides (+)-aglaiastatin and (-)-aglaroxin C. Additionally, the enantiomers and racemate of each metabolite were assayed for inhibition of the heat-shock response, cytotoxicity, and translation inhibition.
我们之前报道了阿格莱因（+）-波纳彭辛和（+）-椭圆叶林的不对称合成及绝对构型归属，并提出了一种生物合成动力学拆分过程来制备对映体罗卡酰胺和阿格莱因。在此，我们报道了一种仿生方法，通过利用对映选择性转移氢化对桥连酮进行动力学拆分，来合成对映体富集的阿格莱因和罗卡酰胺。该方法已用于合成并确认嘧啶酮罗卡酰胺（+）-阿格拉他汀和（-）-阿格拉罗辛C的绝对立体化学。此外，还测定了每种代谢物的对映体和外消旋体对热休克反应的抑制作用、细胞毒性和翻译抑制作用。
