Haemanthamine is a member of the crinane-like family of Amaryllidaceae alkaloids. These compounds show a range of biological activities such as antiviral (including anti-HIV) and antitumor. They are also effective inhibitors of acetylcholinesterase, one of the leading targets against Alzheimer’s disease. Owing to their wide array of biological relevance, the crinane family of natural products has attracted the attention of biologists and synthetic chemists with several efforts towards their total synthesis. We aim to develop an efficient, practical and stereoselective synthesis of haemanthamine utilizing a recently developed multi-component reaction to form hydroxy-dihydro-pyrrolones. A subsequent reductive cyclization and ring closing metathesis provides the natural product scaffold while also affording the desired relative stereochemistry and regioselectivity required for many of the crinane-like alkaloids. This presentation will describe our efforts toward haemanthamine and related Amaryllidaceae alkaloids, with a focus on key reaction development enabling the synthesis of the target molecules and enabling pinpoint modifications for future chemical biology studies.

Stereoselective synthesis of haemanthamine and related Amaryllidaceae alkaloids

2019 Spring National Meeting

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