Hemiaminal derivatives of neothiobinupharidine

Abstract

6-and 6'-hydroxyneothiobinupharidine were isolated from Nuphar luteum from Poland. The presence of infrared Bohlmann bands, hydroxyl groups reduced by sodium borodeuteride, and the appearance of the pairs of peaks at mle 230 and 228 and 178 and 176 in the mass spectrum indicated the dual hemiaminal-amine nature of each of the two alkaloids. The 'H NMR signals at 6 4.57 given by the one isomer and at 6 4.08 given by the other demonstrated that the hemiaminal hydroxyl was located at a C-6 or C-6' position. On sodium borodeuteride reduction, singly labeled neothiobinupharidines were formed, that from the C-6 hemiaminal giving mle 179 but that from the C-6' hemiaminal giving m/e 178. The absence of the C-6 axial proton and the appearance of the C-6 equatorial proton as a singlet in the lH NMR indicated the presence of an axial deuterium at C-6 in neothiobinupharidine-6-dl. Similar evidence indicated that the deuterium atom in neothiobinupharidine-6'-dl was axial also. The CD of both hemiaminals in acid gave negative bands, the one from the C-6 hemiaminal appearing at 295 nm, and the one from the C-6' hemiaminal appearing at 279 nm.

Stable Hemiaminals with a Cyano Group and a Triazole Ring

“…For example the naturally occurring echinocandins possess a reactive hemiaminal group at the ornithine-5-position [14,15]. Some hemiaminals belonging to a neothiobinupharidine family were isolated from Nuphar luteum [16]. The hemiaminal functionality very often appears as an intermediate in biologically important enzymatic processes leading to Schiff-base formation [17,18,19].…”

Synthesis and Sulfur Electrophilicity of the Nuphar Thiaspirane Pharmacophore

“…No hemiaminal is observed in equilibrium even at −50 °C (see Supporting Information ), reflecting the stability of the Nuphar thiaspirane noted previously (see below). 15 − 17 However, addition of thiophenol to a solution of 13 ( Scheme 2 ) resulted in gradual formation of a single thiophenol adduct stable enough to be observed by liquid chromatography–mass spectrometry (LCMS). Complete removal of the volatile reaction components by evaporation over several hours delivered very pure starting material ( 13 ), indicating that if formation of disulfide 14 had occurred, it could also be rapidly reversed.…”

“…Simplified analogues that replace the thioether with a hydroxyl are also reported to lose all activity in fungicidal experiments . One explanation put forth for these structural requirements is the enhanced stability of the iminium adjacent to a thioether in 6-hydroxydimers (Figure b), − which may allow this otherwise strong carbon electrophile to penetrate the cell and reach a specific target . In contrast, the electrophilic promiscuity of the unstabilized iminium/hemiaminal of 6′-hydroxy dimers is thought to prevent access to a specific target .…”