Synthesis and inclusion studies of stable allicin mimics as novel antimicrobial agents

Includes abstract.Includes bibliographical references (p. 193-202).Allicin, a known constituent of garlic, is a potent but unstable antimicrobial agent. Consideration of the underlying features responsible for allicin’s activity, as well as its instability, prompted an investigation into substituted S-aryl alkylthiosulfinates as a class of potential allicin mimics with enhanced stability. Synthesis of the targets also inspired development of a novel unsymmetrical disulfide synthesis. This thesis describes the development of a new methodology for synthesizing unsymmetrical disulfides. The synthesis involves converting a thiol to a sulfenylating agent by 1-chlorobenzotriazole (BtCl) in the presence of 1,2,3-benzotriazole (BtH). Addition of a second thiol affords unsymmetrical disulfides in excellent yields. In addition to being a one-pot methodology, the approach offers attractive environmentally friendly and cost-saving aspects. The methodology proved to be versatile, producing all types of unsymmetrical disulfides; aromatic-aliphatic disulfides, aromatic-aromatic disulfides as well as aliphatic-aliphatic disulfides including unsymmetrical cysteine disulfides

Synthesis and inclusion of S-aryl alkylthiosulfinates as stable allicin mimics

S-Aryl alkylthiosulfinates showing aromatic rings with varying electronic demand have been prepared by oxidation of the corresponding disulfide, the latter prepared using new one-pot methodology involving thiol oxidation with 1-chlorobenzotriazole. Whereas thiosulfinates with electron-withdrawing substituents in the aromatic ring were unstable towards isolation, those with a releasing substituent in the para-position have shown good stability as potential allicin mimics and one of them (p-OMe) has been characterised as its inclusion compound in the cyclodextrin, TRIMEB, by X-ray crystallography