Asymmetric synthesis of epicylindrospermopsin via intramolecular nitrone cycloaddition. Assignment of absolute configuration.
A synthesis of (-)-epicylindrospermopsin (2) was completed that establishes its absolute configuration and corroborates the corrected structural assignment previously made to this toxin by Weinreb et al. The hydroxylamine 3, prepared from 4-bromobenzyloxyacetaldehyde, was condensed with aldehyde 4, obtained in nine steps from (R)-methionine, to give nitrone 16. Intramolecular cycloaddition of 16 proceeded stereoselectively to yield the oxazabicyclo[2.2.1]heptane 17, which after reduction and deprotection afforded piperidine 18. The latter was transformed via cyclic urea 19 to the inverted C12 alcohol 20, and the derived azide 22 was cyclized to produce the guanidine moiety of 25. Final sulfation of the C12 hydroxyl group furnished (-)-2.
White
James D
JD
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331-4003, USA. james.white@orst.edu
Hansen
Joshua D
JD
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D001427:Bacterial Toxins; D000458:Cyanobacteria / Q000737:chemistry; D000087522:Cyanobacteria Toxins; D008968:Molecular Conformation; D009589:Nitrogen Oxides / Q000737:chemistry*; D013237:Stereoisomerism; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D000470:Alkaloids; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D009589:Nitrogen Oxides; C015388:nitrones; C089595:cylindrospermopsin; D014498:Uracil