Alkaloids ofNuphar luteum

Synthesis and Sulfur Electrophilicity of the Nuphar Thiaspirane Pharmacophore

“…This latter compound proved difficult to isolate because the sulfurous reagents used for its synthesis caused retrodimerization to 7 upon acidification, concentration, and addition to silica (Figure a). These observations indicated that the final ring closure of the tetrahydrothiophene could be easily reversed via cleavage of the C–S bond, which surprised us since retrodimerization had not been previously reported in the extensive isolation literature. ,− However, this same tert -alkyl center undergoes epimerization upon heating in chloroform, which was rationalized by a stereoretentive epoxide formation and reopening by a pendant thiol (Figure , top pathway) . More likely, the presence of trace hydrochloric acid at high temperature induces iminium ion formation ( 8 ), whereby water or chloride anion attacks the thioether to form a sulfenic acid/enamine pair ( 9 ) that collapses to 2b after σ-bond rotation (bottom pathway) .…”

“…Subsequent amidation with 4-phenyl-butylamine occurred smoothly, as did lactam reduction with lithium aluminum hydride. While enamines similar to 11 were isolated in prior work, 25 we used crude solutions due to its sensitivity to water and oxygen. After some experimentation, we found that treatment of 11 with I 2 in a solution of dichloromethane at 0 °C effected tandem trityl removal 45 , 46 and oxidative cyclization to directly form iminium tetrahydrothiophene 13 .…”

Pharmacognostical Standardization of Rhizomes of Nuphar Luteum

“…Nuphar luteum (yellow water lily) is an aquatic plant of the family Nymphaeaceae, native to temperate regions of Europe, Northwest Africa, and Western Asia [1]. The dry rhizomes of N. luteum have yielded three sulfur-containing alkaloids: Thiobinupharidine, neothiobinupharidine, and nuphaleine (C30H42O4N2S) [2]. The root is astringent, demulcent, and anodyne.…”