Synthesis of Substituted Pyrrolidines

• Main Author: Sjölin, Olof
• Format: Others
• Language: English
• Published: KTH, Skolan för kemivetenskap (CHE) 2016
• Subjects: Pyrrolidines; Multistep synthesis; Fragment-based drug design; Drug discovery; Organic chemistry; Organic Chemistry; Organisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-207056

The task of medicinal chemists in a drug discoveryproject is to synthesize/design analogues to the screening hits, simultaneouslyincreasing target potency and optimizing the pharmacological properties.  This requires a wide selection of moleculesto be synthesized, where both synthetic feasibility and price of startingmaterials are of great importance. In this work, a synthetic pathway from cheapand readily available starting materials to highly modifiable 2,4-disubstitutedpyrrolidines is demonstrated. Previously reported procedures to similarpyrrolidines use expensive catalysts, requires harsh conditions and requiresnon-commercially available starting materials. The suggested pathway herein has demonstrated great possibility forvariation in the 4-position, including fluoro, difluoro, nitrile and alcoholfunctional groups. There are several areas in which the synthesis can beimproved and expanded upon. Improvements can be made by optimizing thedescribed reaction conditions and further expansion of possible modificationsin both 2- and 4-position could be explored.