Total Synthesis and Absolute Configuration Determination of the α-Glycosidase Inhibitor (3S,4R)-6-Acetyl-3-hydroxy-2,2-dimethylchroman-4-yl (Z)-2-Methylbut-2-enoate from Ageratina grandifolia

Dandawate, Monica; Choudhury, Rahul; Krishna, G. Rama; Reddy, D. Srinivasa

doi:10.1021/acs.jnatprod.3c00236

Cited by 5 publications

(3 citation statements)

References 35 publications

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“…The calculated chemical shifts in CHCl 3 also agreed with the experimental data (Table S3). The negative optical rotation of 3 and synthetic 1 , recently reported, agreed …”

Section: Resultssupporting

confidence: 86%

“…A. grandifolia is sold in popular markets for treating diabetes, stomach complaints, and painful disorders . Previous investigation on this plant, collected in the State of Oaxaca, Mexico, led to the isolation of a few α-glucosidase inhibitors (flavonoids and chromenes), including the revised structure of 2,2-dimethyl-3 R -hydroxy-4 S -(1-angeloyloxy)-6-acetyl-chromane ( 1 ), recently synthesized. − …”

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confidence: 99%

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Calmodulin-Targeting Molecules from Ageratina grandifolia

Gutiérrez-González,

Pérez-Vásquez,

González-Andrade

et al. 2023

J. Nat. Prod.

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Four new natural chemical entities, including 2-hydroxy-α-truxillic acid (2), (3R,4S)-2,2-dimethyl-3-hydroxy-4-(1-angeloyloxy)-6-acetyl-7-methoxychromane (3), N-tricosanoyltyramine (4), and grandifolamide (5), were isolated along with 11 known compounds (1, 6–15) from the aerial parts of Ageratina grandifolia. The chemical structures were elucidated using chemical derivatization and HR-MS, NMR, and DFT-calculated chemical shifts, combined with DP4+ statistical analysis. It was found that 2 decomposed into its biogenetic precursor, o-coumaric acid, upon standing at room temperature for a few weeks. 3,5-Diprenyl-4-hydroxyacetophenone (8), O-methylencecalinol (10), encecalin (11), and encecalinol (12) bound to calmodulin (CaM) with higher affinity than chlorpromazine, a well-known CaM inhibitor. Molecular dynamics studies revealed that the complexes of these compounds with CaM remained stable during the simulation. Altogether these results revealed the therapeutic and research tool potential of compounds 8, 10, 11, and 12.

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“…The calculated chemical shifts in CHCl 3 also agreed with the experimental data (Table S3). The negative optical rotation of 3 and synthetic 1 , recently reported, agreed …”

Section: Resultssupporting

confidence: 86%

mentioning

confidence: 99%

Calmodulin-Targeting Molecules from Ageratina grandifolia

Gutiérrez-González,

Pérez-Vásquez,

González-Andrade

et al. 2023

J. Nat. Prod.

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“…In this study, we present the synthesis and the revision of the absolute stereochemistry of 2,2-dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane, a natural product obtained from A. grandifolia …”

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of Four Stereoisomers of 2,2-Dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane from Ageratina grandifolia and Plausible Absolute Stereochemistry of the Natural Product

Oh,

Im,

Bae

et al. 2023

ACS Omega

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2,2-Dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane is a natural product isolated from Ageratina grandifolia that exhibits inhibitory activity against yeast α-glucosidase. Initially, its structure was proposed to be 4-hydroxy-3-((S)-1′-angeloyloxy-(R)-2′,3′-epoxy-3′-methyl)butylacetophenone with an epoxide, but the structure was later revised to 2,2-dimethyl-3R-hydroxy-4S-(1-angeloyloxy)-6-acetylchromane. In this study, we present a total synthesis of 2,2-dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane from A. gradifolia and its stereoisomers. The key features of their synthesis include Sharpless asymmetric dihydroxylation of a readily available benzopyran substrate and subsequent Mitsunobu or Steglich reaction to provide both cis- and trans-isomers with chiral control. The absolute stereochemistry of the natural product was determined to be 2,2-dimethyl-3S-hydroxy-4R-(1′-angeloyloxy)-6-acetylchromane based on optical rotations of the synthesized compounds. The absolute configuration of the synthesized stereoisomers was confirmed by Mosher ester analysis. In addition, we provided ECD spectra for the four stereoisomers, which will allow verification of the absolute configuration of the natural product. Synthesis of all four stereoisomers of 2,2-dimethyl-3-hydroxy-4-(1′-angeloyloxy)-6-acetylchromane would facilitate the exploration of their potential biomedical applications.

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