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

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).