Total Synthesis of abeo-Steroids via Cycloaddition Strategy

作者：Long Min, Liping Zhong, Chuang‐Chuang Li · 发表于：Accounts of Chemical Research · 年份：2023 · DOI：10.1021/acs.accounts.3c00350 · 被引用次数：29 · 研究领域：Bioactive Compounds and Antitumor Agents、Marine Sponges and Natural Products、Organic Chemistry Cycloaddition Reactions

Conspectus Steroids continue to play a significant role in organic chemistry, medicinal chemistry, and drug discovery due to their important biological activities and diverse intriguing structures. Although synthetic organic chemists have successfully constructed and elaborated the classical [6–6–6–5] tetracyclic steroid skeleton for nearly a century, synthesis of the unusual rearranged steroids, particularly abeo -steroids with a medium-sized ring, remains a challenge in the synthetic community. Furthermore, the structures of abeo -steroids are complex and diverse, containing a seven-membered ring embedded in the fused or bridged A/B ring system and possessing numerous stereogenic centers. Besides their structural complexity, various abeo -steroids have shown remarkable biological activities. However, the relative scarcity of abeo -steroids in natural sources has impeded the systematic evaluation of their biological activities. In addition, direct strategies to build the core structures of abeo -steroids are very rare, partially because of the high ring-strain energies of their rearranged A/B ring systems. Therefore, the development of direct and efficient synthetic approaches to these complex molecules is highly desired. Our long-standing interest in the total synthesis of abeo -steroids and the development of new cycloaddition reactions for streamlining complex molecule synthesis have led us to develop a series of unique and powerful intramolecular cycloaddition strategies...