Crystallization-Induced Diastereoisomer Transformation of Dihydroartemisinic Aldehyde with the Betti Base

Andrea Zanetti; Pauline Chaumont-Olive; Geoffrey Schwertz; Marllon Nascimento de Oliveira; Mario Andrés Gomez Fernandez; Zacharias Amara; Janine Cossy

doi:10.1021/acs.oprd.9b00481

Crystallization-Induced Diastereoisomer Transformation of Dihydroartemisinic Aldehyde with the Betti Base

Org Process Res Dev. 2020 May 15;24(5):850-855. doi: 10.1021/acs.oprd.9b00481. Epub 2020 Jan 14.

Authors

Andrea Zanetti¹, Pauline Chaumont-Olive¹, Geoffrey Schwertz¹, Marllon Nascimento de Oliveira², Mario Andrés Gomez Fernandez², Zacharias Amara², Janine Cossy¹

Affiliations

¹ Molecular, Macromolecular Chemistry and Materials, ESPCI Paris/CNRS/PSL Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France.
² Equipe Chimie Moléculaire, Laboratoire de Génomique, Bioinformatique et Chimie Moléculaire (GBCM), EA 7528, Conservatoire national des arts et métiers, HESAM Université, 2 rue Conté, 75003 Paris Cedex 03, France.

Abstract

Artemisinin is an important drug to fight malaria. It is produced either by extraction or via a semisynthetic route involving enzyme engineering. A key intermediate to produce artemisinin by the enzymatic route is dihydroartemisinic aldehyde (DHAAl). However, control of the absolute configuration of the stereocenter α to the aldehyde is highly challenging. Herein we report a protocol that allows the diastereomeric enrichment of a mixture of (11R)/(11S)-DHAAl to the desired (11R)-DHAAl by utilizing a crystallization-induced diastereomer transformation induced by the Betti base. In addition, the Betti base can be quantitatively recovered and reused after the reaction.