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DOI: 10.1055/s-0028-1083415
Synthesis of (+)-Nangustine
Contributor(s):Philip Kocienski, Indu DagerThe Australian National University, Canberra, Australia
Chemoenzymatic Approaches to the Montanine Alkaloids: A Total Synthesis of (+)-Nangustine
Tetrahedron 2008, 64: 6444-6451
Publication History
Publication Date:
23 October 2008 (online)
Key words
nangustine - Pictet-Spengler reaction - radical cyclization
Significance
(-)-Nangustine, a member of the montanine alkaloid family, is isolated from the bulbs of Narcissus angustifolius subsp. transcarpathicus. It shows selective activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Plasmodium falciparum. Other members of this family also show anxiolytic, antidepressive, anticonvulsive and hypotensive properties. A Pictet-Spengler reaction is used to introduce C6 and to assemble the 5,11-methanomorphanthridin-one framework in (+)-nangustine.
Comment
Enantiopure starting material, cis-1,2-dihydrocatechol A was obtained in multigram quantities by a whole cell-mediated biotransformation of chlorobenzene using a genetically engineered organism that overexpresses toluene dioxygenase. Treatment of acid chloride F with amine E under Schotten-Baumann conditions gave amide G as a 1:1 mixture of diastereoisomers, but after subjecting this diastereomeric mixture to radical addition-elimination (G → H) only a single diastereoisomer of lactam H was obtained.