Tricrilactones A–H, Potent Antiosteoporosis Macrolides with Distinctive Ring Skeletons from Trichocladium crispatum, an Alpine Moss‐Associated Fungus

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).