Concise and scalable synthesis of aspalathin, a powerful plasma sugar-lowering natural product

Journal of Natural Products
Ze HanJan H van der Westhuizen

Abstract

Aspalathin (1), a dihydrochalcone C-glucoside, exhibits powerful plasma sugar-lowering properties and thus potentially could be used to treat diabetes. Small quantities occur in rooibos tea, manufactured via fermentation of the leaves of Aspalathus linearis, hence necessitating the need for an efficient and concise synthesis. Efforts to synthesize aspalathin (1) via coupling of a glucose donor to the nucleophilic phloroglucinol ring of the dihydrochalcone moiety have invariably failed, presumably because of ring deactivation by the electron-withdrawing carbonyl group. Reduction of the carbonyl group of a chalcone (15) and coupling of the resulting 1,3-diarylpropane (16) to tetra-O-benzyl-β-D-glucopyranose afforded the C-glucosyl-1,3-diarylpropane (17). Regiospecific benzylic oxidation regenerated the carbonyl group and afforded the per-O-methylaspalathin (1a) quantitatively. This method was not successful with the per-O-benzyl-protected dihydrochalcone. However, the nucleophilicity of the phenolic hydroxy groups of the dihydrochalcone or its acetophenone precursor is not diminished by the carbonyl group. Thus, glucosylation of the di-O-benzylacetophenone (5c) at -40 °C afforded the α-O-glucoside (19) in 86% yield. Raising the t...Continue Reading

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Citations

Aug 28, 2015·Molecular Nutrition & Food Research·Sithandiwe E MazibukoChristo J F Muller
Oct 1, 2015·The Journal of Organic Chemistry·Vinod KhatriAshok K Prasad
Feb 2, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rabia JohnsonJohan Louw
Mar 31, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sandra BowlesChristo Muller
Apr 17, 2017·Carbohydrate Research·Nicolas PetryFrançoise Chrétien
Feb 22, 2018·Organic & Biomolecular Chemistry·Hongze LiaoXue-Wei Liu
Jan 19, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Phiwayinkosi V DludlaRabia Johnson
Feb 6, 2020·Molecular Nutrition & Food Research·Céline MoensLuc Bouwens
Jun 2, 2017·Organic & Biomolecular Chemistry·Midori A AraiMasami Ishibashi
Mar 31, 2019·Carbohydrate Research·Timothé VuckoSandrine Lamandé-Langle
Sep 16, 2017·Chemical Reviews·You Yang, Biao Yu

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