Synthesis of 2,3,4-13C-labeled isoflavone 7-O-glucosides

Abstract

The current body of research on the health implications of isoflavone phytoestrogens still presents unsolved matters pertaining to absorption, metabolism, and bioavailability. To conduct research in this particular domain, it is important to possess the means to obtain samples of both isoflavone 7-O-glucosides, which are naturally occurring in plants, and 7-O-glucuronides, which are major metabolites present in mammals. To comprehensively examine the potential health advantages, it is important to precisely measure the concentrations of phytoestrogens present in various food sources and bodily fluids. The use of C-labeled isoflavones was critical to the development of a methodology that allows for precise measurement. 2,3,4-¹³C-Labeled isoflavone 7-O-glucosides, namely 2,3,4-¹³C-labeled daidzin, genestin and glycitin, were efficiently prepared via BF₃·Et₂O catalyzed glycosylation at the 7-O-position of ¹³C-labeled 4′-O-hexanoyldaidzein, 4′-O-hexanoylglycitein and 5,4′-O-dihexannoylgenestein with 2,2,2-trifluoro-N-(p-methoxyphenyl)acetamidates as glycosyl donors. It was found that protecting all of the OH groups in the isoflavones with hexanoyl groups, with the exception of the 7-OH group, resulted in an increase in both their solubility in organic solvents and the reaction efficiency.