Synthesis of Flavonoid Sulfates. II. The Use of Aryl Sulfatase in the Synthesis of Flavonol-3-sulfates*

There has been an increasing number of reports in recent years on the natural occurrence of flavonoid sulfates in the plant kingdom [2—21]. This considerable interest seems to be related to their suggested role in the detoxification of excess sulfate in response to high sulfur environment [2], From structural point of view, the naturally occurring flavonoid sulfates are derivatives of common hydroxyflavones (Fig. 1) and hydroxyflavonols (Fig. 2) or their methyl ethers. The recent development of a novel sulfotransferase assay [22] and the design of an original method for the synthesis of specifically sulfated compounds [1] allowed, for the first time, to demonstrate the enzymatic synthesis of flavonoid sulfate esters [23]. The method used for their organic synthesis utilized N,N'-dicyclohexylcarbodiimide (DCC) plus tetrabutylammonium hydrogen sulfate (TBAHS) and performed stepwise sulfation of positions 7, 4' and 3 of the flavonoid ring [1], It allowed the synthesis of a number of naturally occurring flavone-7-sulfates, as well as polysulfated flavonol-3-sulfates. In addition, the DCC-mediated sulfation afforded one major product that was easily separated from by-products by gel filtration [1], and therefore, represents a significant improvement of the previously described sul-