The aim of this thesis was to prepare different synthetic cord factors (A, B, C and D) and understand how they affect the immune system, which relates to asthma and eczema.
Cord factors were made by esterification of a trehalose sugar and a mycolic acid using DMAP and 4-DMAP. At this first stage the esterification produced an anhydride mycolate which was first characterised and isolated.
The next step included silyl group deprotection m two steps first using
tetrabutylammonium fluoride to remove sugar silyl and then HF-pyridine complex to remove mycolic acid protection, releasing the free cord factor.
The aim of making such compounds was to be able to distinguish which specific
synthetic cord factors produce noticeable beneficial effects with the minimal side effects on a variety of chemokines and cytokines. In comparison, crude natural cord factors composed of a variety of components are toxic in different ways. A synthetic route mightbe able to separate inflammatory/toxic effects caused by some components and reveal beneficial effects of others.
Due the size of the molecules involved in a cord factor, a block by block synthesis was taken starting by making the mycolic acid (E, F) which were then incorporated to the cord factor.
A different type of molecule based on a glycerol core instead of the trehalose one has been proved to be bactericidal and to have anti-cancer properties (G). For this reason the synthesis of glycerol esters was included in the thesis as a different approach to disease treatment.
The final part of the thesis reports biological data obtained from synthetic cord factors and its implications with immune systems related illnesses.