53595-97-4Relevant academic research and scientific papers
New excursions into the synthesis and medicinal chemistry of the disulfide bond
Hunter, Roger,Kaschula, Catherine,Stellenboom, Nashia,Cotton, Jonathan,Parker, M. Iqbal
, p. 1497 - 1507 (2013/10/21)
The presentation discusses two themes of current interest in my research group in conjunction with a garlic mimics program. The first involves a new one-pot methodology for preparing unsymmetrical disulfides in high yield using 1-chlorobenzotriazole (BtCl) as oxidant, which can be applied to a range of functional types. The second part of the lecture will discuss the synthesis of derivatives of the garlic-derived natural product ajoene, in conjunction with an anti-cancer screening program. The synthesis has been used to prepare a fluorescently tagged derivative of the natural product that has been used to investigate localization and mode of action within the cancer cell using confocal laser scanning microscopy.
One-pot synthesis of unsymmetrical disulfides using 1-chlorobenzotriazole as oxidant: Interception of the sulfenyl chloride intermediate
Stellenboom, Nashia,Hunter, Roger,Caira, Mino R.
experimental part, p. 3228 - 3241 (2010/06/13)
A high-yielding and low temperature one-pot procedure is described for unsymmetrical disulfide synthesis from two different thiols using 1-chlorobenzotriazole (BtCl) as oxidant. The mechanism of the coupling involves in situ trapping of the sulfenyl chloride intermediate R1SCl by nucleophilic benzotriazole (BtH) to form R1SBt, which protects R1SCl from forming the homodimer R1SSR1. The methodology is applicable to all types of thiol (aliphatic, aromatic, heteroaromatic), with a variation developed for aliphatic-aliphatic couplings. Differentially N-protected cysteines couple to afford the unsymmetrical cystine derivatives in high yield (90%), which serves as a model for the one-pot intermolecular coupling of cysteine-containing peptides to form peptide disulfide heterodimers. Minimal exchange in aromatic-aromatic disulfide synthesis is noted on account of the mild conditions.
Effect of Charged Substituents on Rates of the Thiol-Disulfide Interchange Reaction
Hupe, D. J.,Wu, Dorothy
, p. 3100 - 3103 (2007/10/02)
Rate constants in aqueous solution at 25 deg C are reported for the production of p-nitrothiophenol from the mixed disulfides RSSC6H4NO2 upon reaction with the thiol anions R'S-.The R' groups used varied in charge and include -O2CCH2CH2, +H3NCH2CH2, and HOCH2CH2.The R groups used were these same three in addition to -O2CCH2CH2CH2.The solutions of RSSC6H4NO2 were prepared by allowing O2NC6H4S- to react with an excess of RSSR, followed by rapidly mixing R'S- and measuring the return of the absorption due to O2NC6H4S-.The rates for reactions involvingcharged R and R' groups differ from those with uncharged groups of identical pKa by factors of up to 2.5.Negatively charged groups, especially on the central thiol, slow the reaction and positively charged groups speed the reaction to a greater extent than that predicted by the calibrating ionization reaction.Ramifications of these observations are considered for the prediction of rate constants of thiol-disulfide interchange reactions and for the interpretation of β values when reactants of various charge types are used.
