Synthesis of polyhydroxylated pyrrolizidine alkaloids of the alexine family by tandem ring-closing metathesis-transannular cyclization. (+)-Australine.
Dienes 23 and 54, prepared from epoxy alcohol 9 via oxazolidinones 15 and 51, respectively, underwent ring-closing metathesis with Grubbs's catalyst to give azacyclooctenes 26 and 55. Treatment of each azacyclooctene with m-chloroperoxybenzoic acid afforded beta-epoxide 28 from 26 and alpha-epoxide 61 from 60. Basic hydrolysis of each of these oxazolidinones was accompanied by transannular attack at the epoxide by nitrogen, resulting in 2-(O-benzyl)-7-deoxyalexine (29) and 1,2-di-(O-benzyl)australine (62). The latter was converted to the alkaloid australine (3) upon hydrogenolysis. Attempts to effect ring-closing metathesis of dienes 37, 38, and 46 were unsuccessful, suggesting that, while one allylic oxygen substituent can be tolerated by Grubbs's catalyst, two cannot.
White
J D
JD
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA. james.white@orst.edu
Hrnciar
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D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007887:Fabaceae / Q000737:chemistry*; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010946:Plants, Medicinal; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D014197:Trees / Q000737:chemistry*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011763:Pyrrolizidine Alkaloids; C059794:australine; D005087:Glucan 1,4-alpha-Glucosidase