The Hancock Alkaloids (-)-Cuspareine, (-)-Galipinine, (-)-Galipeine, and (-)-Angustureine: Asymmetric Syntheses and Corrected 1H and 13C NMR Data

The asymmetric syntheses of all members of the Hancock alkaloid family based upon a 2-substituted N-methyl-1,2,3,4-tetrahydroquinoline core are delineated. The conjugate addition of enantiopure lithium N-benzyl-N-(alpha-methyl-p-methoxybenzyl)amide to 5-(o-bromophenyl)-N-methoxy-N-methylpent-2-enamide is used to generate the requisite C-2 stereogenic center of the targets, while an intramolecular Buchwald-Hartwig coupling is used to form the 1,2,3,4-tetrahydroquinoline ring. Late-stage diversification completes construction of the C-2 side chains. Thus, (-)-cuspareine, (-)-galipinine, (-)-galipeine, and (-)-angustureine were prepared in overall yields of 30%, 28%, 15%, and 39%, respectively, in nine steps from commercially available 3-(o-bromophenyl)propanoic acid in all cases. Unambiguously corrected H-1 and C-13 NMR data for the originally isolated samples of (-)-cuspareine, (-)-galipinine, and (-)-angustureine are also reported, representing a valuable reference resource for these popular synthetic targets.