Alkene syn- and anti-oxyamination with malonoyl peroxides

Malonoyl peroxide [6] is an effective reagent for the syn- or anti-oxyamination of alkenes. Reaction of [6] and an alkene in the presence of O-tert-butyl-N-tosylcarbamate (R3 = CO2tBu) leads to the anti-oxyaminated product in up to 99% yield. Use of O-methyl-N-tosyl carbamate (R3 = CO2Me) as the nitrogen nucleophile followed by treatment of the product with trifluoroacetic acid leads to the syn-oxyaminated product in up to 77% yield. Mechanisms consistent with the observed selectivities are proposed

Selective anti-Leishmanial Strathclyde minor groove binders using an N-oxide tail group modification

The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against L. donovani, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics

Metal-free di-functionalisation of alkenes with malonoyl peroxides

This thesis is restricted to Strathclyde users only until 5/04/2028This thesis describes the development of reactions for the di-functionalisation of alkenes using a malonoyl peroxide. Chapter 1 examines the development of the an anti-oxyamination reaction of alkenes using a malonoyl peroxide. The investigation examines both the substrate scope of the process and explores further chemistry of the oxyaminated products to form heterocyclic derivatives. Chapter 2 describes the attempts to difunctionalised alkenes using a sulfur nucleophile and a malonoyl peroxide. The first successful new C-S bond formation used p-toluenesulfinic acid as the sulfur nucleophile which was accompanied by a 1,2-phenyl migration. This reaction mechanism was investigated to try to understand the formation of this unexpected product. Sulfonyl thioamide and acythioamide were investigated as alternative sulfur nucleophiles, however, the oxidation of the sulfur nucleophile by malonoyl peroxide was unavoidable. To probe the oxidation of the sulfur nucleophile, malonoyl peroxide was reacted with stilbene to form an orthoester which was then reacted with our sulfur nucleophile, providing insight into the mechanistic course of the process.This thesis describes the development of reactions for the di-functionalisation of alkenes using a malonoyl peroxide. Chapter 1 examines the development of the an anti-oxyamination reaction of alkenes using a malonoyl peroxide. The investigation examines both the substrate scope of the process and explores further chemistry of the oxyaminated products to form heterocyclic derivatives. Chapter 2 describes the attempts to difunctionalised alkenes using a sulfur nucleophile and a malonoyl peroxide. The first successful new C-S bond formation used p-toluenesulfinic acid as the sulfur nucleophile which was accompanied by a 1,2-phenyl migration. This reaction mechanism was investigated to try to understand the formation of this unexpected product. Sulfonyl thioamide and acythioamide were investigated as alternative sulfur nucleophiles, however, the oxidation of the sulfur nucleophile by malonoyl peroxide was unavoidable. To probe the oxidation of the sulfur nucleophile, malonoyl peroxide was reacted with stilbene to form an orthoester which was then reacted with our sulfur nucleophile, providing insight into the mechanistic course of the process