| Summary: | The [2+2] photocycloaddition is a powerful but underused synthetic route to cyclobutanes. The underuse of this reaction can stem from unreliable yields, which can, in part, be attributed to secondary photoreactions of the desired product. The first part of this thesis describes investigations into new methods of trapping out primary photoproducts before secondary photoreactions can take place. Lithium borohydride was demonstrated as a successful trapping agent in intramolecular [2+2] enone-olefin photocycloadditions. Eight ketone products from the [2+2] photocycloaddition of vinylogous esters were trapped as their analogous alcohols, in moderate to good yields (27-83%). Without the conditions, the ketones were all afforded in lower yields (0-50%). This is the first example of the addition of a reducing agent to trap out products during the [2+2] photocycloaddition. Initial investigations into other trapping agents and trapping the products from other [2+2] photocycloadditions are discussed. Selective modification of proteins is a sought after goal in chemical biology. The second part of this thesis describes the use of bromomaleimide to selectively and reversibly label cysteine in small molecule substrates as thiomaleimides. Addition of a second thiol to the thiomaleimides can afford dithiosuccinimides, or addition of three equivalents of potassium carbonate in methanol can afford dehydroalanine motifs. Cysteine can be added to dibromomaleimide to afford bromothiomaleimides and dithiomaleimides. The thiomaleimides are photoactive and can be quantitatively dimerised to head-to-head trans adducts, or conjugated with a variety of olefins and alkynes. The regio- and diastereochemical outcomes of these reactions are discussed. The cyclobutanes thus formed render the modification irreversible to reductive conditions. The absorptions of thiomaleimides and their suitability for protein modification are considered very useful (>360 nm). A [2+2] photocycloaddition of styrene to RNAP sub-unit H was successful with good conversions, demonstrating the first use of this reaction to modify proteins.
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