2,4-Dioxa-7-aza-, 2,4-Dioxa-8-aza-, and 2,4-Dioxa-9-aza-3-phosphadecalins as Rigid Acetylcholine Mimetics: Syntheses and Characterization

✍ Scribed by Stefan Furegati; Walter Ganci; Fabrizio Gorla; Urs Ringeisen; Peter Rüedi

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 665 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490236

✦ Synopsis

Abstract

Phosphorylation of suitable piperidine precursors yielded a series of novel decalin‐type O,N,P‐heterocycles. The title compounds, P(3)‐axially and P(3)‐equatorially X‐substituted, cis‐ and __trans‐__configurated 2,4‐dioxa‐7‐aza‐, 2,4‐dioxa‐8‐aza‐, and 2,4‐dioxa‐9‐aza‐3‐phosphabicyclo[4.4.0]decane 3‐oxides (X=Cl, F, 4‐nitrophenoxy, and 2,4‐dinitrophenoxy), are configuratively fixed and conformationally constrained P‐analogues of acetylcholine and as such represent acetylcholine (7‐aza and 9‐aza isomers) or γ‐homo‐acetylcholine mimetics (8‐aza isomers). Being irreversible inhibitors of acetylcholinesterase (AChE), the compounds are considered to be suitable probes for the investigation of the stereochemical course of the inhibition reaction by ^31^P‐NMR spectroscopy. Moreover, the design of these mimetics will enable studies of molecular interactions with AChE, in particular, the recognition conformation of acetylcholine.