Continuous Flow Synthesis of alpha-Haloketones – Essential Building Blocks of Antiretroviral Agents
Conference Recording Jul 14, 2014
About the SpeakerC. Oliver Kappe is Professor of Organic Chemistry and Director of the Christian Doppler Laboratory for Microwave Chemistry (CDLMC) at the University of Graz, Austria. C. Oliver Kappe is currently Editor-in-Chief of the Journal of Flow Chemistry (Akadémiai Kiadó) and a member of the Flow Chemistry Society. He is also a board member of the International Society of Heterocyclic Chemistry and The Society of Combinatorial Sciences. In addition he has been an Editor of the Journal QSAR and Combinatorial Sciences (Wiley-VCH, 2003-2007) and has served/serves on the Editorial/Advisory Boards of the Journal of Combinatorial Chemistry (ACS), Molecular Diversity (Springer), ChemMedChem and ChemSusChem (Wiley-VCH), Journal of Heterocyclic Chemistry (Wiley-VCH) and a number of other journals.AbstractIn the last two decades a series of highly potent, orally bioavailable viral protease inhibitors have gained approval for HIV treatment. HIV protease inhibitors are commonly used together with reverse transcriptase inhibitors for highly active antiretroviral therapy (HAART). Viral protease inhibitors, such as Atazanvir and Saquinavir are listed by the World Health Organization as essential medicines for a basic health care system. The protease inhibitors are peptidomimetics, resembling substrates in which the scissile bond is replaced by a nonhydrolyzable hydroxyethylene or hydroxyethylamine structure. In fact, most of the approved HIV protease inhibitors contain a chiral aminoalcohol structure in the central core. In this presentation the three step continuous flow synthesis of the chiral aminoalcohol motif required for the preparation of Atazanavir will be described. This requires the continuous generation of anhydrous diazomethane from the respective amino acid. Diazomethane is a volatile, highly irritating, poisonous and carcinogenic compound and furthermore is exceedingly heat-, light- and shock sensitive and tends to decompose explosively. A safe continuous strategy that relies on membrane separation technology for the preparation of anhydrous diazomethane will be described in this presentation.