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

Abstract

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.