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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis of the Core Tricyclic Ring Domain of (-)-Schulzeine B
Naoyuki Hoshiya1, Kenta Noda1, Yuji Mihara1
1†Department of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8412, Japan.
Abstract:
A formal synthesis of (-)-schulzeine B, a marine natural alkaloid possessing potent antidiabetic activity, has been achieved. A benzo[a]quinolizidin-4-one is a common skeleton of schulzeines (A-C). (-)-Schulzeine B possesses an (S)-stereogenic center at the C-3 carbon. The chiral (3S,11bS)-3-amino-9,11-dimethoxybenzo[a]quinolizidin-4-one has been prepared efficiently from (2-bromo-3,5-dihydroxyphenyl)acetonitrile in 17 steps including (i) a dehydrative intramolecular amination catalyzed by HClO4 and (ii) a proline or boric acid catalyzed transcycloamidation reaction for the construction of the δ-lactam ring.
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