Total synthesis of (+)-sieboldine a: evolution of a pinacol-terminated cyclization strategy.
This article describes synthetic studies that culminated in the first total synthesis of the Lycopodium alkaloid sieboldine A. During this study, a number of pinacol-terminated cationic cyclizations were examined to form the cis-hydrindanone core of sieboldine A. Of these, a mild Au(I)-promoted 1,6-enyne cyclization that was terminated by a semipinacol rearrangement proved to be most efficient. Fashioning the unprecedented N-hydroxyazacyclononane ring embedded within the bicyclo[5.2.1]decane-N,O-acetal moiety of sieboldine A was a formidable challenge. Ultimately, the enantioselective total synthesis of (+)-sieboldine A was completed by forming this ring in good yield by cyclization of a protected-hydroxylamine thioglycoside precursor.
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, United States.
Stephen M
SM
Canham
David J
DJ
France
Larry E
LE
Overman
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; C484983:sieboldine A