Wulff Group Research Summary A major focus for our research group is the synthesis and biological evaluation of complex molecules that modulate protein-protein interactions. We currently have two main projects in this area. First, we are developing an iterative synthesis of a new class of beta-sheet mimetics that we will use to disrupt "face-on" b-sheet / b-sheet interactions like the PD1/PDL1 interaction. This interaction allows invading tumor cells to evade the body's natural immune response, and an increasing body of evidence suggests that its disruption would lead to new treatments for several human cancers. A second project concerns the total synthesis of didemnaketal A, a highly oxygenated polyisoprenoid that is thought to disrupt the intercalative b-sheet interface of the HIV protease dimer. While conducting research toward the synthesis of didemnaketal A, we discovered an intriguing bicyclic sulfone molecule that we are now developing as a new class of neuraminidase inhibitor (and thus a possible influenza treatment). This is now a third major project within the group. We frequently need to invent new reactions (or improve upon existing reactions) in order to reach our synthetic goals. As a result, we also have a number of purely methodology-driven projects, including a computational and experimental study of anionic oxy-cope reactions leading to 9-membered rings and the development of a new copper-mediated coupling of terminal alkynes with benzyl halides.