A Chiral‐Pool‐Based Approach to the Core Structure of (+)‐Hyperforin

Abstract

Asymmetric entry to the bicyclic core structure of (+)‐hyperforin is presented. The developed synthetic strategy features a carefully orchestrated stereochemical relay from the single chiral center residing within (–)‐Wieland–Miescher ketone and an intramolecular aldol reaction to cast the [3.3.1] bicyclic scaffold found in a diverse array of polycyclic polyprenylated acylphloroglucinols.

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

“…Triflation of the C-6 ketone with McMurry’s reagent (PhNTf 2 ) [83–86] followed by a Pd(0)-catalyzed carbomethoxylation [87–90] produced the desired C-ring lactone 20 in 61% yield. Epoxidation of the C-6/C-7 enone with NaOH/H 2 O 2 followed by oxidative cleavage of the C-11 terminal alkene under OsO 4 /NaIO 4 conditions [91–92] afforded the corresponding C-11 aldehyde. Exposure of this intermediate to Jones oxidation triggered a highly efficient oxidation–epoxide opening [93–98] reaction cascade [99–100] to construct the critical D-ring of 9 (46% yield, over 3 steps).…”

Enantioselective Total Synthesis of Hyperforin

“…While these PPAPs contain a geminal dimethyl group at the C8 position (hyperforin numbering), differential substitution at the hyperforin C8 position renders these otherwise effective strategies inapplicable toward hyperforin total synthesis. Numerous approaches toward hyperforin have only resulted in one total synthesis of ent -hyperforin, accomplished by the Shibasaki group in 2010 . Given the considerable length of this route (51 steps from propargyl bromide), we set out to devise a new enantioselective approach that would not only incorporate elements of modularity but also exploit latent symmetry.…”

Research Progress of Polycyclic Polyprenylated Acylphloroglucinols

“…In addition to total synthesis studies of PPAPs, other teams such as Couladouros, , Marazano, − Mehta, − Takagi, , and Chen, et al, have also made efforts to develop synthetic methodologies and strategies toward construction of the bicyclo[3.3.1]­nonane core of these complicated natural products. − This work has been summarized in other reviews and hence is not elaborated in detail here. − …”