Biomimetic Total Syntheses of (+)-Chloropupukeananin, (−)-Chloropupukeanolide D, and Chloropestolides

Abstract

Chloropupukeananin, chloropupukeanolides, and chloropestolides are a family of structurally complex bioactive natural products that possess highly functionalized tricyclo­[4.3.1.03,7]­decane or bicyclo[2.2.2]­octane skeletons. Biosynthesis of the chloropupukeananin family is triggered by the intermolecular heterodimeric Diels–Alder reaction between maldoxin and iso-A82775C; however, the enzymes involved have not yet been identified. We herein report the one-pot biomimetic synthesis of chloropupukeananin and chloropupukeanolide D. Moreover, the effect of the solvent on the intermolecular Diels–Alder reaction of siccayne and maldoxin suggested that the biosynthesis of the chloropupukeananin family involves a Diels–Alderase-catalyzed heterodimeric Diels–Alder reaction.

Natural epoxyquinoids: isolation, biological activity and synthesis. An update

“…131 Suzuki with colleagues developed the biomimetic total synthesis of (+)-chloropupukeananin and (−)-chloropupukeanolide D using a one-pot Diels–Alder/carbonyl–ene cascade reaction. 132 Iso-A82775C and maldoxin were chosen as starting compounds and synthesized using modified previously reported syntheses (Scheme 22).…”

“…131 Suzuki with colleagues developed the biomimetic total synthesis of (+)-chloropupukeananin and (−)-chloropupukeanolide D using a one-pot Diels-Alder/carbonyl-ene cascade reaction. 132 Iso-A82775C and maldoxin were chosen as starting compounds and synthesized using modified previously reported syntheses (Scheme 22). The reaction of iso-A82775C and maldoxin was accompanied by the formation of a mixture of products (Chloropestolide D -17% and Chloropestolide C -5%), while chloropupukeanolide D was a major product (Scheme 23).…”

Recent advances in total synthesis of natural products by masked ortho‐benzoquinones

“…Finally, the first asymmetric synthesis of chloropupukeananin ( 39 ) was achieved by migration of the p ‐orsellinate group under basic condition. [ 16 ]…”

“…Finally, the first asymmetric synthesis of chloropupukeananin (39) was achieved by migration of the p-orsellinate group under basic condition. [16] Liao and Hsu applied carbohydrate-templated asymmetric Diels-Alder reaction of MOB [17] in the asymmetric total synthesis of ent-penicillones A (40) and B (41) (Scheme 10) and revised the absolute configuration of related Diels-Alder adducts. [18] At first, β-glycosylated phenol 65 was synthesized from 3,5-dimethylcatechol 64 and D-glucopyranose derivative by glycosylation.…”

Total Syntheses of Chloropupukeananin and Its Related Natural Products

“…As shown in Snyder's synthesis, the nonselectivity of the chlorination of these compounds is a fundamental issue that may necessitate alternative functionalization reactions. The alternative synthesis [38] was initiated with commercial 2-chloro-1,4-dimethoxybenzene, which was converted to methyl 4-chloro-2,5-dimethoxybenzoate 42 by three-step sequence (formylation, Pinnick oxidation, and acidic esterification). The oxidative nucleophilic substitution reaction [39,40] using PIDA in trifluoroacetic acid (TFA)/AcOH mixed solvent occurred selectively at the C3 position (C3/C6 = 6:1) to give 43, which was directly subjected to basic hydrolysis to produce phenol 39 in 68% yield.…”