Romo, DanielYazdani, ZakariyaDr. Kenneth Hull, Dr. Haoran Xue2021-05-202021-05-2020212021-05-20https://hdl.handle.net/2104/11298Alzheimer’s Disease (AD) is responsible for the progressive brain degradation of 3 million U.S. citizens annually and is the sixth leading cause of death in America. This disease has no current cure. The goal of this project is to synthesize a novel neuroprotective derivative of gracilin A. Gracilin A is a unique metabolite derived from the marine sponge Spongionella gracilis and member of the spongiane diterpenoid family. The new molecule will act as a potent inhibitor of pathways responsible for oxidative damage to neurons directly precursing the onset of AD. Recently, derivatives of gracilin A were synthesized, analyzed, and determined to be potent neuroprotectors and immunosuppressants. These derivatives exhibit such effects by binding to cyclophilin D (CypD) thereby blocking opening of the mitochondrial permeability transition pore (mPTP). Docking experiments were performed to predict derivatives of gracilin A which would exhibit selectivity in binding to a CypD which blocks the mPTP and enhances neuroprotection over binding to Cyclophilin A (CypA). The compound proposed for total synthesis is based on a pre-existing mono-acetoxy furanose derivative of gracilin, compound 29a. The new molecule is characterized by the presence of a diol and absence of a gem dimethyl group.en-USBaylor University projects are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.Docking.Synthesis.Derivative.Gracilin.Affinity.Cyclophilin D.ThesisWorldwide access.Access changed 9/21/23.