Expanding the Synthetic Accessibility of Thiocarbamate (TCM) and Dithiocarbamate (DTCM) Donors for Hydrogen Sulfide (H2S) and Carbon Disulfide (CS2) Delivery
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Date
2024
Authors
Lutz, Rachel E.
Journal Title
Journal ISSN
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Publisher
University of Oregon
Abstract
The goal of this thesis is to bridge the gap in the literature by developing a suite of thiocarbamate and dithiocarbamate donor synthesis with azide and tert-butyl ester triggers. Based on previous work with esterase-triggered TCM H2S donors, we have developed a library H2S donors both with and without the nitrogen of the payload methylated, and have installed various EWGs and EDGs on the payload. Furthermore, we have developed a new method for modular TCM synthesis that supports diversification of the alkyl group of the aniline. This method allows us to block an unproductive deprotonation-based side pathway to more clearly study the effect of changing the payload electron density on the self-immolation of this donor motif. Blocking deprotonation of the payload expands the synthetic utility of these donors, which make them less reactive under basic conditions and allowing for more harsh synthetic conditions. Due to the ease of synthetic variation of the TCM donors, it is natural to consider broadening their application beyond H2S release to another biologically relevant molecule, CS2. Our TCM donor motif can yield this small molecule by designing the compound to contain a dithiocarbamate. Rather than releasing COS upon self-immolation, the donor should release CS2. Thus, I synthesized N-methylated CS2 DTCM donors using the same synthetic scheme as with methylated S-alkyl TCM donors.
Description
68 pages
Keywords
Synthesis, hydrogen sulfide, carbon disulfide, Nuclear Magnetic Resonance Spectroscopy