cuspareine and angustureine

Concise syntheses of the Hancock alkaloids (-)-angustureine and (-)-cuspareine are presented, applying and refining a recently developed rhodium-catalyzed hydroamination for the stereoselective construction of the chiral secondary amine. Furthermore, the syntheses include an allene synthesis via boron-magnesium exchange as well as the construction of the tetrahydroquinoline motive via a hydroboration/Suzuki-Miyaura coupling sequence.

Topics: Alkaloids; Amination; Amines; Catalysis; Molecular Structure; Quinolines; Rhodium

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

Topics: Alkaloids; Magnetic Resonance Spectroscopy; Molecular Structure; Quinolines

The antimalarial and toxicological properties of four tetrahydroquinoline alkaloids from Galipea officinalis trunk bark were studied. Crude extracts and pure alkaloids were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between compounds and the parasite culture, and ranged from 1.8 to 40 microg/ml for the chloroquine-sensitive strain (CQS) and from 0.09 to 38 microg/ml for the chloroquine-resistant strains (CQR). Galipinine yielded the best antimalarial effect (IC50: 0.09 - 0.9 microg/ml on CQR strain) and this compound interacted particularly between the 32(nd) and the 40(th) hour of the P. falciparum erythrocytic cycle. The cytotoxicity of the extracts and pure tetrahydroquinoline alkaloids was assessed on the HeLa cell line and showed IC50 values ranging from 5.8 to above 50 microg/ml.

Topics: Alkaloids; Animals; Antimalarials; Chloroquine; HeLa Cells; Humans; Plant Bark; Plant Extracts; Plasmodium falciparum; Quinolines; Rutaceae; Toxicity Tests; Venezuela