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Total synthesis of the tetracyclic antimalarial alkaloid (±)-myrioneurinol
Anthony J Nocket1, Steven M Weinreb
1Department of Chemistry, The Pennsylvania State University, University Park, PA 16802 (USA).
Abstract:
The first total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid (±)-myrioneurinol has been accomplished using three highly diastereoselective reactions as pivotal steps: 1) an intramolecular Michael addition of a benzyloxycarbonyl-protected lactam titanium enolate to an α,β-unsaturated ester for construction of the spirocyclic C5 quaternary center and the a/d rings, 2) a malonate anion conjugate addition to a transient nitrosoalkene to install the requisite functionality and configuration at the C7 position, and 3) an intramolecular sulfonyliminium aza-Sakurai reaction to form the b ring and the attendant C9/C10 configuration of the natural product.
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