Jean Frédéric F. Weber

Regio‐ and Stereoselective Biomimetic Synthesis of Oligostilbenoid Dimers from Resveratrol Analogues: Influence of the Solvent, Oxidant, and Substitution

Oligostilbenoids are polyphenols that are widely distributed in nature with multifaceted biological activities. To achieve biomimetic synthesis of unnatural derivatives, we subjected three resveratrol analogues to oligomerization by means of one-electron oxidants. Upon varying the metal oxidant (AgOAc, CuBr(2), FeCl(3)6 H(2)O, FeCl(3)6 H(2)O/NaI, PbO(2), VOF(3)), the solvent (over the whole range of polarities), and the oxygenated substitution pattern of the starting material, stilbenoid oligomers with totally different carbon skeletons were obtained. Here we propose to explain the determinism of the type of skeleton produced with the aid of hard and soft acid/base concepts in conjunction with the solvating properties of the solvents and the preferred alignment by the effect of pi stacking.

Antioxidant properties of phenolic Schiff bases: Structure-activity relationship and mechanism of action

AbstractPhenolic Schiff bases are known for their diverse biological activities and ability to scavenge free radicals. To elucidate (1) the structure–antioxidant activity relationship of a series of thirty synthetic derivatives of 2-methoxybezohydrazide phenolic Schiff bases and (2) to determine the major mechanism involved in free radical scavenging, we used density functional theory calculations (B3P86/6-31+(d,p)) within polarizable continuum model. The results showed the importance of the bond dissociation enthalpies (BDEs) related to the first and second (BDEd) hydrogen atom transfer (intrinsic parameters) for rationalizing the antioxidant activity. In addition to the number of OH groups, the presence of a bromine substituent plays an interesting role in modulating the antioxidant activity. Theoretical thermodynamic and kinetic studies demonstrated that the free radical scavenging by these Schiff bases mainly proceeds through proton-coupled electron transfer rather than sequential proton loss electron transfer, the latter mechanism being only feasible at relatively high pH.

A new phytochemical survey of Malaysia. V: Preliminary screening and plant chemical studies

A large phytochemical survey of the flora of the Malaysian Peninsula and Sabah is described, covering the systematic search for alkaloids, and partly, for saponins and flavonoids. Details of some chemical studies are reported. This emphasizes the great interest of such a study.

Phytochemical and Cytotoxic Investigations of Curcuma mangga Rhizomes

Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), zerumin A (3), β-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.

Antimicrobial and cytotoxic activities of Malaysian endophytes

Endophytes, which are receiving increasing attention, have been found to be potential sources of bioactive metabolites following the discovery of paclitaxel producing endophytic fungi. In the present study, a total of 348 endophytes were isolated from different parts of 24 Malaysian medicinal plants. Three selected endophytes (HAB10R12, HAB11R3 and HAB21F25) were investigated for their antimicrobial and cytotoxic activities. For antimicrobial activity, HAB10R12 and HAB11R3 were found to be most active against bacteria and fungi, respectively. Their antimicrobial effects were comparable to, if not better than, a number of current commercial antibacterial and antifungal agents. Both HAB10R12 and HAB21F25 were found to be potential anticancer drug candidates, having potent activity against MCF‐7 and HCT116 cell lines and warrant further investigation. Copyright

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.

Antioxidant Activity of Hispidin Oligomers from Medicinal Fungi: A DFT Study

Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored mechanism involved in free radical scavenging, DFT calculations were carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The results showed that bond dissociation enthalpies of OH groups of hispidin oligomers (ArOH) and spin density delocalization of related radicals (ArO•) are the appropriate parameters to clarify the differences between the observed antioxidant activities for the four oligomers. The effect of the number of hydroxyl groups and presence of a catechol moiety conjugated to a double bond on the antioxidant activity were determined. Thermodynamic and kinetic studies showed that the PC-ET mechanism is the main mechanism involved in free radical scavenging. The spin density distribution over phenoxyl radicals allows a better understanding of the hispidin oligomers formation.

Manganese triacetate oxidative lactonisation of electron-rich stilbenes possessing catechol and resorcinol substitution (resveratrol analogues)

Abstract Treatment of 3,5-dimethoxy-12-benzyloxystilbene 10a or 3,4-dimethoxy-12-benzyloxystilbene 10b with Mn(OAc) 3 in acetic anhydride containing 13% acetic acid produced the lactones 4-(4′-benzyloxyphenyl)-5-(3′,5′-dimethoxyphenyl)-furan-2-one 11a and 4-(4-benzyloxyphenyl)-5-(3′,4′-dimethoxyphenyl)-furan-2-one 13 in yields of 35% as a 3:1 diastereomeric mixture (but as one regioisomer) and 13% as a mixture of regioisomers (1:1), respectively.

UV/Visible spectra of a series of natural and synthesised anthraquinones: experimental and quantum chemical approaches

Root decoctions of anthraquinone-containing plants are often taken as postpartum tonic and aphrodisiac. Anthraquinones are known for their diverse biological activities, especially antioxidant and anticancer. A series of 35 anthraquinones was generated by isolation from Rubiaceae plants and synthesis. Their UV/vis spectrum depends on the nature and relative positions of auxochromic substituents on the basic skeleton. To predict the maximum absorption bands for the current series of anthraquinones, excited sate calculations were performed using TD-DFT, CIS, ZINDO methods. The results showed that the use of PBE0 or its combination with B3LYP and B3P86 hybrid functionals are the most suitable to reproduce accurately the experimental λMAX. The structure–property relationships (SPRs) were established based on structural and electronic properties of the anthraquinones and showed (i) the importance of the number and position of OH groups and (ii) the positive contribution of the electrophilicity and hardness as electronic descriptors on position and amplitude of the maximum absorption bands.