1 research outputs found
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
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