State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics , Peking University Shenzhen Graduate School , Shenzhen 518055 , China.
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and Beijing National Laboratory for Molecular Science (BNLMS), and Peking-Tsinghua Center for Life Sciences , Peking University , Beijing 100871 , China.
Org Lett. 2020 Feb 21;22(4):1644-1647. doi: 10.1021/acs.orglett.0c00241. Epub 2020 Feb 10.
The asymmetric total synthesis of (-)-guignardones A () and B () has been accomplished. The highly oxidized 6-oxabicyclo[3.2.1]octane core was constructed from d-quinic acid via substitution/desulfurization reaction with thiophenol to forge the bridged ring scaffold, and a Pummerer rearrangement and 1,4-addition/elimination sequence was employed to install the β-carbonyl group at the congested C-1 position. A late-stage Knoevenagel condensation-6π-electrocyclization and directed hydrogenation formed (-)-guignardone B (), which was subjected to dehydration to furnish (-)-guignardone A ().
(-)-guignardones A () 和 B () 的非对映全合成已经完成。通过用巯基苯酚取代/脱硫反应，从 D-奎尼酸构建了高度氧化的 6-氧杂双环[3.2.1]辛烷核心，形成了桥环支架，并采用 Pummerer 重排和 1,4-加成/消除序列在拥挤的 C-1 位置安装了β-羰基。晚期的 Knoevenagel 缩合-6π-电环化和定向氢化形成了 (-)-guignardone B ()，然后进行脱水得到 (-)-guignardone A ()。
