Utvikling av en ny metode for syntese av nitrosyklopropaner

Abstract

The physiological role of the serotonin receptor 5-ht1E is not yet understood, and little is known about its pharmacological effects. An aim of this project has been to establish a new synthetic route to potential 5-ht1E ligands, which will in turn enable a deeper understanding of this receptor. The target molecule is a conformationally rigid serotonin analog, containing a cyclopropane ring in the side chain.

A key step in this synthesis is the cyclopropanation of an alkene with nitromethane, via an in situ generated iodonium ylide. This reaction represents a novel method for the preparation of nitrocyclopropanes, and is a safer alternative compared to the use of nitro containing diazo compounds. The reaction has been developed and optimized using 2-vinylnaphthalene as a substrate. The optimal conditions give 2-(2-nitrocyclopropyl)naphthalene in 63 % yield, with 79 % conversion of 2-vinylnaphthalene. A variety of alkenes have been cyclopropanated by this method. The best yields are obtained with electron rich, sterically unhindered alkenes. With these alkenes, yields of about 50 % are obtained.