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

Abstract

AbstractTricrilactones 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. Compounds1and7contain two unconventional bridged (aza)tricyclic core skeletons,2,3,5, and6share an undescribed tetracyclic 9/5/6/6 ring system,4bears an uncommon 9/5/6/10/3‐fused pentacyclic architecture, and8is 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 of1was 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).