Tricrilactones A–H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons from Trichocladium crispatum, an Alpine Moss‐Associated Fungus. Issue 15 (6th March 2023)

• Record Type: Journal Article
• Authors: Han, Wen‐Bo; Zhai, Yi‐Jie; Zhang, Rong; Gong, Xu‐Shun; Li, Jia‐Qian; Xu, Gong; Lei, Xinxiang; Du, Liangcheng; Gao, Jin‐Ming
• Is Part Of: Angewandte Chemie international edition. Volume 62:Issue 15(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-06
• Subjects: Antiosteoporosis -- Fungal Natural Products -- Isotope Labeling -- Macrolides -- Structure Elucidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202300773
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Tricrilactones A–H (1 –8 ), a new family of oligomeric 10‐membered macrolides featuring collectively five unique ring skeletons, were isolated from a hitherto unexplored fungus, Trichocladium crispatum . Compounds 1 and 7 contain two unconventional bridged (aza)tricyclic core skeletons, 2, 3, 5, and 6 share an undescribed tetracyclic 9/5/6/6 ring system, 4 bears an uncommon 9/5/6/10/3‐fused pentacyclic architecture, and 8 is a dimer bridged by an unexpected C−C linkage. Their structures, including absolute configurations, were elucidated by spectroscopic analysis, quantum chemical calculations, and X‐ray diffraction analysis. Importantly, the absolute configuration of the highly flexible side chain of 1 was resolved by the asymmetric synthesis of its four stereoisomers. The intermediate‐trapping and isotope labeling experiments facilitated the proposal of the biosynthetic pathway for these macrolides. In addition, their antiosteoporosis effects were evaluated in vivo (zebrafish). Abstract : A family of oligomeric 10‐membered macrolides, tricrilactones A–H, was isolated from the moss‐derived fungus T. crispatum . Intermediate‐trapping and isotope labeling experiments provided evidence for their proposed biosynthetic pathway. The compounds were found to be potent antiosteoporosis agents in vivo, whereby tricrilactone G (top right‐hand structure) restored bone formation‐resorption homeostasis and promoted cartilage and skeletal development.