Warinthorn Chavasiri

Chemistry and Biology of the Caged Garcinia Xanthones

Natural products have been a great source of many small molecule drugs for various diseases. In spite of recent advances in biochemical engineering and fermentation technologies that allow us to explore microorganisms and the marine environment as alternative sources of drugs, more than 70 % of the current small molecule therapeutics derive their structures from plants used in traditional medicine. Natural-product-based drug discovery relies heavily on advances made in the sciences of biology and chemistry. Whereas biology aims to investigate the mode of action of a natural product, chemistry aims to overcome challenges related to its supply, bioactivity, and target selectivity. This review summarizes the explorations of the caged Garcinia xanthones, a family of plant metabolites that possess a unique chemical structure, potent bioactivities, and a promising pharmacology for drug design and development.

A limonoid from Xylocarpus granatum

A new limonoid, xyloccensin K, has been isolated from the seeds of Xylocarpus granatum, along with mixtures of steroids and long chain fatty acids and alcohols. X-ray crystallography has shown that xyloccensin K is similar to a number of previously reported limonoids, but that it contains a tetrahydrofuran sub-unit with oxygen bridging from C-3 to C-8.

Evaluation of the pharmacophoric motif of the caged Garcinia xanthones

The combination of unique structure and potent bioactivity exhibited by several family members of the caged Garcinia xanthones, led us to evaluate their pharmacophore. We have developed a Pd(0)-catalyzed method for the reverse prenylation of catechols that, together with a Claisen/Diels-Alder reaction cascade, provides rapid and efficient access to various caged analogues. Evaluation of the growth inhibitory activity of these compounds leads to the conclusion that the intact ABC ring system containing the C-ring caged structure is essential to the bioactivity. Studies with cluvenone (7) also showed that these compounds induce apoptosis and exhibit significant cytotoxicity in multidrug-resistant leukemia cells. As such, the caged Garcinia xanthone motif represents a new and potent pharmacophore.

Insect antifeedants, pterocarpans and pterocarpol, in heartwood of Pterocarpus macrocarpus Kruz.

The insect antifeedant activities of pterocarpans and a sesquiterpene alcohol from the dichloromethane extract of Pterocarpus macrocarpus Kruz. (Leguminosae) were evaluated against the common cutworm, Spodoptera litura F. (Noctuidae), and the subterranean termite, Reticulitermes speratus (Kolbe)(Rhinotermitidae). Three pterocarpans, (−)-homopterocarpin (1), (−)-pterocarpin (2), and (−)-hydroxyhomopterocarpin (3) and the sesquiterpene alcohol, (+)-pterocarpol (5), were isolated from the dichloromethane extract of the heartwood of P. macrocarpus under guidance by a biological assay. Among these natural products, the most active insect antifeedant against both S. litura and R. speratus was 1. On the other hand, sesquiterpene alcohol 5 showed less insect antifeedant activity than the other pterocarpans against both insect species. While its methylated derivative, (−)-methoxyhomopterocarpin (4), showed high biological activity, 3 showed less insect antifeedant activity in this study. Interestingly, racemic 1 did not show insect antifeedant activity against S. litura. However, all of the test pterocarpans and isoflavones showed antifeedant activity against the test termites. Additionally, since these compounds were major constituents of P. macrocarpus, these antifeedant phenolics may act as chemical defense factors in this tree. In Thailand, lumber made from this tree is used to make furniture and in building construction due to its resistance to termite attack.

Long chain aliphatic alcohols and saturated carboxylic acids from heartwood of Rhizophora apiculata

Abstract Five long chain aliphatic alcohols, 11 long chain aliphatic saturated carboxylic acids, three steroids, 2,6-dimethoxy-p-benzoquinone, syringaldehyde and sitosteryl 3-glucoside were isolated from the heartwood of Rhizophora apiculata and subsequently bioassayed for boll weevil antifeedant, antifungal and antimicrobial activity. While 2,6-dimethoxy-p-benzoquinone is the only constituent which exhibited activity, it is significant that this compound was active against fungi, bacteria and boll weevils.

New alkane functionalization reactions based on gif-type chemistry in the presence of alkali metal salts.

Abstract Cycloalkanes are transformed into monosubstituted cycloalkyl derivatives (chloride, azide, cyanide, thiocyanate, dicycloalkyl disulfide, or nitroalkane

Synthesis ofN-phenylphthalimide Derivatives as α-Glucosidase Inhibitors

SixteenN-phenylphthalimide derivatives were synthesized and their ability to inhibit α-glucosidase was investigated.N-(2,4-dinitrophenyl)phthalimide was a potent inhibitor of yeast α-glucosidase (IC50; 0.158 ± 0.005 mM) and maltase (IC50; 0.051 ± 0.008 mM), whereas it did not inhibit sucrase. From a Lineweaver-Burk plot of α-glucosidase kinetics,N-(2,4-dichlorophenyl) phthalimide was found to be a competitive inhibitor of yeast α-glucosidase. These results indicate thatN-(2,4-dinitrophenyl)phthalimide could be a representative of a new group of α-glucosidase inhibitors.

Coumarins from the heartwoods of Mansonia gagei Drumm.

Three coumarins and three known mansonones were isolated from the heartwood of Mansonia gagei Drumm. The structures of the three coumarins were elucidated as 3,8-dimethyl-5-isopropyl-6-methoxycoumarin (mansonrin A) 3,8-dimethyl-5-isopropyl-6-hydroxycoumarin (mansorin B) and 2,3-dihydro-3,6,9-trimethyl naphtho[1,8-bc]pyran-7-oxa-8-one (mansorin C) by analyses of physical properties and spectroscopic data. The cytotoxicity of the isolated compounds against brine shrimp Artemia salina Linn. was also evaluated.

A C-methylflavone from Trianthema portulacastrum

Abstract Extraction of Trianthema portulacastrum with dichloromethane has led to the isolation of a new flavonoid, 5,2′-dihydroxy-7-methoxy-6,8-dimethylflavone, along with 5,7-dihydroxy-6,8-dimethylchromone (leptorumol) which has been previously reported from a fern species. X-ray analysis of leptorumol is also reported.

Studies on the oxidation of alcohols employing t-butyl hydroperoxide (TBHP) and Fe(III) catalysts

Abstract New methodology for the oxidation of alcohols to ketones in good yield utilizing catalytic amounts of Fe III salts and TBHP as the oxidant is highlighted. Competition between alcohol and hydrocarbon oxidation has been clearly demonstrated. The “normal” Gif-type solvent system (pyridine / acetic acid) can be replaced by the alcohol itself.