Total Synthesis of Acetylcholinesterase Inhibitor Macakurzin C

Abstract

A concise total synthesis of macakurzin C has been accomplished in nine steps (21% overall yield) from commercially available phloroglucinol, featuring a sequential aromatic Claisen rearrangement–cyclization.

Key words

total synthesis - natural products - aromatic Claisen rearrangement - acetylcholinesterase inhibitors - flavonoids

• References and Notes

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For a recent aromatic Claisen rearrangement, see:
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• 8 Under the reaction conditions, the benzoyl group in 6 was easily cleaved to afford bisphenol 16, which was rapidly propargylated to afford the C(7) propargyl ether 12.

For similar results on this type of aromatic Claisen rearrangement of flavone and isoflavone, see:
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• 10 We also prepared the corresponding MOM-, PMB-, and Bn-protected analogues of 17, which were tolerant to the reaction conditions. However, the C(5) propargyl ether groups were very susceptible to the various reaction conditions of deprotection, resulting in the decomposition of the starting materials.