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

[摘要] 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. (C) 2020 Elsevier Ltd. All rights reserved.

[发布日期] 2020-11-07

[关键词] Indolizidine;Pyrroloisoquinoline;Indolizinoindole;Castanospermine;Cyclopropenone;Oxidation