Synthesis, Structure Revision, and Anti-inflammatory Activity Investigation of Putative Blumeatin

Abstract

Blumeatin, reported herein, bearing two hydroxyl groups at C3′ and C5′ of ring B, is isolated from the traditional Chinese medicine Blumea balsamifera. But the isolation procedure of blumeatin from plants has limitations of prolonged duration and high cost. A procedure featuring Lewis acid-catalyzed ring closure and chiral resolution via Schiff base intermediates is provided here to prepare optically pure blumeatin and its R-isomer efficiently. Furthermore, the structure revision of putative blumeatin based on a logically synthetic procedure and NMR spectroscopic analysis was conducted. The 1D and 2D NMR data analysis unambiguously confirmed our proposal that the reported blumeatin structure has been misassigned as it corresponds to sterubin, which contains two hydroxyl groups at C3′ and C4′ of ring B. Finally, the results of the ear-swelling test exhibited that synthetic (±)-blumeatin and (±)-sterubin had moderate anti-inflammatory activity which was less than that of (−)-sterubin.

Molecular Structure, Antioxidant Potential, and Pharmacokinetic Properties of Plant Flavonoid Blumeatin and Investigating Its Inhibition Mechanism on Xanthine Oxidase for Hyperuricemia by Molecular Modeling

“…Another recent publication by Xia et al in 2023 stated that blumeatin was synthesized and confirmed its hydroxyl groups at positions C-3′ and C-5′ by experimental NMR spectroscopy, and they only reported selected IR peaks rather than detailed individual vibrational modes as we present here. They also mentioned that the isolation procedure of this flavonoid from plants has limitations of prolonged duration and high cost …”

“…They also mentioned that the isolation procedure of this flavonoid from plants has limitations of prolonged duration and high cost. 106 …”

Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review

“…In vivo experiments on rodents demonstrated that blumeatin, isolated from B. balsamifera, protected liver against pathological changes induced by the carbon tetrachloride or thioacetamide intoxication [285]. Anti-inflammatory activity of the compound was confirmed in vivo by ear-swelling experiments on mice [279]. (+)-Dihydroquercetin (taxifolin) isolated from flowers of I. japonica demonstrated inhibitory activity against topoisomerase I (IC50 = 55.7 μM) and II (IC50 = 3.0 μM) [242].…”

“…In some cases sterubin was erroneously identified as blumeatin. The structure of the "putative blumeatin" was corrected by Xia et al 2023[279];2 Published as a metabolite of Inula cappa, corrected in 1984 by Goswami et al[280].…”

Evaluating the enantioselective capability of a cellulose tris(3,5‐dimethylphenyl carbamate)‐based stationary phase towards 5,7,2'‐trihydroxyflavanone

“…[ 6‐9 ] However, the HPLC method based on Cellulose tris(3,5‐dimethylphenyl carbamate) CSPs are not available to separate the single enantiomers of 5,7,2'‐trihydroxyflavanone (2'OH‐TFVN) efficiently whereas 4'‐OH‐TFVN was easily separable into its two enantiomers. [ 10,11 ]…”