Walsh, Anthony (2015) Novel Methods to Access Bioactive Molecules. Doctoral thesis, University of Huddersfield.

This thesis is divided into two chapters detailing research on applying microwave methodology to access aminated nucleosides in significantly reduced time frames, and applying the Belluš-Claisen reaction to produce non-proteogenic dipeptides.
1. Amination of Nucleosides Using Microwave Methodology
2,2’-Anhydrouridine undergoes a ring opening reaction with aliphatic amines to give the corresponding aminated product. Under conventional heating reaction times are extremely lengthy, taking at least 3 to 4 days and up to a month in the case of very hindered amines. A modified procedure using microwave irradiation has proven to drastically reduce reaction time and has allowed access to novel nucleosides on gram scale.
2. Functionalised Amino Acids via the Belluš-Claisen Rearrangement
The Belluš-Claisen reaction is a [3,3] sigmatropic rearrangement of allylic amines, ethers and thioethers to give the corresponding amide, ester of thioester. A modified procedure of the Belluš-Claisen rearrangement was used to prepare functionalised dipeptides by reaction of a ketene prepared from N-phthaloylglycyl chloride in situ with allylic amino acid derivatives in the presence of a Lewis Acid and diisopropylethylamine. Rearrangments were successfully carried out using N,N-diallyl alanine and N-allyl proline. A range of N-allyl proline derivatives are demonstrated. However, attempts to repeat the reaction with structurally more complex amino acids did not result in successful reactions.

Walsh - final thesis.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (2MB) | Preview


Downloads per month over past year

Add to AnyAdd to TwitterAdd to FacebookAdd to LinkedinAdd to PinterestAdd to Email