Enantioselective total synthesis of hyperforin.

A modular, 18-step total synthesis of hyperforin is described. The natural product was quickly accessed using latent symmetry elements, whereby a group-selective, Lewis acid-catalyzed epoxide-opening cascade cyclization was used to furnish the bicyclo[3.3.1]nonane core and set two key quaternary stereocenters.

• Publication year

  2013

• Venue

  Journal of the American Chemical Society

• Publication date

  2013-01-16

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/ja312150dPMID 23270309
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Stereoselective total synthesis of nemorosone.

  2012cited by this paper
• A Chiral‐Pool‐Based Approach to the Core Structure of (+)‐Hyperforin

  2012cited by this paper
• The chemistry of the polycyclic polyprenylated acylphloroglucinols.

  2012cited by this paper
• Asymmetric total synthesis of (+)- and (-)-clusianone and (+)- and (-)-clusianone methyl enol ether via ACC alkylation and evaluation of their anti-HIV activity.

  2011cited by this paper
• Synthetic Efforts Toward [3.3.1] Bridged Bicyclic Phloroglucinol Natural Products.

  2011cited by this paper
• The total synthesis of hyperpapuanone, hyperibone L, epi-clusianone and oblongifolin A.

  2011cited by this paper
• An unexpected oxidation of unactivated methylene C-H using DIB/TBHP protocol.

  2011cited by this paper
• An unprecedented method for the generation of tert-butylperoxy radical using DIB/TBHP protocol: solvent effect and application on allylic oxidation.

  2010cited by this paper
• Catalytic enantioselective alkylative dearomatization-annulation: total synthesis and absolute configuration assignment of hyperibone K.

  2010cited by this paper
• Total synthesis of plukenetione A.

  2010cited by this paper
• Phloroglucinol compounds of natural origin: synthetic aspects.

  2010cited by this paper
• Development of a strategy for the asymmetric synthesis of polycyclic polyprenylated acylphloroglucinols via N-amino cyclic carbamate hydrazones: application to the total synthesis of (+)-clusianone.

  2010cited by this paper
• Catalytic enantioselective claisen rearrangements of O-allyl β-ketoesters.

  2010cited by this paper
• Expedient synthesis of ialibinones A and B by manganese(III)-mediated oxidative free radical cyclisation

  2010cited by this paper
• Synthetic studies toward the PPAP natural products, prolifenones A and B and hyperforin: an Effenberger cyclization approach

  2010cited by this paper
• Catalytic asymmetric total synthesis of ent-hyperforin.

  2010cited by this paper
• Total syntheses of polycyclic polyp renylated acylphloroglucinols

  2010cited by this paper
• Synthesis of Nemorosone viaa Difficult Bridgehead Substitution Reaction

  2010cited by this paper
• The first catalytic asymmetric total synthesis of ent-hyperforin

  2010cited by this paper
• A short biomimetic approach to the fully functionalized bicyclic framework of type A acylphloroglucinols.

  2009cited by this paper
• St. John’s Wort – an Overview

  2009cited by this paper
• Construction of the adamantane core of plukenetione-type polycyclic polyprenylated acylphloroglucinols.

  2008cited by this paper
• Rapid and enantioselective synthetic approaches to germanicol and other pentacyclic triterpenes.

  2008cited by this paper
• Photochemical degradation of hyperforin

  2008cited by this paper
• Biosynthesis of hyperforin and adhyperforin from amino acid precursors in shoot cultures of Hypericum perforatum.

  2007cited by this paper
• Synthetic studies towards garsubellin A: synthesis of model systems and potential mimics by regioselective lithiation of bicyclo[3.3.1]nonane-2,4,9-trione derivatives from catechinic acid.

  2007cited by this paper
• Alpha,alpha'-annulation of 2,6-prenyl-substituted cyclohexanone derivatives with malonyl chloride: application to a short synthesis of (+/-)-clusianone. Formation and rearrangement of a biogenetic-like intermediate.

  2007cited by this paper
• Differentiation of nonconventional "carbanions"-the total synthesis of nemorosone and clusianone.

  2007cited by this paper
• Kinetic resolution in a bridgehead lithiation mediated by a chiral bis-lithium amide: assignment of the absolute configuration of clusianone.

  2007cited by this paper
• Rapid access to polyprenylated phloroglucinols via alkylative dearomatization-annulation: total synthesis of (+/-)-clusianone(1).

  2007cited by this paper
• Synthesis of polyprenylated acylphloroglucinols using bridgehead lithiation: the total synthesis of racemic clusianone and a formal synthesis of racemic garsubellin A.

  2007cited by this paper
• Hyperforin, a new lead compound against the progression of cancer and leukemia?

  2006cited by this paper
• Hyperforin.

  2006cited by this paper
• Synthesis of (+/-)-clusianone: high-yielding bridgehead and diketone substitutions by regioselective lithiation of enol ether derivatives of bicyclo[3.3.1]nonane-2,4,9-triones.

  2006cited by this paper
• Polycyclic polyprenylated acylphloroglucinols.

  2006cited by this paper
• Total synthesis of (+/-)-garsubellin A.

  2006cited by this paper
• Hyperforin: more than an antidepressant bioactive compound?

  2006cited by this paper
• Total synthesis of garsubellin A.

  2005cited by this paper
• Total Synthesis of (±)-Garsubellin A

  2005cited by this paper
• Construction of highly functionalized medium-sized rings: synthesis of hyperforin and perforatumone model systems.

  2005cited by this paper
• Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures.

  2005cited by this paper
• The first prenylation step in hyperforin biosynthesis.

  2005cited by this paper
• Aristoforin, a Novel Stable Derivative of Hyperforin, Is a Potent Anticancer Agent

  2005cited by this paper
• Challenge toward structural complexity using asymmetric catalysis: target-oriented development of catalytic enantioselective Diels-Alder reaction.

  2004cited by this paper
• Instability of St. John's wort (Hypericum perforatum L.) and degradation of hyperforin in aqueous solutions and functional beverage.

  2004cited by this paper
• Oxidative fragmentation of the bridged beta-triketone core of hyperforin

  2004cited by this paper
• Current St John's wort research from mode of action to clinical efficacy.

  2003cited by this paper
• 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin.

  2003cited by this paper
• Synthesis of the core bicyclic system of hyperforin and nemorosone

  2003cited by this paper
• Structural investigations of isomeric oxidised forms of hyperforin by HPLC-NMR and HPLC-MSn.

  2003cited by this paper
• Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety.

  2002cited by this paper
• Biosynthesis of hyperforin in Hypericum perforatum.

  2002cited by this paper
• St John's wort: Prozac from the plant kingdom.

  2001cited by this paper
• St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature

  2001cited by this paper
• St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.

  2000cited by this paper
• Efficient and Recyclable Monomeric and Dendritic Ru-Based Metathesis Catalysts

  2000cited by this paper
• Oxidation products of hyperforin from Hypericum perforatum.

  1998cited by this paper
• Hyperforin as a possible antidepressant component of hypericum extracts.

  1998cited by this paper
• STEREOSPECIFIC SYNTHESIS OF TETRASUBSTITUTED Z-ENOL SILYL ETHERS BY A THREE COMPONENT COUPLING PROCESS

  1997cited by this paper
• Allylbarium Reagents: Unprecedented Regio- and Stereoselective Allylation Reactions of Carbonyl Compounds

  1994cited by this paper
• Highly γ-Selective Coupling of Siloxyallylbarium Reagent with Carbonyl Compounds and Alkyl Halides

  1993cited by this paper
• Improved methods for the radical deoxygenation of secondary alcohols

  1989cited by this paper
• Free radical cyclisation of unsaturated epoxides

  1989cited by this paper
• 2-thienyl(cyano)copper lithium. A lower order, stable “cuprate in a bottle” precursor to higher order reagents

  1987cited by this paper
• Procedure for the catalytic asymmetric epoxidation of allylic alcohols in the presence of molecular sieves

  1986cited by this paper
• One electron C-C bond forming reactions via allylstannanes: scope and limitations

  1985cited by this paper
• A new one-electron carbon-carbon bond-forming reaction: separation of the chain-propagation steps in free-radical allylation

  1985cited by this paper
• Dimethylboron bromide and diphenylboron bromide: cleavage of acetals and ketals

  1984cited by this paper
• The Absolute Configuration of Hyperforin, an Antibiotic from Hypericum perforatum L., Based on the Crystal Structure Determination of its p-Bromobenzoate Ester.

  1983cited by this paper
• Cleavage of carbonoxygen bonds. Dimethylboron bromide. A new reagent for ether cleavage

  1983cited by this paper
• RULES FOR RING CLOSURE: APPLICATION TO INTRAMOLECULAR ALDOL CONDENSATIONS IN POLYKETONIC SUBSTRATES

  1982cited by this paper
• The relative stereochemistry of hyperforin - an antibiotic from L.

  1982cited by this paper
• Alkylation of 1,5-dimethoxy-1,4-cyclohexadiene. A convenient synthesis of 2-alkyl- and 2-alkenyl-1,3-cyclohexanediones

  1977cited by this paper
• The structure of hyperforin

  1975cited by this paper
• [Antibiotic hyperforin from Hypericum perforatum L].

  1971cited by this paper
• The FASEB Journal • Research Communication Hyperforin—a key constituent of St. John’s wort specifically activates TRPC6 channels

  year unknowncited by this paper

• Total Synthesis of (+)-Melicolone K Enabled by a Late-Stage Programmed C-H Functionalization.

  2026cites this paper
• Concise Syntheses of Harziane Diterpenoids by Merging Local Desymmetrization and Radical Retrosynthesis.

  2025cites this paper
• Hyperimonates A and B, a pair of unprecedented polyprenylated acylphloroglucinols from Hypericum monogynum: Structural elucidation, total synthesis, and lipid-lowering activity

  2025cites this paper
• Enantioselective Total Synthesis of (-)-Bisabosqual F via N-Heterocyclic Carbene Catalyzed (4+2) Annulation.

  2025cites this paper
• Transannular Acylation Facilitates C5–C9 Bond Formation in Hyperforin Total Synthesis

  2025cites this paper
• Total Synthesis of Hypersampsone M

  2024cites this paper
• Neurotrophic Natural Products.

  2024cites this paper
• Hyperatins A-D, highly oxidized polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum L. with hypoglycemic potential in liver cells.

  2024cites this paper
• The Total Synthesis of Hyperfirin via a Cyclooctadiene Strategy.

  2024cites this paper
• Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond.

  2024cites this paper
• Asymmetric Total Synthesis of (+)-Hyperbeanol A.

  2024cites this paper
• Catalytic prenyl conjugate additions for synthesis of enantiomerically enriched PPAPs

  2024cites this paper
• Sequential Dieckmann cyclization enables the total synthesis of 7-epi-clusianone and 18-hydroxy-7-epi-clusianone.

  2023cites this paper
• Total synthesis and structural reassignment of garcinielliptone FC, a polycyclic polyprenylated acylphloroglucinol with diverse bioactivity.

  2023cites this paper
• Enantioselective Synthesis of (-)-C10-Hydroxyacutuminine.

  2022cites this paper
• Dearomative logic in natural product total synthesis.

  2022cites this paper
• Evolution of a Synthetic Strategy for Garsubellin A.

  2022cites this paper
• Recent advances in the synthesis of natural products containing the phloroglucinol motif.

  2022cites this paper
• Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron.

  2022cites this paper
• Total Synthesis of a PPAP, Nemorosonol, Using a Tandem Michael Addition-Intramolecular Aldol Reaction.

  2022cites this paper
• Synthesis of 3-epi-Hypatulin B Featuring a Late-Stage Photo-Oxidation in Flow.

  2022cites this paper
• Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin.

  2022cites this paper
• Enantioselective Total Synthesis of (+)‐Garsubellin A

  2021cites this paper
• Strategies towards endo-type B polycyclic polyprenylated acylphloroglucinols: total synthesis of regio-hyperibone L and (+)-epi-clusianone

  2021cites this paper
• Organic synthesis with the most abundant transition metal-iron: from rust to multitasking catalysts.

  2021cites this paper
• Stereodivergent Strategy in Structural Determination: Asymmetric Total Synthesis of Garcinol, Cambogin, and Related Analogues.

  2021cites this paper
• Annulative Methods in the Synthesis of Complex Meroterpene Natural Products.

  2021cites this paper
• Pd-Catalyzed Enantioselective Dearomative Allylic Annulation to Access PPAPs Analogues.

  2021cites this paper
• Unprecedented polycyclic polyprenylated acylphloroglucinols with anti-Alzheimer's activity from St. John's wort

  2021cites this paper
• Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute configurations assignment of previously reported analogues.

  2021cites this paper
• Hyperacmosins H-J, three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum acmosepalum

  2020cites this paper
• Total Synthesis of (-)-Batrachotoxinin A: A Local-Desymmetrization Approach.

  2020cites this paper
• Asymmetric Total Synthesis of (-)-Guignardones A and B.

  2020cites this paper
• Programmable meroterpene synthesis

  2020cites this paper
• Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

  2020cites this paper
• Total Synthesis and Anticancer Activity of (+)-Hypercalin C and Congeners.

  2019cites this paper
• The Total Synthesis of Chalcitrin.

  2019cites this paper
• Hyperforin

  2019cites this paper
• Chemistry of the Secondary Metabolites of Termites.

  2019cites this paper
• Me2AlSEt-Promoted Domino Dieckmann Cyclization Enables the Total Synthesis of Polycyclic Polyprenylated Acylphloroglucinols.

  2019cites this paper
• homo-Adamantane type polycyclic polyprenylated acylphloroglucinols from Hypericum hookerianum.

  2019cites this paper
• Functional characterization of prenyltransferases involved in the biosynthesis of Polycyclic Polyprenylated Acylphloroglucinols in the genus Hypericum

  2018cites this paper
• Hypermonins A and B, two 6-norpolyprenylated acylphloroglucinols with unprecedented skeletons from Hypericum monogynum.

  2018cites this paper
• Modular Total Syntheses of Hyperforin, Papuaforins A, B, and C via Gold(I)-Catalyzed Carbocyclization.

  2018cites this paper
• Research Progress of Polycyclic Polyprenylated Acylphloroglucinols.

  2018cites this paper
• Divergent Strategy in Natural Product Total Synthesis.

  2018cites this paper
• Synthesis and Applications of Tricarbonylmethane Compounds

  2018cites this paper
• Total Synthesis of Norsampsones A and B, Garcinielliptones N and O, and Hyperscabrin A.

  2018cites this paper
• Biosynthetic and Total Synthetic Approaches for (+)-Hyperforin

  2018cites this paper
• Methylated Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum ascyron.

  2018cites this paper
• Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum.

  2018cites this paper
• Enantioselective Total Synthesis of Nigelladine A via Late-Stage C-H Oxidation Enabled by an Engineered P450 Enzyme.

  2017cites this paper
• Local Desymmetrization through Diastereotopic Group Selection: An Enabling Strategy for Natural Product Synthesis.

  2017cites this paper
• Biotechnological production of hyperforin for pharmaceutical formulation

  2017cites this paper
• Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum perforatum.

  2017cites this paper
• Computed Regioselectivity and Conjectured Biological Activity of Ene Reactions of Singlet Oxygen with the Natural Product Hyperforin

  2017cites this paper
• Super Antibiotics, Part IV. Hyperforin, Relative and Absolute Stereochemistry Elucidated by Gas-Chromatography Mass-Spectrometry with Supersonic Molecular Beams

  2017cites this paper
• seco-Polycyclic polyprenylated acylphloroglucinols with unusual carbon skeletons from Hypericum ascyron

  2017cites this paper
• TOWARDS THE TOTAL SYNTHESIS OF 7- EPI -CLUSIANONE

  2017cites this paper
• Recent applications of the 1,2-carbon atom migration strategy in complex natural product total synthesis.

  2017cites this paper
• Total Synthesis of (±)-Berkeleyone A.

  2017cites this paper
• Stereoselective construction of all-carbon quaternary stereocenters by allylboration of chiral aldehydes: synthesis of a fragment of (+)-vibsanin A

  2016cites this paper
• Polyprenylated acylphloroglucinols from the fruits of Hypericum henryi

  2016cites this paper
• Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms.

  2016cites this paper
• Unusual adamantane type polyprenylated acylphloroglucinols with an oxirane unit and their structural transformation from Hypericum hookerianum

  2016cites this paper
• Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes.

  2016cites this paper
• Hyperjapones A-E, Terpenoid Polymethylated Acylphloroglucinols from Hypericum japonicum.

  2016cites this paper
• Polycyclic Polyprenylated Derivatives from Hypericum uralum: Neuroprotective Effects and Antidepressant-like Activity of Uralodin A.

  2016cites this paper
• Strategien für die Synthese von Naturstoffen mit benachbarten stereogenen quartären Kohlenstoffatomen

  2016cites this paper
• The first total synthesis and the second- or third-generation approach

  2016cites this paper
• Domino Michael-aldol annulations for the stereocontrolled synthesis of bicyclo[3.3.1]nonane and bicyclo[3.2.1]octane derivatives

  2016cites this paper
• Total Synthesis of (-)-Nemorosone and (+)-Secohyperforin.

  2015cites this paper
• The enantioselective total synthesis of (+)-clusianone.

  2015cites this paper
• Direct and Transfer Hydrosilylation Reactions Catalyzed by Fully or Partially Fluorinated Triarylboranes: A Systematic Study

  2015cites this paper
• Total Synthesis of Hyperforin.

  2015cites this paper
• Hypercohin K, a polycyclic polyprenylated acylphloroglucinol with an unusual spiro-fused cyclopropane ring from Hypericum cohaerens

  2015cites this paper
• Polycyclic Polyprenylated Acylphloroglucinol Congeners Possessing Diverse Structures from Hypericum henryi.

  2015cites this paper
• Synthesis of highly strained bicyclic[3.n.1]alkenes by a metal-catalyzed Conia-ene reaction.

  2015cites this paper
• A Scalable Protocol for the Regioselective Alkylation of 2-Methylcyclohexane-1,3-dione with Unactivated sp3 Electrophiles

  2015cites this paper
• Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via catalytic asymmetric intramolecular cyclopropanation.

  2015cites this paper
• Construction of Bridged Polycyclic Systems by Polyene Cyclization.

  2015cites this paper
• Hypersubones A and B, new polycyclic acylphloroglucinols with intriguing adamantane type cores from Hypericum subsessile.

  2015cites this paper
• Total synthesis and absolute configuration assignment of MRSA active garcinol and isogarcinol.

  2015cites this paper
• Complex-Induced Proximity Effect in Lithiation: Unveiling RecentPotentials in Organic Synthesis of Biologically Relevant HeterocyclicCompounds

  2015cites this paper
• Biomimetic total synthesis of (±)-doitunggarcinone A and (+)-garcibracteatone.

  2014cites this paper
• Neurotrophic natural products: chemistry and biology.

  2014cites this paper
• Total synthesis of heronapyrrole C.

  2014cites this paper
• Synthesis of (+)-Luzofuran and (−)-Ancistrofuran

  2014cites this paper
• Rapid Synthesis of Polyprenylated Acylphloroglucinol Analogs via Dearomative Conjunctive Allylic Annulation

  2014cites this paper
• Asymmetric, stereodivergent synthesis of (-)-clusianone utilizing a biomimetic cationic cyclization.

  2014cites this paper
• The total syntheses of guttiferone A and 6-epi-guttiferone A.

  2014cites this paper
• Hyperuralones A and B, new acylphloroglucinol derivatives with intricately caged cores from Hypericum uralum.

  2014cites this paper
• Total syntheses of hyperforin and papuaforins A-C, and formal synthesis of nemorosone through a gold(I)-catalyzed carbocyclization.

  2014cites this paper
• Trying to rationalize total synthesis.

  2014cites this paper
• Chemistry and Biology of the Polycyclic Polyprenylated Acylphloroglucinol Hyperforin

  2014cites this paper
• Neurotrophe Naturstoffe – ihre Chemie und Biologie

  2014cites this paper
• Nature’s Antidepressant for Mild to Moderate Depression: Isolation and Spectral Characterization of Hyperforin from a Standardized Extract of St. John’s Wort (Hypericum perforatum)

  2014cites this paper
• Synthesis of medicinally relevant terpenes: reducing the cost and time of drug discovery.

  2014cites this paper
• New acylphloroglucinol derivatives with diverse architectures from Hypericum henryi.

  2014cites this paper
• An unusual Michael-induced skeletal rearrangement of a bicyclo[3.3.1]nonane framework of phloroglucinols to a novel bioactive bicyclo[3.3.0]octane.

  2013cites this paper