Abstract
We have explored a novel method to synthesize chiral aziridines which are potential precursors for nitrogen-containing natural products. Here, we presesnt synthetic approaches to polyhydroxylated pyrrolidine alkaloids such as DMDP (1) and 1-epiaustraline (2) using aziridine ring-opening reaction with O-nucleophile followed by iodoamination as key reaction steps. Stereospecific ring-opening reaction of cis- and trans-aziridines 5, obtained with about 80% ee, with AcOH or Ts0H/H_20 smoothly proceeded with inversion to give syn- and anti-derivatives, respectively. Iodoamination of syn-10 and -11 in dichloromethane afforded cis, cis, trans-pyrrolidine system 12 with high diastereoselectivity, while in the case of anti-derivatives lower selectivity was observed under the same conditions. The lower selectivity was improved by the use of ethyl acetate as a solvent. For approach to DMDP (1), successive treatments of all trans-iodopyrrolidine 15a with AcOAg, LiBH_4 and TBAF afforded a tetraol 22 but not an intended 18. For independent approach to 1-epiaustraline (2), 12a was subjected to modification of functional groups with AcOAg after acetylation to afford an inseparable mixture of 24 and 25, from which tri TBS-protected 26 was derived through hydrolysis, hydogenolysis, and silylation.
