Total synthesis of (+)-sieboldine A.
The first total synthesis of (+)-sieboldine A was completed in 20 steps from readily available (3aS,6aR)-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one (5). Key steps are as follows: (a) a pinacol-terminated 1,6-enyne cyclization reaction to form the cis-hydrindanone core (11 --> 12), (b) formation of the spiro tetrahydrofuran ring by stereoselective DMDO oxidation of tricyclic dihydropyran intermediate 15, and (c) formation of the unprecedented N-hydroxyazacyclononane ring by cyclization of a thioglycoside precursor (18 --> 19).
Canham
Stephen M
SM
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
France
David J
DJ
Overman
Larry E
LE
D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D006576:Heterocyclic Compounds, 4 or More Rings; C484983:sieboldine A