α‑Glucosidase Inhibitors from a <i>Xylaria feejeensis</i> Associated with <i>Hintonia latiflora</i>
2015-04-24T00:00:00Z (GMT) by
Two new compounds, pestalotin 4′-<i>O</i>-methyl-β-mannopyranoside (<b>1</b>) and 3<i>S</i>,4<i>R</i>-(+)-4-hydroxymellein (<b>2</b>), were isolated from an organic extract of a <i>Xylaria feejeensis</i>, which was isolated as an endophytic fungus from <i>Hintonia latiflora.</i> In addition, the known compounds 3<i>S</i>,4<i>S</i>-(+)-4-hydroxymellein (<b>3</b>), 3<i>S</i>-(+)-8-methoxymellein (<b>4</b>), and the quinone derivatives 2-hydroxy-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (<b>5</b>), 4<i>S</i>,5<i>S</i>,6<i>S</i>-4-hydroxy-3-methoxy-5-methyl-5,6-epoxycyclohex-2-en-1-one (<b>6</b>), and 4<i>R</i>,5<i>R</i>-dihydroxy-3-methoxy-5-methylcyclohexen-2-en-1-one (<b>7</b>) were obtained. The structures of <b>1</b> and <b>2</b> were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of the stereogenic centers of <b>1</b> and <b>2</b> was determined using ECD spectroscopy combined with time-dependent density functional theory calculations. In the case of <b>1</b>, comparison of the experimental and theoretical <sup>3</sup><i>J</i><sub>6–7</sub> coupling constants provided further evidence for the stereochemical assignments. Compounds <b>2</b> and <b>3</b> inhibited <i>Saccharomyces cerevisiae </i>α-glucosidase (αGHY), with IC<sub>50</sub> values of 441 ± 23 and 549 ± 2.5 μM, respectively. Their activity was comparable to that of acarbose (IC<sub>50</sub> = 545 ± 19 μM), used as positive control. Molecular docking predicted that both compounds bind to αGHY in a site different from the catalytic domain, which could imply an allosteric type of inhibition.