Total Synthesis of (+)‐Erogorgiaene and the Pseudopterosin A−F Aglycone via Enantioselective Cobalt‐Catalyzed Hydrovinylation. Issue 45 (26th June 2021)

• Record Type: Journal Article
• Authors: Movahhed, Sohajl; Westphal, Julia; Kempa, Alexander; Schumacher, Christian Eric; Sperlich, Julia; Neudörfl, Jörg‐Martin; Teusch, Nicole; Hochgürtel, Matthias; Schmalz, Hans‐Günther
• Is Part Of: Chemistry. Volume 27:Issue 45(2021)
• Page Start: 11574
• Page End: 11579
• Publication Date: 2021-06-26
• Subjects: cationic cyclization -- cobalt catalysis -- diterpenes -- glycosides -- hydrovinylation -- marine natural products; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202101863
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt‐catalyzed hydrovinylation as the chirogenic step. Other noteworthy C−C bond forming transformations include diastereoselective Lewis acid‐mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4‐methyl‐styrene the anti‐tubercular agent (+)‐erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti‐inflammatory activity (inhibition of LPS‐induced NF‐κB activation) as a natural mixture of pseudopterosins A−D or iso ‐pseudopterosin A, prepared by β‐ D ‐xylosylation of the synthetic aglycone. Abstract : Applied metal catalysis : Exploiting a practical protocol for the asymmetric hydrovinylation of stryrenes in the opening move, the stereoselective total synthesis of bioactive constituents of the soft coral pseudopterogorgia elisabethae was efficiently achieved in sequence of metal‐mediated steps to provide sufficient material for further biological investigations.