| Summary: | The bioactive natural substance, hamamelitannin, was effectively synthesized in two ways. The chemical acylation of 2,3-<i>O</i>-isopropylidene-α,β-D-hamamelofuranose promoted by Bu<sub>2</sub>SnO using 3,4,5-tri-<i>O</i>-acetylgalloyl chloride, followed by the deprotection provided hamamelitannin in 79%. Pilot enzymatic benzoylation of D-hamamelose using vinyl benzoate (4 equiv.) and Lipozyme TL IM as a biocatalyst in <i>t</i>-butyl methyl ether (<i>t</i>-BuMeO) gave mainly benzoylated furanoses (89%), of which tribenzoates reached (52%). Enzymatic galloylation of 2,3-<i>O</i>-isopropylidene-α,β-D-hamamelofuranose with vinyl gallate under the catalysis of Lipozyme TL IM in <i>t</i>-butyl alcohol (<i>t</i>-BuOH) or <i>t</i>-BuMeO provided only the 5-<i>O</i>-galloylated product. The reaction in <i>t</i>-BuMeO proceeded in a shorter reaction time (61 h) and higher yield (82%). The more hydrophobic vinyl 3,4,5-tri-<i>O</i>-acetylgallate in the same reactions gave large amounts of acetylated products. Vinyl gallate and triacetylgallate in the enzymatic acylation of D-hamamelose with Lipozyme TL IM in <i>t</i>-BuMeO yielded 2′,5-diacylated hamamelofuranoses in a yield below 20%. The use of other vinyl gallates hydrophobized by methylation or benzylation provided 2′,5-diacylated hamamelofuranoses in good yields (65–84%). The reaction with silylated vinyl gallate did not proceed. The best results were obtained with vinyl 2,3,5-tri-<i>O</i>-benzyl gallate, and the only product, 2′,5-diacylated hamamelofuranoside precipitated from the reaction mixture (84% in 96 h). After debenzylation, hamamelitannin was obtained an 82% yield from hamamelose in two steps. This synthesis is preparatively undemanding and opens the way to multigram preparations of bioactive hamamelitannin and its analogues.
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