%0 Generic
%9 Master's Thesis
%A Lizza, Joseph
%D 2020
%F pittir:38135
%K peptides, cycloaddition, natural products
%T DEVELOPMENT OF THE 2,2,6,6-TETRAMETHYLPIPERIDIN-1-YLOXYCARBONYL (TEMPOC) PROTECTING GROUP AND EFFORTS TOWARDS THE TOTAL SYNTHESIS OF α-CYCLOPIAZONIC ACID
%U http://d-scholarship-dev.library.pitt.edu/38135/
%X The 2,2,6,6-Tetramethylpiperidin-1-yloxycarbonyl (Tempoc) protecting group is a new carbamate protecting group for various types of amines. Installation can be accomplished using the new reagent 4-nitrophenyl (2,2,6,6-tetramethylpiperidin-1-yl) carbonate (NPTC) under mild conditions. Tempoc is stable under strongly acidic and basic conditions, and displays orthogonal deprotection properties when used in tandem with the tert-butyloxycarbonyl (Boc) and benzyloxycarbony (Cbz) protective groups. Deprotection can be accomplished under thermolytic conditions at 135 °C, or under reductive conditions with in situ generated catalytic Cu(I). Furthermore, Tempoc has also been shown to be a useful protecting group in peptide synthesis. Protecting a broad range of biologically relevant amino esters has been accomplished in the presence of 1-hydroxybenzotriazole (HOBt) as an NPTC activator. Demonstration of Tempoc utility has been realized through the synthesis of a tripeptide fragment of Gramicidin S, a cyclic decapeptide that possesses antimicrobial activity. Unrelated, efforts toward the total synthesis of α-Cyclopiazonic acid are also discussed. The ambitious 1,3-dipolar cycloaddition of a highly substituted aziridine with relatively unactivated dipolarophiles led to interesting results that may be useful for the synthesis of other complex biologicals and natural products.