Date of Award

Summer 2017

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Mauro FA Adamo

Keywords

Chemistry, Pharmaceutical, Peptide Nucleic Acids

Abstract

Chapter 1

Overview of enantioselective desymmetrisations of prochiral and mesocompounds

A molecule is defined as prochiral when it can be converted to a chiral molecule in a single step. A meso-compound, on the other hand, is a molecule with multiple stereocentres superposable on its mirror image. Synthetic organic chemistry uses enantioselective desymmetrisation to convert prochiral or meso-compounds into chiral products. Herein, we reported an overview of desymmetrisation protocols of prochiral and meso-compounds developed over the past four decades.

Chapter 2

Development of organocatalytic desymmetrisation of aziridines: towards the synthesis of 4-methyl-N-(4-oxocyclopent-2-en-1- yl)benzenesulfonamide

Aziridine-containing products are chemical precursors for the preparation of carbocyclic nucleosides. In particular, carbonucleosides such as Carbovir, Abacavir, Aristeromycin, Entecavir and Neplanocin A, are the most targeted drugs for their anti-tumoral and antiviral (including anti-HIV and anti-hepatitis B) activities. Aziridines are saturated threemembered heterocycles containing one nitrogen atom. Ring strain renders aziridines susceptible to ring-opening reactions that dominate their chemistry, providing intermediates for the preparation of carbonucleosides. Herein, we reported the enantioselective desymmetrisation of meso-N-tosyl-aziridine to afford 4-methyl-N-(4- oxocyclopent-2-en-1-yl)benzenesulfonamide in up to 74% ee.

Chapter 3

Enantioselective Michael addition of diethylmalonate to cyclopent-1- enone catalysed by Cinchona alkaloid derivatives under phase-transfer catalysis

The Michael reaction is one of the most powerful tools in organic chemistry used in the formation of C-C bonds. The enantioselective Michael reaction further increases the scope of its application and establishes structural complexity in its products. We investigated the enantioselective Michael addition of diethylmalonate to cyclopenten-1- one catalysed by the Cinchona alkaloid family under phase-transfer catalytic conditions.

Chapter 4

Synthesis of novel peptide nucleic acids (PNAs) as candidate drugs for Neuroblastoma treatment

Peptide Nucleic Acids (PNAs) are DNA analogues in which the charged sugar-phosphate backbone, typical of DNA, is replaced by a neutral and achiral polyamide chain, composed of N-2-aminoethylglycine repeating units. Due to the presence of the natural pyrimidine and purine bases, PNAs are capable of following the Watson-Crick base pairing model. PNAs are chemically stable and resistant to hydrolytic (enzymatic) cleavage. It has been demostrated that PNAs are able to mimic the DNA duplex and interfere with every step in the replicative cycle of our genetic code. The unique hybridisation properties and the recognition of single-base mispairing in DNA make PNAs valuble as either a diagnostic tool for detecting genetic mutations or directly as anticancer drugs. Herein, we reported the synthesis of a novel PNA monomer with an improved chemical structure, tailored to enhance its binding mode and affinity towards the DNA duplex.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

File Size

11.3 MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2017.

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