Construction of Fused–Bridged Tricycles by Molecular Reorganization Involving Prins Cyclization/Dicycloexpansion
Abstract
Abstract The development of efficient methods for constructing structurally complex and diverse polycyclic carbon frameworks remains in high demand for the synthesis of pharmaceuticals and bioactive natural products. One such method lies in engineered one‐step molecular reorganization through the cascade cyclization/cycloexpansion of rationally designed precursors with interconnected small‐ring systems. Here, we have strategically designed and developed a synthetically valuable method to construct fused‐bridged tricyclic systems through cascade Prins cyclization/dicycloexpansion of substrates with a cycloalkylidene (CAD) tethered to a cycloketones. This methodology features high step economy, reaction efficiency, and selectivity, as well as a broad substrate tolerance. Diversification through variation of the size of the small ring, the linker length, and the linking site has enabled the efficient synthesis of six types of fused‐bridged tricyclic scaffolds, which are found frequently in bioactive natural products. Based on supporting experiments and DFT calculations, a plausible reaction mechanism is also proposed.
Article Details
Authors (13)
Yun‐Peng Wang
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Zi‐Lin Gao
School of Chemistry and Chemical Engineering School of Pharmaceutical Sciences Frontiers Science Center for Transformative Molecules State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai 200240 China
Kun Fang
Yong‐Qiang Tu
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Si‐Hua Hou
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Hong Wang
Ka Lu
School of Pharmaceutical Sciences, School of Chemistry and Chemical Engineering, School of Artificial Intelligence, Frontier Scientific Center of Transformative Molecules, National Key Laboratory of Innovative Immunotherapy, MoE Key Laboratory of Artificial Intelligence
Bao‐Heng Dou
School of Chemistry and Chemical Engineering School of Pharmaceutical Sciences Frontiers Science Center for Transformative Molecules State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai 200240 China
Jun Xue
Tian Ke
Chemical Sciences Division
Shu‐Yu Zhang
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China
Zhi‐Min Chen
State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China
Tong‐Mei Ding
School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China