Total Synthesis of Linear Coumarniolignoids (+) and (-)-Sapiumin C, (-)-Moluccanin, and (-)-Hemidesminine.

Coumarinolignoids (CLs) are a class of natural products isolated from a diverse range of plant species. Due to their unique structural scaffold, they exhibit a wide range of interesting biological activities including hepatoprotective, antitumor, anti-inflammatory, and antioxidant activities among others. In this research, key intermediate 10 was used to stereoselectively synthesize CLs (7' S ,8' S )- and (7' R ,8' R )-sapiumin C 1 and 2 , (7' S ,8' S )-moluccanin 3 , and (7' S ,8' S ) hemidesminine 4 for the first time, establishing a versatile synthetic method for the stereoselective synthesis of linear CLs. The developed method includes a Mitsunobu coupling, a modified Miyaura arylation via a rhodium catalyst, and an acid-catalyzed cyclization in key bond-forming steps. The developed synthetic route allows the synthesis of both enantiomers of a given natural product from the same chiral pool reagent ( S )-solketal while allowing easy variation of aromatic substitution and hydroxymethyl/allylhydroxymethyl moieties that are common in this class of natural products.