202595-96-8Relevant articles and documents
An enantioselective synthesis of cis perhydroisoquinoline LY235959
Hansen, Marvin M.,Bertsch, Carl F.,Harkness, Allen R.,Huff, Bret E.,Hutchison, Darrell R.,Khau, Vien V.,LeTourneau, Michael E.,Martinelli, Michael J.,Misner, Jerry W.,Peterson, Barry C.,Rieck, John A.,Sullivan, Kevin A.,Wright, Ian G.
, p. 775 - 785 (2007/10/03)
A novel synthesis of NMDA receptor antagonist LY235959 (1) has been achieved in 13% overall yield and 17 steps from (R)-pantolactone (7). Highlights of the synthesis include (a) use of a chiral auxiliary controlled asymmetric Diels - Alder reaction to provide the desired absolute and relative stereochemistry at C-4a, C-6, and C-8a, (b) an efficient alkylation of hindered iodide 13 using a novel amide benzophenone imine, (c) oxidative ring opening of the [2.2.2] bicyclic system to simultaneously functionalize the molecule for intramolecular cyclization and phosphonate introduction, and (d) an increased understanding of how the C-3 stereochemistry may be controlled by thermodynamic equilibration. Synthesis of epimer 20 in high overall yield makes this synthetic route attractive for future development efforts.
