Drimane-Related Merosesquiterpenoids, a Promising Library of Metabolites for Drug Development

Shan, Wei‐Guang; Ying, You‐Min; Ma, Lie‐Feng; Zhan, Zha‐Jun

doi:10.1016/b978-0-444-63473-3.00006-x

Cited by 13 publications

(19 citation statements)

References 464 publications

(422 reference statements)

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“…Biosynthetic pathways in fungi were responsible for metabolites with diverse chemical structures and a wide range of biological activities that have fascinated scientists for decades. , However, the natural and ecological functions of most of these biosynthetic pathways have remained unclear. The PKS–TPS hybrid pathways were involved in the biosynthesis of a unique family of SECs that were widely distributed in common plant pathogenic fungi, including Aspergillus , Penicillium , and Byssochlamys species and the predominant nematode-trapping fungus A. oligospora .…”

Section: Discussionmentioning

confidence: 99%

“…24 and notorious phytotoxic macrophorins (5 and 6) from the fungus Macrophoma causing fruit rot of apples (Figure 1). 25 These metabolites have attracted considerable interest from biologists, pharmacologists, and synthetic chemists for their diverse biological activities. 24,25 However, the natural and ecological functions of this family of metabolites in fungal adaptation and colonization in diverse environments was still lacking.…”

Section: ■ Introductionmentioning

confidence: 99%

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Polyketide Synthase–Terpenoid Synthase Hybrid Pathway Regulation of Trap Formation through Ammonia Metabolism Controls Soil Colonization of Predominant Nematode-Trapping Fungus

Wang

et al. 2021

J. Agric. Food Chem.

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Polyketide synthase−terpenoid synthase (PKS−TPS) hybrid pathways for biosynthesis of unique sesquiterpenyl epoxy-cyclohexenoids (SECs) have been found to be widely distributed in plant pathogenic fungi. However, the natural and ecological functions of these pathways and their metabolites still remain cryptic. In this study, the whole PKS−TPS hybrid pathway in the predominant nematode-trapping fungus Arthrobotrys oligospora was first proposed according to all the intermediates and their derivatives from all the A. oligospora mutants with a deficiency in each gene involved in SEC biosynthesis. Most mutants displayed significantly increased trap formation which was correlated with alteration of the ammonia level. Further analysis revealed that the main metabolites involved in ammonia metabolism were largely increased in most mutants. However, significantly retarded colonization in soil were observed in most mutants compared to the wild-type strain due to significantly decreased antibacterial activities. Our results suggested that A. oligospora used the PKS−TPS hybrid pathway for fungal soil colonization via decreasing fungal nematode-capturing ability. This also provided solid evidence that boosting fungal colonization in soil was the secondary metabolite whose biosynthesis depended on a PKS−TPS hybrid pathway.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Polyketide Synthase–Terpenoid Synthase Hybrid Pathway Regulation of Trap Formation through Ammonia Metabolism Controls Soil Colonization of Predominant Nematode-Trapping Fungus

Wang

et al. 2021

J. Agric. Food Chem.

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“…We next mainly focused on the multi substituted aromatic halides with alkoxyl groups, which were prevalent in the natural drimane hydroquinones. [4][5] The resulting coupled 37, X = Br, 86% X = I, 60% products can serve as versatile precursors for the expedite construction of natural products themselves or mimics. To our delight, the coupling paradigm went smoothly under the optimized conditions providing a number of yahazunol analogues or the precursors of the related drimane meroterpenoids in good to excellent yields (48-59).…”

Section: Combination Of Decarboxylative Borylation and Suzukimentioning

confidence: 99%

“…3 Drimane (hydro)quinones (Scheme 1A) are a large family of secondary metabolites from mixed biogenesis of polyketide-terpenoids origins. 4 Decoration or tiny modification on either the aromatic ring or drimane segment of the common scaffold 1, will lead to vast swaths of natural products (Scheme 1A) possessing a wealth of bioactivities, 5 ranging from anti-inflammatory, anti-HIV, antitumor, antiviral, antimalarial to antifungal potentials. This kind of natural products showed a tremendous advantage as an ideal model in drug discovery in the view of a structural standpoint by assembling the preinstalled stereospecific sp 3 hybridized skeleton with sp 2 hybridized aromatic equivalents.…”

Section: Introductionmentioning

confidence: 99%

Facile and Divergent Synthesis and Antifungal Evaluation of Drimane Meroterpenoids by Merging Decarboxylative Borylation and Suzuki Coupling

Wang¹,

Zhang²,

Cui³

et al. 2020

Preprint

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Based on the easily accessible and inexpensive sclareol, the bench stable drimanyl BPin was achieved through oxidative degradation and decarboxylative borylation. The following Suzuki coupling of the borate intermediate was developed as a powerful platform for a large variety of drimane meroterpenoids, non-natural mimics and ring-distorted motifs. Key features include mild conditions, operational facility, broad substrate scope, scalability, and good chemofidelity and stereofidelity as well as the easy availability of the various coupling partners. Expedient formal synthesis of a large number of complex natural products is feasible via the current methodology. The high degree of practicality of the current chemistry bodes well for the discovery sciences towards pharmaceutically important meroterpenoids or leads through detailed SAR study. The facile accessibility to drimane meroterpenoids and mimics allowed the unprecedented evaluation of these chemical entities as antifungal agents. The promising activity of the non-natural mimics may open a new window for structural optimization and the identification of new targets.

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“…Natural products occupied an irreplaceable role in the discovery of therapeutically important entities due to their unique biological profiles or uncharted chemotypes . Drimane (hydro)quinones (Figure A) make up a large family of secondary metabolites from mixed biogenesis of polyketide–terpenoid origin . These natural products showed a tremendous advantage as an ideal model for drug discovery from a structural standpoint by assembling an sp 3 -hybridized skeleton with sp 2 -hybridized aromatic units.…”

mentioning

confidence: 99%

Modular Synthesis of Drimane Meroterpenoids Leveraging Decarboxylative Borylation and Suzuki Coupling

et al. 2020

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Drimane meroterpenoids have attracted an increasing amount of attention in the discovery of therapeutically important probes, while the laggard synthetic accessibility is a conspicuous challenge. A new paradigm merging decarboxylative borylation and Suzuki coupling was developed as a powerful platform. Key features include the mild conditions, good chemoselectivity, operational facility, scalability, and easy availability of the coupling partners. This practical strategy enables the expedient formal synthesis of a large number of natural products and rapid generation of analogues.

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Drimane-Related Merosesquiterpenoids, a Promising Library of Metabolites for Drug Development

Cited by 13 publications

References 464 publications

Polyketide Synthase–Terpenoid Synthase Hybrid Pathway Regulation of Trap Formation through Ammonia Metabolism Controls Soil Colonization of Predominant Nematode-Trapping Fungus

Polyketide Synthase–Terpenoid Synthase Hybrid Pathway Regulation of Trap Formation through Ammonia Metabolism Controls Soil Colonization of Predominant Nematode-Trapping Fungus

Facile and Divergent Synthesis and Antifungal Evaluation of Drimane Meroterpenoids by Merging Decarboxylative Borylation and Suzuki Coupling

Modular Synthesis of Drimane Meroterpenoids Leveraging Decarboxylative Borylation and Suzuki Coupling

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