ajmaline and macroline

Topics: Ajmaline; Indole Alkaloids; Magnetic Resonance Spectroscopy; Molecular Structure; Oxindoles; Stereoisomerism; Tryptophan

Examination of the EtOH extract of the Malayan Alstonia penangiana resulted in the isolation of 10 new alkaloids, comprising two ajmaline (1, 2), four macroline oxindole (3-6), and four macroline-akuammiline bisindole alkaloids (7-10). The structures of these alkaloids were determined based on analysis of the spectroscopic data and, in the case of the oxindole 6 and the bisindole alkaloid 7, also confirmed by X-ray diffraction analysis. The bisindole alkaloids 7 and 8 showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, HCT 116, and A549 cells with IC

Topics: A549 Cells; Ajmaline; Alkaloids; Alstonia; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Crystallography, X-Ray; Cytotoxins; Drug Screening Assays, Antitumor; HCT116 Cells; HT29 Cells; Humans; KB Cells; MCF-7 Cells; Oxindoles; PC-3 Cells; Vincristine

A total of seventeen alkaloids, comprising six macroline (including alstofolinine A, a macroline indole incorporating a butyrolactone ring-E), two ajmaline, one sarpagine, and eight akuammiline alkaloids, were isolated from the stem-bark and leaf extracts of the Malayan Alstonia macrophylla. The structure and relative configurations of these alkaloids were established using NMR, MS and in several instances, confirmed by X-ray diffraction analysis. Six of these alkaloids were effective in reversing multidrug-resistance (MDR) in vincristine-resistant KB cells.

Topics: Ajmaline; Alstonia; Antineoplastic Agents, Phytogenic; Cell Proliferation; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indole Alkaloids; KB Cells; Models, Molecular; Molecular Structure; Oxindoles; Plant Leaves; Structure-Activity Relationship

A detailed account of the development of a general strategy for synthesis of the C-19 methyl-substituted alkaloids including total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1), 19(S),20(R)-dihydroperaksine (2), and peraksine (6) is presented. Efforts directed toward the total synthesis of macrosalhine chloride (5) are also reported. Important to success is the sequence of chemical reactions which include a critical haloboration reaction, regioselective hydroboration, and controlled oxidation (to provide sensitive enolizable aldehydes at C-20). In addition, the all-important Pd-catalyzed α-vinylation reaction has been extended to a chiral C-19 alkyl-substituted substrate for the first time. Synthesis of the advanced intermediate 64 completes an improved formal total synthesis of talcarpine (26) and provides a starting point for synthesis of macroline-related alkaloids 27-31. Similarly, extension of this synthetic strategy in the ring A oxygenated series should provide easy access to the northern hemisphere 32b of the bisindoles angustricraline, alstocraline, and foliacraline (Figure 4 ).

Topics: Ajmaline; Indole Alkaloids; Molecular Structure; Oxidation-Reduction; Oxindoles