Synthesis of Aza-Rocaglates via ESIPT-Mediated (3+2) Photocycloaddition

Wenyu Wang; Regina Cencic; Luke Whitesell; Jerry Pelletier; John A Porco Jr

doi:10.1002/chem.201602953

Synthesis of Aza-Rocaglates via ESIPT-Mediated (3+2) Photocycloaddition

Chemistry. 2016 Aug 16;22(34):12006-10. doi: 10.1002/chem.201602953. Epub 2016 Jul 15.

Authors

Wenyu Wang¹, Regina Cencic², Luke Whitesell³, Jerry Pelletier², John A Porco Jr⁴

Affiliations

¹ Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, 590 Commonwealth Avenue, Boston, MA, 02215, USA.
² Department of Biochemistry and The Rosalind and Morris Goodman Cancer Research Centre Room 810, McGill University, 3655 Drummond St., Montreal, QC, H3G 1Y6, Canada.
³ Whitehead Institute for Biomedical Research (WIBR), Cambridge, MA, 02142, USA.
⁴ Department of Chemistry, Center for Molecular Discovery (BU-CMD), Boston University, 590 Commonwealth Avenue, Boston, MA, 02215, USA. porco@bu.edu.

Abstract

Synthesis of aza-rocaglates, nitrogen-containing analogues of the rocaglate natural products, is reported. The route features ESIPT-mediated (3+2) photocycloaddition of 1-alkyl-2-aryl-3-hydroxyquinolinones with the dipolarophile methyl cinnamate. A continuous photoflow reactor was utilized for photocycloadditions. An array of compounds bearing the hexahydrocyclopenta[b]indole core structure was synthesized and evaluated in translation inhibition assays.

Keywords: ESIPT; flow chemistry; heterocycles; photocycloaddition; rocaglate.

Abstract

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