Biomimetic total synthesis of plakortone Q via acid-mediated tandem cyclization

Abstract

Plakortone Q and plakdiepoxide are natural polyketides isolated from the marine sponge Plakortis simplex. Bicyclo[3.3.0]furanolactone compounds, including plakortone Q, are expected to exhibit a wide range of pharmacological activities. Therefore,...

Total Synthesis of Marine Polyketide Plakortone Q

“…Epoxyketone 8 (dr 6 : 1) was prepared via Sharpless asymmetric epoxidation in a manner similar to that used for the synthesis of 1 in our previous report. 11) It was then con-verted to a C 3 -homologated silylether using the Wittig reaction by treatment with phosphonium ylide generated from (3-((tert-butyldimethylsilyl) oxy) propyl) triphenylphosphonium bromide. 12) Subsequent desilylation afforded (E)-homoallylic alcohol 9 (dr 6 : 1) in 77% yield and (Z)-homoallylic alcohol 10 (dr 6 : 1) in 14% yield.…”

“…10) In our 2022 study of the biomimetic total synthesis of plakortone Q (1), we synthesized both 8S and 8R stereoisomers and determined their absolute configurations as 3S, 4S, 5S, 6S, and 8S. 11) In our previous study, 11) we found structural homology between plakdiepoxide (2), an unprecedented acyclic polyketide containing a vicinal syn-diepoxide moiety on the acyclic chain isolated from P. simplex, and plakortone Q (1). Therefore, we hypothesized that these two natural products would be biosynthesized via the same precursor.…”

Marine natural products

“…[426][427][428][429][430] Numerous rst total syntheses of sponge metabolites were published in 2022. These include the syntheses of ethyl branched polyketides plakortone Q and plakdiepoxide, 431 and peptides stylissatin B, 432 cyclotheonellazole A, 433 and stylopeptide II, the last of which was prepared synthetically on the gram scale. 434 Hemicalide is an extremely potent (sub nM IC 50 ) cytotoxin, although only the planar structure was originally published within a patent application.…”

Total Synthesis and Structural Revision of Cephalosporolide J

“…In recent years, these polyketides have attracted a great deal of attention from many research groups active in synthetic chemistry, due to their interesting molecular architectures and pharmacological profiles. 6 Notably, our research group too has been conducting synthetic studies on these polyketides, and we recently realized the total syntheses of plakortone Q 7 and ascospiroketal B. 8…”

“…5 In recent years, these polyketides have attracted a great deal of attention from many research groups active in synthetic chemistry, due to their interesting molecular architectures and pharmacological profiles. 6 Notably, our research group too has been conducting synthetic studies on these polyketides, and we recently realized the total syntheses of plakortone Q 7 and ascospiroketal B. 8 In 2018, Yang and colleagues discovered the novel spirocyclic compound cephalosporolide J (1) during a bioassay-guided investigation of the deep sea sediment-derived fungus Penicillium commune.…”