Further studies on the application of vinylogous amides and β-halovinylaldehydes to the regiospecific synthesis of unsymmetrical, polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles

John T Gupton; Alex Shimozono; Evan Crawford; Joe Ortolani; Evan Clark; Matt Mahoney; Campbell Heese; Jeffrey Noble; Carlos Perez Mandry; Rene Kanters; Raymond N Dominey; Emma W Goldman; James A Sikorski; Daniel C Fisher

doi:10.1016/j.tet.2018.04.017

Further studies on the application of vinylogous amides and β-halovinylaldehydes to the regiospecific synthesis of unsymmetrical, polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles

Tetrahedron. 2018 May 24;74(21):2650-2663. doi: 10.1016/j.tet.2018.04.017. Epub 2018 Apr 7.

Affiliations

¹ Department of Chemistry, University of Richmond, Richmond, VA 23173, USA.
² Chemistry and Drug Discovery, Chesterfield, MO 63005, USA.
³ St. Christopher's School, Richmond, VA 23173, USA.

Abstract

Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also β-halovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles. Since the vinylogous amides and β-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology.

Keywords: Marine Natural Products; Pyrrole; Vinylogous Amide; β-Halovinylaldehyde.

Grants and funding

R15 CA067236/CA/NCI NIH HHS/United States