MARKUS BAENZIGER*, CHRISTOPH BUCHER
*Corresponding author
Novartis Pharma AG, CH-4002 Basel, Switzerland

Abstract

The spiro cyclopropyl proline derivative (S)-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (1) is a key intermediate in the synthesis of active pharmaceutical compounds. An overview of our synthetic investigations will be presented herein. Three potential approaches have been identified: (a) starting from cyclopropyl-1,1-dimethanol from which the racemic amino acid can be built and then resolved, (b) starting from a pyroglutamic acid or (c) hydroxyproline building block where the spiro cyclopropyl ring has to be formed.

Introduction

The synthetic amino acid (S)-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (1) is a key intermediate for the synthesis of active pharmaceutical compounds. This amino acid is a key structural fragment of Ledipasvir (1), a highly active NS5A inhibitor. In recent estimate 120 – 130 million people are carrier of hepatitis C virus. Most of the infected individuals are not aware of the disease ... ...