Three new bisindole alkaloids, bisleuconothines B-D (1-3), were isolated from the bark of Leuconotis griffithii. Their structures were elucidated by 1D and 2D NMR spectroscopy and DFT calculations. Bisleuconothine B (1) is the first monoterpene indole alkaloid dimer featuring bridges between both C-16-C-10' and C-2-O-C-9'. All compounds were deemed noncytotoxic (IC50 > 10 μM) when tested against A549 human lung adenocarcinoma cells.
Racemic andransinine (1), an indole alkaloid derivative obtained during isolation of alkaloids from Alstonia angustiloba and Kopsia pauciflora, was found to undergo spontaneous resolution when crystallized in EtOAc, forming racemic conglomerates (an equimolar mechanical mixture of enantiomerically pure individual crystals). X-ray analyses of the enantiomers (obtained from crystals from EtOAc solution and from chiral-phase HPLC) provided the absolute configuration of each enantiomer as (15R,16S,21R)-(+)-andransinine (1a or I+) and (15S,16R,21S)-(-)-andransinine (1b or I-).
Three new bisindole alkaloids of the macroline-macroline type, perhentidines A-C (1-3), were isolated from the stem-bark extract of Alstonia macrophylla and Alstonia angustifolia. The structures of these alkaloids were established on the basis of NMR and MS analyses. The absolute configurations of perhentinine (4) and macralstonine (5) were established by X-ray diffraction analyses, which facilitated assignment of the configuration at C-20 in the regioisomeric bisindole alkaloids perhentidines A-C (1-3). A potentially useful method for the determination of the configuration at C-20 based on comparison of the NMR chemical shifts of the bisindoles and their acetate derivatives, in these and related bisindoles with similar constitution and branching of the monomeric units, is also presented.
Four new linearly fused bisindole alkaloids, lumutinines A-D (1-4), were isolated from the stem-bark extract of Alstonia macrophylla. Lumutinines A (1) and B (2) represent the first examples of linear, ring A/F-fused macroline-macroline-type bisindoles, while lumutinines C (3) and D (4) were constituted from the union of macroline and sarpagine moieties. A reinvestigation of the stereochemical assignment of alstoumerine (8) by NMR and X-ray diffraction analyses indicated that the configuration at C-16 and C-19 required revision.
Four tetracyclic oxindole alkaloids, 7(R)- and 7(S)-geissoschizol oxindole (1 and 2), 7(R),16(R)- and 7(S),16(R)-19(E)-isositsirikine oxindole (3 and 4), in addition to a taberpsychine derivative, N(4)-demethyltaberpsychine (5), were isolated from the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis.
The tryptamine-derived polycyclic bridged bioactive indole alkaloids subincanadines A-G were isolated in 2002 by Ohsaki and coworkers from the bark of the Brazilian medicinal plant Aspidosperma subincanum. Kobayashi proposed that subincanadines D-F could be biosynthetically resulting from stemmadenine via two different pathways and, furthermore, that the subincanadines A-C could be biogenetically resulting from subincanadines D and E. Kam and coworkers, in their focused efforts, isolated five indole alkaloids from Malaysian Kopsia arborea species, namely valparicine, apparicine, arboridinine, arborisidine, and arbornamine in combination with subincanadine E. On the basis of structural features, it has been proposed and proved in some examples that subincanadine E is a biogenetic precursor of these five different bioactive indole alkaloids bearing complex structural architectures. All important information on isolation, characterization, bioactivity, probable biogenetic pathways, and more specifically racemic and enantioselective total synthesis of subincanadine alkaloids and their biogenetic congeners are summarized in the present chapter. Special importance is given to the total synthesis and the synthetic strategies intended therein, comprising a set of main reactions.
Two new indole alkaloids characterized by previously unencountered natural product skeletons, viz., criofolinine (1), incorporating a pyrroloazepine motif within a pentacyclic ring system, and vernavosine (2, isolated as its ethyl ether derivative 3, which on hydrolysis regenerated the putative precursor alkaloid 2), incorporating a pyridopyrimidine moiety embedded within a pentacyclic carbon framework, were isolated from a Malayan Tabernaemontana species. The structures and absolute configuration of these alkaloids were determined on the basis of NMR and MS analysis and confirmed by X-ray diffraction analysis.
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.
A new indole alkaloid; neonaucline (1), along with six known compounds-Cadamine (2), naucledine (3), harmane, benzamide, cinnamide and blumenol A-were isolated from the leaves of Ochreinauclea maingayii (Rubiaceae). In addition to that of compound 1, (13)C-NMR data of cadamine (2) and naucledine (3) were also reported. Structural elucidations of these alkaloids were performed using spectroscopic methods especially 1D- and 2D-NMR, IR, UV and LCMS-IT-TOF. The excellent vasorelaxant activity on isolated rat aorta was observed for the alkaloids 1-3 after injection of each sample at 1 × 10(-5) M.
Seven new indole alkaloids of the Strychnos type, leuconicines A-G (1-7), and a new eburnan alkaloid, (-)-eburnamaline (8), were isolated from the stem-bark extract of two Malayan Leuconotis species. The structures of these alkaloids were established using NMR and MS analysis and in the case of 8 also by partial synthesis. Alkaloids 1-5 reversed multidrug resistance in vincristine-resistant KB cells.
A cytotoxic bisindole alkaloid possessing an unprecedented structure in which two indole moieties are bridged by an aromatic spacer unit has been isolated from Alstonia angustifolia. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway from pyrocatechuic acid and pleiocarpamine is presented.
Seven new indole alkaloids of the Aspidosperma type, jerantinines A-G (1-7), were isolated from a leaf extract of the Malayan Tabernaemontana corymbosa. The structures were established using NMR and MS analysis. Five of the alkaloids isolated and two derivatives (1-5, 8, 9) displayed pronounced in vitro cytotoxicity against human KB cells (IC50 < 1 microg/mL).
Two seco-tabersonine alkaloids, jerantiphyllines A and B, in addition to a tabersonine hydroxyindolenine, jerantinine H, and a recently reported vincamine alkaloid 7, were isolated from the leaf extract of the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis. Biomimetic conversion of jerantinines A and E to their respective vincamine and 16-epivincamine derivatives were also carried out.
Four bisindole alkaloids, viz., 19'(S)-hydroxyconodurine, conodurinine, 19'(S)-hydroxyconoduramine, and 19'(S)-hydroxyervahanine A, in addition to conodurine and ervahanine A, were obtained from the leaf and stem-bark extracts of Tabernaemontana corymbosa. The structures of the new alkaloids were determined using NMR and MS analysis.
Five new indole alkaloids of the ibogan type (1-5), in addition to 12 other known iboga alkaloids, were obtained from the leaf and stem-bark extract of the Malayan species Tabernaemontana corymbosa, viz., 19(S)-hydroxyibogamine (1), 19-epi-isovoacristine (2), isovoacryptine (3), 3R/S-ethoxyheyneanine (4), and 3R/S-ethoxy-19-epi-heyneanine (5). The structures were determined using NMR and MS analysis and comparison with known related compounds.
Ten new bisindole alkaloids of the vobasinyl-ibogan type, viz., conodiparines A-F (1-6), conodutarines A and B (7, 8), and cononitarines A and B (9, 10), were obtained from the leaf extract of the Malayan species Tabernaemontana corymbosa. The structures were determined using NMR and MS analysis.
Ten new indole alkaloids, alstomaline (1), 10,11-dimethoxynareline (2), alstohentine (3), alstomicine (4), 16-hydroxyalstonisine (5), 16-hydroxyalstonal (6), 16-hydroxy-N(4)-demethylalstophyllal oxindole (7), alstophyllal (8), 6-oxoalstophylline (9), and 6-oxoalstophyllal (10), in addition to 21 other known ones, were obtained from the leaf extract of the Malayan Alstonia macrophylla. The structures were determined using NMR and MS analysis.
Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
Two new bisindole alkaloids, leucophyllinines A (1) and B (2) consisting of eburnane and quebrachamine-type skeletons were isolated from the bark of Leuconotis eugeniifolia, and their structures were elucidated on the basis of spectroscopic data. Leucophyllinines A and B showed antiplasmodial activities against Plasmodium falciparum 3D7.
Two new indole alkaloids, neolamarckines A and B (1, 2) were isolated from the leaves of Neolamarckia cadamba (Rubiaceae). Structural elucidation of 1 and 2 was performed by combination of 2D-NMR and circular dichroism (CD) spectra, and chemical correlations. Neolamarckine A (1) showed inhibition of inducible nitric oxide synthase (iNOS) dose dependently.