Synthetic efforts towards the total synthesis of the Nucleoside Antibiotic, (+)-Amicetin

(+)-Amicetin is a hexopyranosyl cytosine, a relatively unexplored class of RNA-binding natural products, which are a sub-group of peptidyl transferase antibiotics. As a peptidyl transferase antibiotic, (+)-Amicetin acts as a universal antibiotic, however it has been shown to be particularly effective against Gram-positive and acid-fast bacteria, especially Mycobacterium, while having also shown antiviral activity. <br/><br/>Due to these properties (+)-Amicetin is of great interest, however to date there is no known total synthesis of (+)-Amicetin, and despite being known for several decades, few other hexopyranosyl cytosines have been synthesised in the lab. <br/><br/>While (+)-Amicetin was not synthesised within the given time, we believe that from a methodological perspective this work has revealed significant knowledge that could prove useful to whomever decides to assume the mantle next.<br/><br/>A number of routes were developed which lead to the amicetamine skeleton both via an α(1→4) glycosidic linkage strategy or starting from a maltoside with the key linkage pre-formed. Both of these routes provide different advantages, with one of the key goals in this project being the ability to synthesise analogues for future development. Both of these routes incorporate this belief, and allow for derivatisation at specific sites within the amicetamine fragment.<br/><br/>Further to this a route to the cytimidine fragment was well developed, with a limitation in the coupling sequence revealed of significant importance to any future chemist aspiring to synthesise (+)-Amicetin.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

Queen's University Belfast

Year dc:date.issued

2022

Author dc:creator

• Mackle, Ryan

Advisors dc:contributor.advisor

• De Silva, Amilra
• Muldoon, Mark

Language dc:language

eng

Identifier

oai:pure.qub.ac.uk/portal:studenttheses/699b19b0-6576-4d48-9592-93ba3c636bd4

OAI identifier oai:identifier

oai:pure.qub.ac.uk/portal:studenttheses/699b19b0-6576-4d48-9592-93ba3c636bd4