Abstract
5-Nor stemmadenine alkaloids, isolated from the genus Tabernaemontana, display a range of bioactivity. 16-Hydroxy-16,22-dihydroapparicine, the active component of an extract from the Tabernaemontana sp. (dichotoma, elegans, and divaricate), exhibited potent antimalarial activity, representing the first such report of the antimalarial property of 5-nor stemmadenine alkaloids. We, therefore, decided to attempt the total synthesis of the compound to explore its antimalarial activity and investigate structure and bioactivity relationships. As a result, we completed the first total synthesis of 16-hydroxy-16,22-dihydroapparicine, by combining a phosphine-mediated cascade reaction, diastereoselective nucleophilic addition of 2-acylindole or methylketone via a Felkin–Anh transition state, and chirality transferring intramolecular Michael addition. We also clarified the absolute stereochemistries of the compound. Furthermore, we evaluated the activity of the synthetic compound, as well as that of some intermediates, all of which showed weak activity against chloroquine-resistant Plasmodium falciparum (K1 strain) malaria parasites.
Highlights
Biologically Active Natural Products from Microorganisms and PlantsReceived: 25 April 2016 / Accepted: 14 May 2016 / Published online: 21 June 2016 Ó The Author(s) 2016
Occurring chemicals represent a treasure trove of compounds which hold promise as the seeds of discovery for drugs and medicines and which may facilitate the elucidation of structure and function investigations of bioactivity [1]
We evaluated the activity of the synthetic compound, as well as that of some intermediates, all of which showed weak activity against chloroquine-resistant Plasmodium falciparum (K1 strain) malaria parasites
Summary
Received: 25 April 2016 / Accepted: 14 May 2016 / Published online: 21 June 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com. Abstract 5-Nor stemmadenine alkaloids, isolated from the genus Tabernaemontana, display a range of bioactivity. 16-Hydroxy-16,22-dihydroapparicine, the active component of an extract from the Tabernaemontana sp. (dichotoma, elegans, and divaricate), exhibited potent antimalarial activity, representing the first such report of the antimalarial property of 5-nor stemmadenine alkaloids. We decided to attempt the total synthesis of the compound to explore its antimalarial activity and investigate structure and bioactivity relationships. We completed the first total synthesis of 16-hydroxy-16,22dihydroapparicine, by combining a phosphine-mediated cascade reaction, diastereoselective nucleophilic addition of 2-acylindole or methylketone via a Felkin–Anh transition state, and chirality transferring intramolecular Michael addition.
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