ao2c02117_si_001.pdf (1.71 MB)
Toward the Total Synthesis of Alpkinidine: Michael Addition to Isoquinolinetrione CE Ring-System Synthons
journal contribution
posted on 2022-06-01, 12:37 authored by Marco Buccini, Francis Dhoro, Louisa Tham, Brian W. Skelton, Craig M. Williams, Matthew J. PiggottStrategies toward
the total synthesis of the marine pyrroloacridine
alkaloid alpkinidine have been explored, focusing on linking quinonoid
CE ring-system synthons with the A ring, followed by condensation
to form the B and D rings. The key Michael addition of the ester enolate
derived from ethyl o-nitrophenylacetate to 2-methylisoquinoline-1,5,8(2H)-trione proceeded with the wrong regiochemistry. This
issue was addressed by incorporating the D-ring nitrogen at an earlier
stage, affording advanced intermediates possessing the complete carbon
skeleton of alpkinidine. However, attempts to close the D and B rings
were unsuccessful. The novel isoquinolinetriones reported here, and
the general strategy of connecting CE- and A-ring synthons through
Michael additions, may be useful in the synthesis of other pyrrolo-
and pyridoacridines, in particular the anticancer lead neoamphimedine
and analogues.
History
Usage metrics
Categories
Keywords
novel isoquinolinetriones reportedester enolate derivedcomplete carbon skeletonanticancer lead neoamphimedine>)- trione proceeded8 ( 2key michael additionisoquinolinetrione ce ringmichael additionconnecting cemichael additionswrong regiochemistrysystem synthonsring synthonsring nitrogengeneral strategyearlier stage>- nitrophenylacetate