Comparison of (-)-eseroline with (+)-eseroline and dihydroseco analogs in antinociceptive assays: confirmation of rubreserine structure by x-ray analysis

Abstract

The enantiomers of eseroline bind to opiate receptors of rat brain membranes with equal affinities and show opiate agonist properties as inhibitors of adenylate cyclase in vitro. However, only (-)-eseroline shows potent narcotic agonist activity in vivo, similar to that of morphine. Neither (-)-noreseroline, (+)-eseroline, nor the open dihydroseco analogue (-)-8 shows analgetic effects in vivo. The structure of rubreserine being a resonance hybrid of an o-quinone with its zwitterionic mesomer is confirmed by solid-state X-ray diffraction analysis.

Phenserine and ring C hetero‐analogues: Drug candidates for the treatment of Alzheimer's disease

“…Treatment of the qua- ternary methoiodide with sodium borohydride in methanol readily gave the ring-open, indoline. 101 On heating phenserine to higher temperature one obtains physostigmole.…”

Phenserine, a Novel Anticholinesterase Related to Physostigmine: Total Synthesis and Biological Properties

“…AT-Llethylation of (19), the most cumbersome step in the syntliesis which was acconlplislled with the formation of tt Schiff base with benzaldehyde, its quaternization with methyl iodide, and hydrolysis of the quaternary salt, gave the secondary amine (20). The alnine (20) was resolved into its enantiomers. (-)-Eserethole (5a) was obtained by reduction of the enantiorner (20a) with sodium in ethanol.…”

“…in his time. succeeded in resolving the secondary aniine (20) into the enantiomers," this was difficult to reproduce,21 and it was preferred to resolve (f )-eserethole ( 5 ) , obtained on reduction of (20), with tartaric acid as reported by Kobayashi in 1934.l" A recent resolution of the primary anline (22) [5-0methyl ether ailalogue of (19) shown in Scheme 31 also greatly improved this route for technical purposes. nlyasthenia gravis, and in the experimental treatment of Alzheiiner's disease.…”

Current Progress in the Chemistry and Pharmacology of Akuammiline Alkaloids

“…Finally, 11,10'-biphenylic alkaloids rausutrine (1 1 0 ), and rausutranine (111), consisting of two akuammiline-type units, were isolated from the leaves of Rauwolfia sumatrana [48b]. Both bases comprise a unique oxidized A ring to iminoquinone, and diverge in the C-17/C-20 lactone that only exists in rausutranine (111). The configuration of the epoxide moiety present in rausutrine (110) was determined by the NOE measured between H-18/H-15 and H-19/H-21β; the identical stereochemistry was assigned to the analogous C-19/C-20 epoxide of cabufiline, which was not yet defined in the literature.…”

“…In 1992, Lewin et al disclosed the capacity of akuammine and its reduced derivative dihydroakuammine (124) [109] to bind µ-and κ-opioid receptors with low affinities in displacement studies of enkephalin analogues [110]. As shown with bold lines in Figure 8 , dihydroakuammine accommodates the hexahydropyrrolo[2,3-b]indole system existing in eseroline (125) [111], a derivative of physostigmine with strong opiod analgesic activities.…”