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Total Synthesis of (+)‐Erogorgiaene and the Pseudopterosin A−F Aglycone via Enantioselective Cobalt‐Catalyzed Hydrovinylation
Author(s) -
Movahhed Sohajl,
Westphal Julia,
Kempa Alexander,
Schumacher Christian Eric,
Sperlich Julia,
Neudörfl JörgMartin,
Teusch Nicole,
Hochgürtel Matthias,
Schmalz HansGünther
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101863
Subject(s) - aglycone , enantioselective synthesis , yield (engineering) , chemistry , catalysis , total synthesis , stereochemistry , cobalt , combinatorial chemistry , organic chemistry , materials science , glycoside , metallurgy
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.