Celogentin C and theonellamide F are a class of natural products that have potential antimitotic behavior. They both contain interesting bicyclic structures with unusual linkages within a central moiety. Celogentin C's highly functionalized tryptophan moiety has two unusual linkages, a β-substituted Leu connection to the C6 of the indole structure that makes up the left-hand ring, and a τ-N connection of the imidazole to the C2 of the indole constructing the right-hand ring. This right-hand ring connection was solved via a novel oxidative coupling procedure developed in our group and the left-hand ring was initially constructed via a radical conjugated addition of an isopropyl group. Due to stereoselective concerns, our group explored hydrogen bond donors as potential catalyst candidates. Unfortunately, there were challenges in limiting the background reaction and obtaining reproducible results. We then designed an alternative route to solve this left-hand ring connection which would have utilized MacMillan asymmetric hydrogenation and α-chlorination procedures. Further work towards a second generation synthesis of the β-Leu-(C6)Trp connection was halted with the publication of two formal syntheses of celogentin C. Theonellamide F contains a τ-L-histidino-D-alanine (τ-HAL) bridging unit that separates the left-and right-hand rings. Previous efforts in the synthesis of this natural product were hindered due to an inefficient regioselective synthesis of τ-HAL. Our proposed synthesis of τ-HAL began with commercially available L- and D-Ser methyl esters which were then chemically transformed and coupled to one another to create a bis-amino subunit. Further preparations afforded us with an important cyclic intermediate which should readily lead to the first regioselective synthesis of a τ-HAL.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Robinson, Joshua Wayne, "Targeting Complex Cyclic Peptides for Synthesis: The Celogentin and Theonellamide Families" (2010). All Theses and Dissertations. 2536.
cyclic peptide, celogentin, theonellamide, tau-HAL