Benwamycins A–G, Trialkyl-Substituted Benzene Derivatives from a Soil-Derived <i>Streptomyces</i>

Abstract

Seven new trialkyl-substituted benzene derivatives named benwamycins A-G (<b>1</b>-<b>7</b>), together with three known congeners, <b>8</b>-<b>10</b>, were isolated from culture broth of the soil-derived <i>Streptomyces</i> sp. KIB-H1471. Their structures were elucidated by using 1D and 2D NMR analyses in combination with HRESIMS data. The absolute configurations of <b>1</b>-<b>9</b> were determined by chemical conversion and comparison of circular dichroism spectra and confirmed for <b>1</b> by single-crystal X-ray crystallography. Compounds <b>6</b> and <b>7</b> have a unique γ-pyrone-like ring on one side chain. Compounds <b>2</b> and <b>6</b> inhibited human T cell proliferation with IC₅₀ values of 14.3 and 12.5 μM, respectively, without obvious cytotoxicity for naïve human T cells. Compounds <b>3</b> and <b>6</b> could weakly enhance insulin-stimulated glucose uptake.