Asymmetric syntheses of (−)-isoretronecanol and (−)-trachelantamidine

Short and concise total asymmetric syntheses of (−)-isoretronecanol and (−)-trachelantamidine are reported. Oxidative cleavage of tert-butyl (S,S,S,Z)-7-[N-benzyl-N-(α-methylbenzyl)amino]cyclohept-3-ene-1-carboxylate, followed by hydrogenolysis promoted in situ cyclisation/reduction, which provided rapid access to the bicyclic core within (−)-isoretronecanol. Analogous treatment of the C(1)-epimer gave (−)-trachelantamidine. Overall, the syntheses of (−)-isoretronecanol and (−)-trachelantamidine were completed in eight and seven steps and 20 and 9.5% yield, respectively, from commercially available starting materials.

Graphical abstractShort and concise total asymmetric syntheses of (−)-isoretronecanol and (−)-trachelantamidine were completed in eight and seven steps and 20 and 9.5% overall yield, respectively, from commercially available starting materials, using the conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl (E)-hepta-2,6-dienoate and alkylation of the resultant β-amino enolate as the key stereodefining steps.Figure optionsDownload full-size imageDownload as PowerPoint slide