The Drug Synthesis Core will be established to support activities of Projects by Simpkins, Meyer, and Koulen in the Program. The role of the core for the progress of these projects is summarized in the following aims. Specific Aim 1. Synthesis of optimized antioxidant phenolic steroids for Project by Simpkins. Structure-activity studies carried out by us previously have indicated structural modifications that can be made to 17beta-estradiol that greatly enhance the neuroprotective potency of this steroid while at the same time decreasing or eliminating the compound's feminizing properties. The core will develop new synthetic methods that will provide additional compounds optimized for both neuroprotection and absence of feminizing actions. This core will also carry out the preparation of additional amounts of previously studied compounds. The continued availability of these compounds is essential for the mechanistic studies described in Project by Simpkins. Specific Aim 2. Synthesis of anabaseine compounds for Project by Meyer. Two specific aims in Project by Meyer require the availability of five different anabaseine derivatives. To ensure that supplies of these compounds remain available for study, the synthesis core will prepare additional supplies of these compounds. Previously reported synthetic methods will be used for preparation of the compounds. Specific Aim 3. Synthesis of modified NAEs for Project by Koulen. The facilities of the synthesis core will be utilized to undertake the preparation of a series of non-naturally occurring NAEs. The goal of preparing the new compounds is to extend the structure-activity studies undertaken in Project by Koulen.