Researchers from Shandong University, led by Professors Li Shengying, in collaboration with Professor David H. Sherman from the University of Michigan, has published a comprehensive review article titled "The Mutually Inspiring Biological and Chemical Synthesis of Fungal Bicyclo[2.2.2]diazaoctane Indole Alkaloids" in the prestigious journal Chemical Reviews (Impact Factor: 51.4). This review highlights the latest advancements in the biosynthesis and chemical synthesis of fungal bicyclo[2.2.2]diazaoctane (BCDO) indole alkaloids, a fascinating family of natural products with diverse biological activities and structural complexity. The article also outlines future opportunities and challenges in this field.

For over half a century, fungal indole alkaloids featuring the unique BCDO core structure have captivated the scientific community. The globally used antiparasitic drug Derquantel is derived from the BCDO indole alkaloid Paraherquamide A. These compounds exhibit a wide range of biological activities, including anthelmintic, insecticidal, antitumor, antiviral, and antibacterial activities. Additionally, they display remarkable structural diversity, with specific fungal strains producing distinct diastereomers and enantiomers. The intriguing biological activities, unique chemical structures, and mysterious biosynthetic pathways of BCDO indole alkaloids have attracted extensive research in natural product chemistry, biochemistry, synthetic chemistry, and medicinal chemistry.

This review provides a comprehensive overview of the research journey since the discovery of the first BCDO family member, Brevianamide A, in 1969. It systematically summarizes key breakthroughs in the field, including the biosynthesis of the BCDO core structure, the diverse structural variations of diastereomers and enantiomers, and other unique substructures. The article emphasizes the mutual inspiration and collaboration between biologists and synthetic chemists, which has significantly advanced the exploration of BCDO indole alkaloid synthesis. Furthermore, the review offers perspectives on future research directions and provides new insights into unresolved biosynthetic mysteries, paving the way for further discoveries in this field.

The authors dedicate this review to the late Professor Robert M. Williams (1953–2020), a pioneer and leader in the chemical synthesis of BCDO indole alkaloids. Professor Williams made groundbreaking contributions to the biomimetic synthesis of these natural products, and this article is a tribute to his remarkable legacy. This work was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Shandong Provincial Natural Science Foundation, the Taishan Young Scholars Program, the Overseas Excellent Young Scientists Fund Program of Shandong Province, the Natural Science Foundation of Jiangsu Province, and NIH grant R35 GM118101, as well as the Hans W. Vahlteich Professorship.