α,β-Unsaturated diazoketones as platforms in the asymmetric synthesis of hydroxylated alkaloids. Total synthesis of 1-deoxy-8,8a-diepicastanospermine and 1,6-dideoxyepicastanospermine and formal synthesis of pumiliotoxin 251D.
A versatile and concise approach for the stereoselective synthesis of mono-, di-, and trihydroxylated indolizidines is presented in four to six steps from Cbz-prolinal and a diazophosphonate. The key steps involved a Wolff rearrangement, followed by a stereoselective dihydroxylation/epoxidation reaction, from an α,β-unsaturated diazoketone. The strategy also permits extension to the synthesis of many natural hydroxylated indolizidine alkaloids as demonstrated in the formal synthesis of pumiliotoxin 251D.
Instituto de Química de São Carlos, Universidade de São Paulo, CEP 13560-970, São Carlos, SP, Brazil.
Barbara
B
Bernardim
Vagner D
VD
Pinho
Antonio C B
AC
Burtoloso
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D003979:Diazonium Compounds / Q000737:chemistry*; D006900:Hydroxylation; D054836:Indolizidines / Q000737:chemistry*; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
C578865:1,6-dideoxyepicastanospermine; C578866:1-deoxy-8,8a-diepicastanospermine; C517877:8-hydroxy-8-methyl-6-(2'-methylhexylidene)-1-azabicyclo(4.3.0)nonane; D000470:Alkaloids; D003979:Diazonium Compounds; D054836:Indolizidines; D007212:Indolizines