sarpagine and macroline

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the

Topics: Antineoplastic Agents, Phytogenic; Apocynaceae; Indole Alkaloids; Molecular Structure; Oxindoles; Plant Extracts; Stereoisomerism; Vinblastine; Vincristine

Topics: Alstonia; Antineoplastic Agents, Phytogenic; Apoptosis; Drug Screening Assays, Antitumor; G1 Phase Cell Cycle Checkpoints; HT29 Cells; Humans; Indole Alkaloids; Mitochondria; Molecular Docking Simulation; Molecular Structure; Oxindoles; Tubulin Modulators

Fourteen previously undescribed alkaloids comprising two N-1-hydroxymethylmacroline alkaloids, one talpinine-type oxindole acetal, a pair of equilibrating talpinine-type oxindole hemiacetals, eight oxidized derivatives of sarpagine- and akuammiline-type indole alkaloids, in addition to alstochalotine a diastereomer of gelsochalotine recently isolated from Gelsemium elegans, were isolated from the leaf and stem-bark extracts of Alstonia penangiana. The structures and relative configurations of these alkaloids were established using NMR, MS, and in one instance, confirmed by X-ray diffraction analysis. An NMR-based method is described as a useful chemotaxonomic tool for differentiating between A. penangiana and A. macrophylla. Several of the alkaloids isolated showed appreciable growth inhibitory effects when tested against a number of human cancer cell lines.

Topics: Alkaloids; Alstonia; Humans; Indole Alkaloids; Molecular Structure; Oxindoles

A methanol extract of the stem bark of the Malayan

Topics: A549 Cells; Alkaloids; Alstonia; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Indole Alkaloids; Molecular Structure; Oxindoles

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

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 total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.

Topics: Alkaloids; Alstonia; Crystallography, X-Ray; Humans; Indole Alkaloids; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; Oxindoles; Plant Leaves; Vincristine

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

The aim of this study was to search for bioactive natural products from medicinal plants targeting vasorelaxant activity and we found the methanol extract from bark of Tabernaemontana dichotoma showed vasorelaxant activity on rat aorta. We isolated eight indole alkaloids including 10-methoxyalstonerine (1), a new macroline type indole alkaloid, from bark of T. dichotoma. These were respectively identified as 10-methoxyaffinisine (2), lochnerine (3), cathafoline (4), (-)-alstonerine (5), 19,20-dehydro-10-methoxytalcarpine (6), alstonisine (7), and alstonal (8) based on spectroscopic analysis. Among them, sarpagine type (2 and 3), akuammiline type (4), and macroline oxindole type (7 and 8) showed potent vasorelaxant activity. Mechanism of action on vasorelaxant activity of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) was clarified. Effects of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) were partially mediated the NO release from endothelial cells. Furthermore, 10-methoxyaffinisine (2) and alstonisine (7) attribute to the inhibitory effect of VDC and ROC, and cathafoline (4) have inhibitory effect on Ca(2+) influx via ROC. In addition, 10-methoxyaffinisine (2) as a major compound from bark of T. dichotoma showed hypotensive effect on normotensive rats in vivo.

Topics: Animals; Blood Pressure; Indole Alkaloids; Indoles; Male; Molecular Structure; Oxindoles; Rats; Rats, Wistar; Spiro Compounds; Tabernaemontana; Vasodilator Agents

Nine bisindole alkaloids, comprising four belonging to the macroline-sarpagine group, and five belonging to the macroline-pleiocarpamine group, were isolated from the stem-bark extracts of Alstonia angustifolia (Apocynacea). Their structures were established using NMR and MS analyses.

Topics: Alkaloids; Alstonia; Indole Alkaloids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Oxindoles

[reaction: see text] A palladium-catalyzed domino sequence was developed to rapidly construct the core structure of neosarpagine and other quinuclidine-related alkaloids. The cyclization of ketone 11 to ethylidene 4 with Pd(dba)2, DPEphos, LiHMDS, and ZnCl2 in THF represents a new domino process wherein a nonstabilized enolate served as a nucleophile.

Topics: Catalysis; Indole Alkaloids; Ketones; Models, Molecular; Molecular Structure; Oxindoles; Palladium; Quinuclidines