The Hancock alkaloids (-)-cuspareine, (-)-galipinine, (-)-galipeine, and (-)-angustureine: asymmetric syntheses and corrected 1H and 13C NMR data

Journal article

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-(α-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 1H and 13C 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.

Authors: Davies, S; Fletcher, A; Houlsby, I; Roberts, P; Thomson, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: Journal of Natural Products
• Volume: 81
• Issue: 12
• Pages: 2731–2742
• Publication date: 2018-11-20
• Acceptance date: 2018-11-20
• DOI: 10.1021/acs.jnatprod.8b00672
• EISSN: 1520-6025
• ISSN: 0163-3864
• Pmid: 30457859
• Language: English