Abstract:

The first part of the talk will detail the synthesis of three collision induced dissociation cross-linkers that have been developed for cross-linking mass spectrometry experiments. One of the cross-linkers is a homobifunctional cysteine targeting linker. The two additional cross-linkers are heterobifunctional cross-linkers; one of which targets cysteine and lysine amino acids. The final cross-linker that will be discussed contains a diazirine ring that can be used for non-specific cross-linking, and was found to react with all twenty amino acids. These new cross-linkers expand the capability of studying protein structure and protein-protein interactions in tandem with mass-spectrometry.

The second part of the talk will detail the first total syntheses of strasseriolide A and B. Strasseriolide B exhibited potent antimalarial activity against the drug-sensitive and drug-resistant strains of malaria. The macrolides were synthesized through a convergent route targeting a carboxylic acid-aldehyde fragment and an alcohol-vinyl iodide fragment. The synthesis of the two fragments were completed by starting from commercially available terpenes. The fragments were coupled through a Yamaguchi esterification and the key macrocyclization event was accomplished via a Nozaki-Hiyama-Kishi cyclization. Strasseriolide B was synthesized in 16 steps (LLS) and strasseriolide A was synthesized in 17 steps (LLS).