Gonzalez Elijah C, de la Torre Roehl Isabel M, Stoltz Brian M
Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology Pasadena CA 91125 USA
Chem Sci. 2025 Jun 4;16(25):11381-11385. doi: 10.1039/d5sc02952j. eCollection 2025 Jun 25.
We report a non-biomimetic total synthesis of (+)-daphnepapytone A, an unprecedented member of the guaiane-derived sesquiterpenoids that displays moderate inhibitory activity against α-glycosidase (IC = 159 ± 2.1 μM) and possesses a highly strained bridging cyclobutane motif. Our approach provided expedient access to the tetracyclic core of (+)-daphnepapytone A through an intramolecular allenyl thermal [2 + 2] cycloaddition and a Pauson-Khand reaction with a labile cyclobutane. Finally, a late-stage oxidation/reduction sequence delivered (+)-daphnepapytone A with striking chemoselectivity and excellent diastereoselectivity.
我们报道了(+)-瑞香番荔枝酮A的非仿生全合成，它是愈创木烷衍生的倍半萜类化合物中的一个前所未有的成员，对α-糖苷酶显示出中等抑制活性（IC = 159 ± 2.1 μM），并具有高度张力的桥连环丁烷基序。我们的方法通过分子内烯丙基热[2 + 2]环加成反应和与不稳定环丁烷的Pauson-Khand反应，便捷地构建了(+)-瑞香番荔枝酮A的四环核心。最后，通过后期氧化/还原序列，以显著的化学选择性和优异的非对映选择性得到了(+)-瑞香番荔枝酮A。
