The chemistry and biology of fungal meroterpenoids (2009–2019)

Organic & Biomolecular Chemistry, Год журнала: 2020, Номер 19(8), С. 1644 - 1704

Опубликована: Дек. 10, 2020

Fungal meroterpenoids are secondary metabolites from mixed terpene-biosynthetic origins. Their intriguing chemical structural diversification and complexity, potential bioactivities, pharmacological significance make them attractive targets in natural product chemistry, organic synthesis, biosynthesis. This review provides a systematic overview of the isolation, features, biological activities, fungal biodiversity 1585 novel 79 genera terrestrial marine-derived fungi including macrofungi, Basidiomycetes, 441 research papers 2009-2019. Based on nonterpenoid starting moiety their biosynthesis pathway, were classified into four categories (polyketide-terpenoid, indole-, shikimate-, miscellaneous-) with polyketide-terpenoids (mainly tetraketide-) shikimate-terpenoids as primary source. Basidiomycota produced 37.5% meroterpenoids, mostly shikimate-terpenoids. The Ganoderma, Penicillium, Aspergillus, Stachybotrys dominant producers. Moreover, about 56% display various pronounced cytotoxicity, enzyme inhibition, antibacterial, anti-inflammatory, antiviral, antifungal activities. It's exciting that several antroquinonol 4-acetyl B developed phase II clinically used drugs. We assume diversity therapeutic these will provide biologists medicinal chemists large promising sustainable treasure-trove for drug discovery.

Язык: Английский

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Charting the Evolution of Chemoenzymatic Strategies in the Syntheses of Complex Natural Products

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(33), С. 18161 - 18181

Опубликована: Авг. 8, 2023

Bolstered by recent advances in bioinformatics, genetics, and enzyme engineering, the field of chemoenzymatic synthesis has enjoyed a rapid increase popularity utility. This Perspective explores integration enzymes into multistep chemical syntheses, highlighting unique potential biocatalytic transformations to streamline complex natural products. In particular, we identify four primary conceptual approaches illustrate each with number landmark case studies. Future opportunities challenges are also discussed.

Язык: Английский

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Supramolecular coordination cages as crystalline sponges through a symmetry mismatch strategy

Nature Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Язык: Английский

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Total Synthesis of DMOA-Derived Meroterpenoids: Achieving Selectivity in the Synthesis of (+)-Berkeleyacetal D and (+)-Peniciacetal I

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

The synthesis of complex natural products requires efficient control over chemoselectivity, stereoselectivity, and regioselectivity. Berkeleyacetals, a subfamily 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids, pose substantial synthetic challenges due to their densely functionalized highly oxidized architectures, which have constrained efforts. Here, we present the first total this class DMOA-derived specifically (+)-berkeleyacetal D (+)-peniciacetal I. Our approach features chemoselective deprotonation followed by an intramolecular single-electron transfer (SET) from enolate alkyl bromide, enabling construction 2,3-dihydrofuran ring in berkeleyacetal D. Additional selective transformations include endo-selective Diels–Alder reaction, methylations semihydrogenation [3]dendralene, solvent-controlled diastereoselective epoxidation. Beyond providing route these congested products, our study offers mechanistic insights into achieving selectivity assembly architecturally demanding molecules.

Язык: Английский

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Chemistry of fungal meroterpenoid cyclases

Natural Product Reports, Год журнала: 2020, Номер 38(3), С. 566 - 585

Опубликована: Окт. 1, 2020

Covering: up to July 2020Fungal meroterpenoid cyclases are a recently discovered emerging family of membrane-integrated, non-canonical terpene cyclases. They catalyze the conversion hybrid isoprenic precursors towards complex scaffolds and therefore great importance in structure diversification biosynthesis. The products these pathways exhibit intriguing molecular highly potent bioactivities, making them privileged structures from Nature attractive candidates for drug development or industrial applications. This review will provide comprehensive comparative view on fungal cyclases, their chemistries scaffold formation step polycyclic natural products.

Язык: Английский

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Two Cytochrome P450 Enzymes Form the Tricyclic Nested Skeleton of Meroterpenoids by Sequential Oxidative Reactions

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Meroterpenoid clavilactones feature a unique benzo-fused ten-membered carbocyclic ring unit with an α,β-epoxy-γ-lactone moiety, forming intriguing 10/5/3 tricyclic nested skeleton. These compounds are good inhibitors of the tyrosine kinase, attracting lot chemical synthesis studies. However, natural enzymes involved in formation skeleton remain unexplored. Here, we identified gene cluster responsible for biosynthesis clavilactone A basidiomycetous fungus Clitocybe clavipes. We showed that key cytochrome P450 monooxygenase ClaR catalyzes diradical coupling reaction between intramolecular hydroquinone and allyl moieties to form unit, followed by ClaT exquisitely stereoselectively assembles moiety biosynthesis. unprecedentedly acts as macrocyclase catalyze oxidative cyclization isopentenyl nonterpenoid macrocycle, multifunctional ten-electron oxidation accomplish clavilactones. Our findings establish foundation efficient production using synthetic biology approaches provide mechanistic insights into macrocycle fungal meroterpenoids.

Язык: Английский

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Advanced crystallography for structure determination of natural products

Natural Product Reports, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Four cutting-edge crystallography strategies for structure elucidation of natural products that are difficult to crystallize or in nanocrystalline form.

Язык: Английский

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A Chiral-Pool-Based Strategy to Access trans-syn-Fused Drimane Meroterpenoids: Chemoenzymatic Total Syntheses of Polysin, N-Acetyl-polyveoline and the Chrodrimanins

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(43), С. 18280 - 18286

Опубликована: Окт. 20, 2021

trans-syn-Fused drimane meroterpenoids are unique natural products that arise from contra-thermodynamic polycyclizations of their polyene precursors. Herein we report the first total syntheses four trans-syn-fused meroterpenoids, namely polysin, N-acetyl-polyveoline, chrodrimanin C, and verruculide A, in 7–18 steps sclareolide. The unit is accessed through an efficient acid-mediated C9 epimerization Subsequent applications enzymatic C–H oxidation contemporary annulation methodologies install requisite C3 hydroxyl group enable rapid generation structural complexity to provide concise access these products.

Язык: Английский

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Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(16)

Опубликована: Фев. 7, 2022

Capitalizing on the late-stage diversification of an essential 1,3-diene intermediate, we describe herein a 9-step enantioselective total synthesis (+)-hyperforin and (+)-pyrohyperforin, starting from commercially available allylacetone. Our convergent features series critical reactions: 1) deconjugative α-alkylation α,β-unsaturated acid using chiral lithium amides as noncovalent stereodirecting auxiliaries; 2) HfCl4 -mediated carbonyl α-tert-alkylation to forge intricate bicyclo[3.3.1]nonane framework; 3) abiotic cascade pyran formation; 4) selective 1,4-semihydrogenation polyenes. During course our synthesis, also identified 1,2-cyclopropanediol overbred intermediate which was responsible for precursor formation through controlled fragmentation.

Язык: Английский

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Unified, Asymmetric Total Synthesis of the Asnovolins and Related Spiromeroterpenoids: A Fragment Coupling Approach

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(28), С. 12970 - 12978

Опубликована: Июль 6, 2022

3,5-Dimethylorsellinic acid (DMOA)-derived spiromeroterpenoids are a unique natural product family with attractive structures, unconventional stereochemistry, and potent biological activities. Herein, we report the first asymmetric total syntheses of asnovolins, DMOA-derived spiromeroterpenoids. The spirocyclic skeleton was efficiently assembled through sterically hindered bis-neopentyl 1,2-addition coupling/oxidative Michael addition sequence. unusual axial C12-methyl stereochemistry established via metal hydrogen atom transfer (MHAT) reduction involving chair-to-boat conformational change. mechanism HAT process studied both deuterium labeling computational studies. Attempted late-stage alkene isomerization an exocyclic enone proved to be challenging resulted in hetero-Diels–Alder dimerization, which ultimately led development alternative desaturation/coupling Endgame core modifications including orthogonal desaturation, Sc(III)-promoted regioselective Baeyer–Villiger oxidation, Meerwein–Ponndorf–Verley enabled collective five asnovolin-related products. This study demonstrates utility anionic fragment coupling assemble congested molecular framework provides foundation for synthesis spiromeroterpenoid congeners higher oxidation states

Язык: Английский

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