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Format:
Print
Author:
Cheng, Xiayun
Dept./Program:
Chemistry
Year:
2013
Degree:
PhD
Abstract:
The protecting group-free total syntheses of Lycopodium alkaloids nankakurines A and B have been accomplished in 6 and 7 steps, respectively, via a third Lycopodium alkaloid, luciduline. A 3-step highly stereo- and regioselective total synthesis of the alkaloid, luciduline is outlined. The key steps of this approach consist of a diethylaluminum chloride catalyzed Diels-Alder reaction, reductive amination and subsequent Mannich reaction to form the luciduline tricyclic skeleton. The first full 2D NMR spectral characterization was carried out on luciduline which further confirmed its structure. Using luciduline as a precursor, further aminoallylation, ring-closing metathesis and hydrogenation furnished nankakurine A, which was converted to nankakurine B by reductive methylation.
With the availability of luciduline and its analogs in sufficient quantities, an efficient asymmetric total synthesis of ( - )-Iyconadin C was achieved in 12 steps. This total synthesis features a short preparation of a luciduline congener, a ring expansion reaction and an assembly of a 2-pyridone. Extensive investigations were conducted on the regioselectivity of the ring expansion. The highlight of this synthetic route is the mild pyridone ring formation through a 6 [Pi]-electrocyclization reaction which is unprecedented for non-aryl isocyanates.
A total synthesis of the bridge-fused Aspidosperma indole alkaloid (±) has been accomplished in seven steps starting from the commercially available tryptamine. The bridge-containing scaffold of (±)-subincanadine F was efficiently assembled by a low valent titanium mediated intramolucular nucleophilic acyl substiutution (INAS) reaction. The synthetic utility of titanium-medicated INAS reagents for heterocyclic compounds was further demonstrated.