Cyclopropenones in the synthesis of indolizidine, pyrrolo[2,1-a]isoquinoline and indolizino[8,7-b]indole alkaloids

Abstract

An attempted synthesis of the indolizidine natural product castanospermine resulted in the successful addition of cyclopropenone to a sugar-derived poly-hydroxylated cyclic imine to give an indolizidinone product, but with the installation of an extra hydroxy group at the castanospermine 8a -bridgehead position. This was also observed in our previous approach to the australine and hyacinthacine pyrrolizidine natural products. The same oxidative phenomenon occurred during the synthesis of pyrrolo[1,2- a ]isoquinolines from the reaction of aldimine dihydroisoquinolines with cyclopropenones, whereas ketimine based dihydroisoquinolines gave pyrrolo[1,2- a ]isoquinolines without bridgehead oxidation. These results may have some significance for the origins of the bridgehead hydroxy natural products jenamidine B 1 /B 2 , clazamycin A/B and legonmycin A/B. The precursor cyclic aldimine for the synthesis of the indolizino[8,7- b ]indoles gave dimeric indolizino[8,7- b ]indoles, whereas the corresponding cyclic ketimines behaved as expected and gave the indolizino[8,7- b ]indole core after reaction with cyclopropenones.