Abstract
Several approaches to the spirochetes found in the marine neurotoxic agents, the gymnodimines, were studied. The strategy involved intermolecular Dials-Alder reactions of α-exomethylene lactones and lactams. A convergent racemic synthesis of the spirocyclic core structure of the gymnodimines was achieved in 7 linear steps and 16.4% overall yield from diethyl malonate. The key step in the synthesis was a Lewis-acid promoted intermolecular Dials-Alder reaction of an N-tosyl α-methylene []-lactam and a dienyne. The large scale synthesis of the dienophile (>30 g quantities available) was achieved in 5 steps from diethyl malonate in 30% overall yield and the synthesis of the diene (>20 g available) was achieved in 4 steps from propane in 38% overall yield. Large scale synthesis of the Diets-Alder adduct (4.5 g) has been achieved in 67% yield from the dienophile and diene precursors. Single crystal x-ray analysis of the Diels-Alder adduct confirmed that the radiochemistry and diastereoselectivity required for the gymnodimines was obtained.
Cohn, Stephen Todd (1999). A convergent intermolecular Diels-Alder approach to the spirocycles found in the marine neurotoxic agents, the gymnodimines. Master's thesis, Texas A&M University. Available electronically from
https : / /hdl .handle .net /1969 .1 /ETD -TAMU -1999 -THESIS -C66.