1. Expeditious synthesis of polyacetylenic water hemlock toxins and their effects on the major GABA A receptor isoform.
- Author
-
Berger M, Chen Y, Bampali K, Ernst M, and Maulide N
- Subjects
- Biological Products chemical synthesis, Biological Products chemistry, Diynes chemical synthesis, Diynes chemistry, Fatty Alcohols chemical synthesis, Fatty Alcohols chemistry, Humans, Molecular Structure, Polyynes chemistry, Protein Isoforms drug effects, Protein Isoforms metabolism, Receptors, GABA-A chemistry, Water chemistry, Biological Products pharmacology, Diynes pharmacology, Fatty Alcohols pharmacology, Polyynes pharmacology, Receptors, GABA-A metabolism
- Abstract
Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABA
A receptor, including the structure-activity relationship of the derivatives.- Published
- 2018
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