Sulfur-enriched alkaloids from the root of Isatis indigotica

Five new sulfur-enriched alkaloids isatithioetherins A–E(1–5), and two pairs of scalemic enantiomers(t)-and( à)-isatithiopyrin B(6 a and 6 b) and isoepigoitrin and isogoitrin(7 a and 7 b), along with the known scalemic enantiomers epigoitrin and goitrin(8 a and 8 b), were isolated and characterized from an aqueous extract of the Isatis indigotica roots. Their structures were determined by extensive spectroscopic data analysis, including 2 D NMR and theoretical calculations of electronic circular dichroism(ECD) spectra based on the quantum-mechanical time-dependent density functional theory(TDDFT). Compounds 1–5 represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of 6 a and 6 b support the postulated biosynthetic pathways for the diastereomers 9 a and 9 b via a rare thio-Diels–Alder reaction. Compounds 2 and 4 showed antiviral activity against the influenza virus A/Hanfang/359/95(H3 N2, IC500.60 and 1.92 μmol/L) and the herpes simplex virus 1(HSV-1, IC503.70 and 2.87 μmol/L), and 2 also inhibited Coxsackie virus B3(IC500.71 μmol/L).& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Five new sulfur-enriched alkaloids isatithioetherins A–E（1–5）, and two pairs of scalemic enantiomers（t）-and（ à）-isatithiopyrin B（6 a and 6 b） and isoepigoitrin and isogoitrin（7 a and 7 b）, along with the known scalemic enantiomers epigoitrin and goitrin（8 a and 8 b）, were isolated and characterized from an aqueous extract of the Isatis indigotica roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism（ECD） spectra based on the quantum-mechanical time-dependent density functional theory（TDDFT）. Compounds 1–5 represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of 6 a and 6 b support the postulated biosynthetic pathways for the diastereomers 9 a and 9 b via a rare thio-Diels–Alder reaction. Compounds 2 and 4 showed antiviral activity against the influenza virus A/Hanfang/359/95(H3 N2, IC500.60 and 1.92 μmol/L) and the herpes simplex virus 1(HSV-1, IC503.70 and 2.87 μmol/L), and 2 also inhibited Coxsackie virus B3(IC500.71 μmol/L).