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Abstract
o-Quinone methide (o-QM) and o-naphthoquinone methide (o-NQM) are highly reactive intermediate that are widely applied in chemical, biological and engineering fields. The extraordinary reactivity of o-NQM towards nucleophiles (as in thiol-Michael addition) and dienophiles (as in Diels-Alder reaction), and its efficient and controllable generation through UV irradiation render o-NQM versatile practices in drug delivery, surface derivatization, and photolabile protecting group (PPG) development.The first part of the research focuses on developing various o-naphthoquinone methide precursors (NQMPs) for photo-controlled release of cargo in a site- and time-specific manner. Due to the ease of structure modification and photoreactive feature, the NQMPs were employed in drug delivery systems, by either being attached to other vehicles such as nanoparticles or as a prodrug itself to release H2S gasotransmitter. Particularly, comparing to the existing photo-activating H2S donors, the light-induced H2S release from NQMP-thiol or NQMP-disulfide showed a remarkable high yield (95%)
with the presence of simple thiols. An NQMP-thioether was also designed to generate “smart” surfaces through reversible derivatization. Additionally, NQMP-acetal was investigated as a PPG that release two equivalents of cargo molecule with 100% chemical yield and a high quantum yield of 0.26±0.01.
Azide-alkyne cycloaddition reactions have long been of great interest owing to the reaction efficiency and product stability. However, the existing methods have limitations such as rough reaction condition, use of toxic catalyst, or strenuous reactant preparation. To overcome these limitations, activated allenes were used in the cycloaddition in the second part of the research. These allenes were readily involved in cycloaddition reactions with azides. Comparing to the previous azide-alkyne cycloaddition reactions, this method worked in a catalyst free and regiospecific fashion while also benefit from convenient starting material preparation. Meanwhile, the oxidation of homopropargyl alcohols using Dess-Martin periodinane to synthesize activated allenes under mild condition also generated aryl furans with prolonged reaction time. This procedure provided a novel way of producing allenes or furans in one step without the use of organometallic catalysts.