Noel F. Thomas

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.

Tandem pericyclic reactions in a new FeCl3-promoted synthesis of catechol analogues of restrytisol C

Abstract The uncommon stilbene, 3,4-dimethoxy-12-acetoxy stilbene, has been synthesised by Heck coupling methodology in three steps. Treatment of this stilbene with ferric chloride in dichloromethane (room temperature) gave the unnatural stilbenoid dimers; 8,8′-(12,12′-bisacetoxyphenyl)-7′-(3′,4′-dimethoxyphenyl)-3,4-dimethoxy-7′,8′-dihydro-naphthalene and 8-(12-acetoxyphenyl)-8′-(12′-hydroxy-phenyl)-7′-(3′,4′-dimethoxyphenyl)-3,4-dimethoxy-7′,8′-dihydro-naphthalene. The structures of both stilbene dimers were unambiguously confirmed by 1D ( 1 H, 13 C) and 2D NMR experiments (COSY, HMQC, HMBC and NOESY). This is the first report of a FeCl 3 -promoted sequential pericyclic pathway leading to a highly oxygenated oligostilbenoid dimer (incorporating two asymmetric centres). The NMR spectroscopic evidence and a mechanistic interpretation consistent with these structures are discussed.

Heimiol A, a new dimeric stilbenoid from Neobalanocarpus heimii

Abstract A new stilbene dimer, heimiol A was isolated from the heartwood of Neobalanocarpus heimii , in addition to the four known oligostilbenoids, balanocarpol, copalliferol A, hopeaphenol and vaticaphenol A. The structures and relative configuration were established by means of 2D NMR spectroscopy including COSY, HMQC, HMBC and NOESY.

Recent advances in the discovery and development of stilbenes and lactones in anticancer therapy

The stilbene and lactone moieties are important components of a number of compounds that have potential therapeutic roles in many areas including anticancer therapy. Since the significance of these moieties were recognised, a myriad of structurally-related or different analogues have been studied and tested against various pharmacological modalities that may provide novel targets in therapies, for example in conditions where insufficient apoptosis leads to the formation of cancer. Recently, there have been a number of studies directed at the search for novel anticancer compounds incorporating stilbene and/or lactone moieties. The particular aim of this review is to focus on, and summarise, selected patents from 1999 – 2003 on stilbenes and lactones with anticancer properties.

Synthesis, Characterization and Antifungal Evaluation of 5-Substituted-4-Amino-1,2,4-Triazole-3-Thioesters

A series of 5-substituted-4-amino-1,2,4-triazole-3-thioesters was synthesized by converting variously substituted organic acids successively into the corresponding esters, hydrazides, 5-substituted-1,3,4-oxadiazole-2-thiols, 5-substituted-1,2,4-triazole-2-thiols and 5-substituted-1,3,4-oxadiazole-2-thioesters. Finally the target compounds were obtained by refluxing 5-substituted-1,3,4-oxadiazole-2-thioesters in the presence of hydrazine hydrate and absolute alcohol. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.

Transformations of the 2,7-Seco Aspidosperma Alkaloid Leuconolam, Structure Revision of epi-Leuconolam, and Partial Syntheses of Leuconoxine and Leuconodines A and F.

Several transformations of the seco Aspidosperma alkaloid leuconolam were carried out. The based-induced reaction resulted in cyclization to yield two epimers, the major product corresponding to the optical antipode of a (+)-meloscine derivative. The structures and relative configuration of the products were confirmed by X-ray diffraction analysis. Reaction of leuconolam and epi-leuconolam with various acids, molecular bromine, and hydrogen gave results that indicated that the structure of the alkaloid, previously assigned as epi-leuconolam, was incorrect. This was confirmed by an X-ray diffraction analysis, which revealed that epi-leuconolam is in fact 6,7-dehydroleuconoxine. Short partial syntheses of the diazaspiro indole alkaloid leuconoxine and the new leuconoxine-type alkaloids leuconodines A and F were carried out.

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.

Cytotoxic Constituents from the Rhizomes of Curcuma zedoaria

Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.01,5]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1–19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 ± 1.0 and 9.3 ± 0.3 μg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer.

Perhentidines A−C: Macroline−Macroline Bisindoles from Alstonia and the Absolute Configuration of Perhentinine and Macralstonine

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.

Seco-tabersonine alkaloids from Tabernaemontana corymbosa

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.