Chew-Yan Gan

Grandilodines A−C, Biologically Active Indole Alkaloids from Kopsia grandifolia

Three new indole alkaloids (1-3), named grandilodines A-C, and five known ones were obtained from the Malayan Kopsia grandifolia. The structures were established using NMR and MS analyses and, in the case of 1 and 2, were confirmed by X-ray diffraction analyses. Alkaloids 1, 3, and lapidilectine B (8) were found to reverse multidrug resistance in vincristine-resistant KB cells.

Rhazinilam–Leuconolam–Leuconoxine Alkaloids from Leuconotis griffithii

Eight new indole alkaloids (1-8) belonging to the rhazinilam-leuconolam-leuconoxine group, in addition to 52 other alkaloids, were isolated from the stem-bark extract of Leuconotis griffithii, viz., nor-rhazinicine (1), 5,21-dihydrorhazinilam-N-oxide (2), 3,14-dehydroleuconolam (3), and leuconodines A-E (4-8). The structures of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 1, 5, and 7 showed only moderate to weak cytotoxicity toward KB cells (IC50 12-18 μg/mL), while 8 showed moderate activity in reversing MDR in vincristine-resistant KB cells.

Leuconicines A-G and (-)-eburnamaline, biologically active strychnan and eburnan alkaloids from Leuconotis.

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.

Leucoridines A−D, Cytotoxic Strychnos−Strychnos Bisindole Alkaloids from Leuconotis

Four new bisindole alkaloids of the Strychnos-Strychnos type, leucoridines A-D (1-4), were isolated from the stem-bark extract of Leuconotis griffithii. Alkaloids 1-4 showed moderate cytotoxicity against drug-sensitive and vincristine-resistant human KB cells.

Leucophyllidine, a Cytotoxic Bisindole Alkaloid Constituted From the Union of an Eburnan and a New Vinylquinoline Alkaloid

A cytotoxic bisindole alkaloid possessing an unprecedented structure constituted from the union of an eburnan half and a novel vinylquinoline alkaloid has been isolated from Leuconotis griffithii. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway to the novel quinolinic coupling partner is presented from an Aspidosperma precursor.

Voatinggine and tabertinggine, pentacyclic indole alkaloids derived from an iboga precursor via a common cleavamine-type intermediate

Two new indole alkaloids, voatinggine (1) and tabertinggine (2), which are characterized by previously unencountered natural product skeletons, were isolated from a Malayan Tabernaemontana species. The structures and absolute configuration of these alkaloids were determined using NMR and MS analysis, and X-ray diffraction analysis. A possible biogenetic pathway to these novel alkaloids from an iboga precursor, and via a common cleavamine-type intermediate, is presented.

Aspidospermatan-aspidospermatan and eburnane-sarpagine bisindole alkaloids from Leuconotis

Leucofoline and leuconoline, representing the first members of the aspidospermatan-aspidospermatan and eburnane-sarpagine subclasses of the bisindole alkaloids, respectively, were isolated from the Malayan Leuconotis griffithii. The structures of these bisindole alkaloids were established using NMR and MS analysis, and in the case of leuconoline, confirmed by X-ray diffraction analysis. Both alkaloids showed weak cytotoxicity towards human KB cells.

Criofolinine and vernavosine, new pentacyclic indole alkaloids incorporating pyrroloazepine and pyridopyrimidine moieties derived from a common yohimbine precursor

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.

Aspidofractinine and Eburnane Alkaloids from a North Borneo Kopsia. Ring-Contracted, Additional Ring-Fused, and Paucidactine-Type Aspidofractinine Alkaloids from K. pauciflora.

Eleven new indole alkaloids (1-11) comprising seven aspidofractinine and four eburnane alkaloids, were isolated from the stem-bark extract of Kopsia pauciflora occurring in Malaysian Borneo. The aspidofractinine alkaloids include a ring-contracted, an additional ring-fused, a paucidactine regioisomer, two paucidactine, and one kopsine alkaloid. The structures of several of these alkaloids were also confirmed by X-ray diffraction analyses. The bisindole alkaloids isolated, norpleiomutine and kopsoffinol, showed in vitro growth inhibitory activity against human PC-3, HCT-116, MCF-7, and A549 cells and moderate effects in reversing multidrug-resistance in vincristine-resistant human KB cells.

Corynanthean, eburnan, secoleuconoxine, and pauciflorine alkaloids from Kopsia pauciflora

Eleven indole alkaloids, comprising four corynanthean, two eburnane, one aspidofractinine, one secoleuconoxine, one andranginine, and two pauciflorine type alkaloids were isolated from the stem-bark and leaf extracts of Kopsia pauciflora. Their structures were determined using NMR and MS analyses. The catharinensine type alkaloid kopsirensine B and the secoleuconoxine alkaloid arboloscine A showed moderate to weak activity in reversing MDR in vincristine-resistant KB cells. The alkaloid content was markedly different compared to that of a sample from Malaysian Borneo.