Following the Lead from Nature: Divergent Pathways in Natural Product Synthesis and Diversity‐Oriented Synthesis

Sixteen polyketides belonging to diverse structural classes, including monomeric/dimeric tetrahydroxanthones and resorcylic acid lactones, were isolated from an organic extract of a fungal culture Setophoma terrestris (MSX45109) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, six were new: penicillixanthone B (5), blennolide H (6), 11-deoxy blennolide D (7), blennolide I (9), blennolide J (10), and pyrenomycin (16). The known compounds were: secalonic acid A (1), secalonic acid E (2), secalonic acid G (3), penicillixanthone A (4), paecilin B (8), aigialomycin A (11), hypothemycin (12), dihydrohypothemycin (13), pyrenochaetic acid C (14), and nidulalin B (15). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds 1–10 were determined using ECD spectroscopy combined with time-dependent density functional theory (TDDFT) calculations, while a modified Mosher’s ester method was used for compound 16. The cytotoxic activities of compounds (1–15) were evaluated using the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compounds 1, 4, and 12 were the most potent with IC50 values ranging from 0.16 to 2.14 μM. When tested against a panel of bacteria and fungi, compounds 3 and 5 showed promising activity against the Gram-positive bacterium Micrococcus luteus with MIC values of 5 and 15 μg/mL, respectively.

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“…RALs containing a ( Z )-enone have been reported as potent inhibitors of several ATPases and kinases, including TAK1. [31] …”

Section: Resultsmentioning

confidence: 99%

Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris

et al. 2014

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“…[9] Diversity oriented synthesis (DOS) is a strategy for quick access to molecule libraries with an emphasis on skeletal diversity. [10] One of the most important starting points for DOS is multicomponent reactions (MCRs): MCRs fill an important niche in library synthesis by providing direct access to library compounds.…”

Section: Graphical Abstractmentioning

confidence: 99%

The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

Dong

Song

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…[1] As opposed to target-oriented synthesis (Figure 1a), divergent synthesis is involves the designed construction of as eries of compounds from ac ertain intermediate (Figure 1b). [1] As opposed to target-oriented synthesis (Figure 1a), divergent synthesis is involves the designed construction of as eries of compounds from ac ertain intermediate (Figure 1b).…”

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confidence: 99%

“…[1] We start with the rational design of amodular covalent assembly protocol based on as uitable platform molecule.This molecule should be structurally rigid and symmetric,e asily available,a nd readily modified with (chiral) functionality and connectivity by reliable transformations.I deally,a sdepicted in Figure 1c,o nly two stages of covalent assembly from this platform molecule are necessary. [1] We start with the rational design of amodular covalent assembly protocol based on as uitable platform molecule.This molecule should be structurally rigid and symmetric,e asily available,a nd readily modified with (chiral) functionality and connectivity by reliable transformations.I deally,a sdepicted in Figure 1c,o nly two stages of covalent assembly from this platform molecule are necessary.…”

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confidence: 99%

Divergent Synthesis of Chiral Covalent Organic Frameworks

et al. 2019

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Featuring the simultaneous generation of alibrary of compounds from ac ertain intermediate,d ivergent synthesis has found increasing applications in the construction of natural products and potential medicines.I nspired by this approach, presented herein is ageneral strategy to introduce functionality, in ad ivergent manner,i nto covalent organic frameworks (COFs). This modular protocol includes two stages of covalent assembly,t hrough which functional COFs can be constructed by athree-step transformation of akey platform molecule,such as 4,7-dibromo-2-chloro-1H-benzo[d]imidazole (DBCBI). Constructed herein are four types of chiral COFs (CCOFs) from DBCBI by nucleophilic substitution, Suzuki coupling, and imine formation. The unique arrayofeight isoframework CCOFs allowed investigation of their catalytic performance and structure-activity relationship in an asymmetric amination reaction.

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Following the Lead from Nature: Divergent Pathways in Natural Product Synthesis and Diversity‐Oriented Synthesis

Cited by 65 publications

References 132 publications

Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris

Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris

The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

Divergent Synthesis of Chiral Covalent Organic Frameworks

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