Synthesis of (+)-1-epiaustraline.
A highly efficient total synthesis of (+)-1-epiaustraline ((+)-1), a tetrahydroxypyrrolizidine alkaloid of the alexine/australine subclass, is described. The key step is a tandem intramolecular [4 + 2]/intermolecular [3 + 2] nitroalkene cycloaddition involving dienylsilyloxy nitroalkene 3 and chiral vinyl ether 4, which establishes four of the five stereocenters present. The final center was installed by a diastereoselective dihydroxylation. Hydrogenolytic unmasking of the nitroso acetal tosylate 17 containing the silyl ether linkage was thwarted by a slow alkylation and an undesired Peterson-type elimination. Prior removal of the silicon moiety by Tamao-Fleming oxidation proceeded in excellent yield and provided a substrate suitable for hydrogenolysis and deprotection. The complete synthesis required only 10 steps to deliver the (+)-1-epiaustraline in 7.0% overall yield.
Denmark
S E
SE
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA. denmark@scs.uiuc.edu
Cottell
J J
JJ
D006859:Hydrogen / Q000737:chemistry; D015394:Molecular Structure; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry
D011763:Pyrrolizidine Alkaloids; C412020:epiaustraline; D006859:Hydrogen