Three-Component Coupling via the Squarate Ester Cascade as a Concise Route to the Bioactive Triquinane Sesquiterpene Hypnophilin

Abstract

[reaction: see text] A squarate ester cascade is used to provide in one step, via the coupling of three reactants, a highly oxygenated linear triquinane product. The latter is transformed in nine steps into hypnophilin. The access route involves a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence.

Linear Triquinane Sesquiterpenoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis

“…In 2002, Geng and co-workers presented a direct 10-step route from a squarate ester to hypnophilin ( 8 ) [ 70 ]. The access route involved a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence ( Scheme 20 ).…”

Asymmetric electrocyclic reactions

“…192 They subsequently found that remote stereoinduction could be achieved through the use of multiple chelating heteroatoms; 193 This methodology has also been utilized in the synthesis of several natural products including hypnophilin, coriolin, and ceratopicanol. 194,195…”

Natural sesquiterpenoids

“…194 The sesquiterpenes hypnophilin, coriolin and ceratopicanol have been synthesised as their racemates. 195,196 Another synthesis of (±)-ceratopicanol has been described by Japanese authors. 197 The total synthesis of the putative structure of isocapnellenone has been reported.…”