Studies toward the total synthesis of (–)-stolonidiol : a small molecule inducer of choline acetyltransferase

• Main Author: Barton, Thomas John
• Format: Others
• Language: English
• Published: 2012
• Subjects: Diterpene; Total synthesis; Knovenagel; Acrylate lynchpin
• Online Access: http://hdl.handle.net/2152/ETD-UT-2012-05-5237

The marine diterpene (–)-stolonidiol (1) has been shown to upregulate neuronal levels of acetylcholine. The mechanism through which a small molecule can impart this allosteric-like effect is currently unknown. A laboratory preparation of the natural product was undertaken in order to produce matieral for biological testing and elucidation of the unknown mechanism of action. During the course of this study, a tandem enyne-Suzuki reaction was investigated to form both rings of the fused bi-cyclic structure 26 in a single operation, but was met with undesired diastereoselectivity in the first cyclization step. The directing effect was found to be general on 1,6-homopropargyl enynes. Further efforts toward the molecule focused on an enantioselective formation of the cyclopentane core through an extension of a copper-mediated silylcyclization of epoxyalkyne 71. Using this intermediate two routes involving acrylate as a lynchpin to close the large ring were investigated. Additionally, a route designed to employ an intramolecular Knoevenagel condensation was explored to generate this ring system. === text