A noncarbohydrate based approach to polyhydroxylated pyrrolidizines: total syntheses of the natural products hyacinthacine A1 and 1-epiaustraline.
[reaction: see text] A flexible route to polyhydroxylated pyrrolizidine alkaloids is described, starting from commercially available N-Boc pyrrole and using a partial reduction as the key step. Tactics for varying the stereochemistry around the ring by choice of partial reduction conditions are discussed and methods for constructing the bicyclic ring system of the pyrrolizidine targets are examined. Intramolecular S(N)2 type displacement reactions were found to be an efficient way of forming the requisite bicyclo ring systems while iodine-promoted cyclizations proved unsuitable. A first synthesis of hyacinthacine A1 is described that also confirmed the structure of the natural product, and a short stereoselective synthesis of 1-epiaustraline is also discussed in detail.
Donohoe
Timothy J
TJ
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom. timothy.donohoe@chem.ox.ac.uk
Sintim
Herman O
HO
Hollinshead
Jackie
J
D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011758:Pyrroles / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*; D013237:Stereoisomerism
D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; C412020:epiaustraline; C508850:hyacinthacine A1