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Total Synthesis of the Polyoxygenated Sesquiterpenes Guignarderemophilanes C and D
Author(s) -
Ilazi Agron,
Liffert Raphael,
Gademann Karl
Publication year - 2018
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201800011
Subject(s) - chemistry , total synthesis , regioselectivity , mitsunobu reaction , epoxide , carvone , stereochemistry , aldol condensation , bicyclic molecule , derivatization , natural product , ring (chemistry) , combinatorial chemistry , aldol reaction , steric effects , organic chemistry , catalysis , high performance liquid chromatography , chromatography , essential oil , limonene
The total syntheses of the neural anti‐inflammatory agents guignarderemophilanes C and D have been accomplished for the first time starting from γ ‐hydroxy carvone in 15 and 14 steps, respectively. The presented synthetic route proceeds via a known intermediate, whose synthesis has been elaborated in our group in the course of the total synthesis of the sesquiterpenoid periconianone A. Key for the successful conversion of this intermediate into both targets was finding a suitable strategy to install the 1,2,3‐trihydroxylated A‐ring scaffold. For this purpose, we effectively employed a Mitsunobu inversion, epoxidation, and regioselective epoxide opening sequence, before the bicyclic ring system was constructed by an aldol condensation reaction on a sterically demanding substrate. Our reported synthesis set the stage for SAR studies to prepare even more potent compounds by modification and derivatization of the natural product's scaffold.