Enantioselective formal total synthesis of the Dendrobatidae frog toxin, (+)-pumiliotoxin B, via O-directed alkyne free radical hydrostannation

Herein we describe our application of the O-directed free radical hydrostannation of disubstituted alkyl-acetylenes (with Ph3SnH and Et3B) to the (+)-pumiliotoxin B total synthesis problem. Specifically, we report on the use of this method in the synthesis of the Overman alkyne 8, and thereby demonstrate the great utility of this process in a complex natural product total synthesis setting for the very first time. We also report here on a new, stereocontrolled, and highly practical enantioselective pathway to Overman's pyrrolidine epoxide partner 9 for 8, which overcomes the previous requirement for use of preparative HPLC to separate the 1:1 mixture of diastereomeric epoxides that was obtained in the original synthesis of 9.

The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells. I

Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 mumol dm-3; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s-1 to 144 s-1, and for lethal lesion precursors from 533 s-1 to 165 s-1. This is generally consistent with the role of GSH in the repair-fixation model of radiation damage at the critical DNA lesions. However, the reduction in chemical repair rate was not proportional to the severe thiol depletion (down to almost-equal-to 1% for GSH) and a residual repair capacity remained (almost-equal-to 30%). This was found not to be due to compartmentalization of residual GSH in the nucleus, as the repair rate for dsb precursors in isolated nuclei, washed virtually free of GSH, was identical to that found in GSH-depleted cells (144 s-1), also the OER remained substantially above unity. This suggests that other reducing agents may have a role to play in the chemical repair of oxygen-dependent damage. One possible candidate is the significant level of protein sulphydryls present in isolated nuclei.

Free radical-mediated lipid peroxidation and systemic nitric oxide bioavailability:implications for postexercise hemodynamics

The metabolic vasodilator mediating postexercise hypotension (PEH) is poorly understood. Recent evidence suggests an exercise-induced reliance on pro-oxidant-stimulated vasodilation in normotensive young human subjects, but the role in the prehypertensive state is not known.

Asymmetric Total Synthesis of (+)-Inthomycin C Via O-Directed Free Radical Alkyne Hydrostannation with Ph3SnH and Catalytic Et3B: Reinstatement of the Zeeck-Taylor (3R)-Structure for (+)-Inthomycin C

A new pathway to (+)-inthomycin C is reported that exploits an O-directed free radical hydrostannation reaction on (−)-12 and a Stille cross-coupling as key steps. Significantly, the latter process was effected on 19 where a gauche-pentane repulsive interaction could interfere. Our stereochemical studies on the alkynol (−)-12 and the enyne (+)-7 confirm that Ryu and Hatakeyama’s (3S)-stereochemical revision of (+)-inthomycin C is invalid and that Zeeck and Taylor’s original (3R)-stereostructure for (+)-inthomycin C is correct.

Effects of antioxidant enzyme inhibitors on free radical levels in mice and possible clinical applications for decreasing ROS damage in the cochlea

This paper examines an experiment to determine if impairment of antioxident protective agents resulted in elevated ROS levels in mice.

Antioxidant and free radical scavenging activity of isoflavone metabolites

1. Soy isoflavones have been extensively studied because of their possible health-promoting effects. Genistein and daidzein, the major isoflavone aglycones, have received most attention; however, they undergo extensive metabolism in the gut and liver, which might affect their biological properties. 2. The antioxidant activity, free radical-scavenging properties and selected cellular effects of the isoflavone metabolites equol, 8-hydroxydaidzein, O-desmethylangiolensin, and 1,3,5 trihydroxybenzene were investigated in comparison with their parent aglycones, genistein and daidzein. 3. Electron spin resonance spectroscopy indicated that 8-hydroxydaidzein was the most potent scavenger of hydroxyl and superoxide anion radicals. Isoflavone metabolites also exhibited higher antioxidant activity than parent compounds in standard antioxidant (FRAP and TEAC) assays. However, for the suppression of nitric oxide production by activated macrophages, genistein showed the highest potency, followed by equol and daidzein. 4. The metabolism of isoflavones affects their free radical scavenging and antioxidant properties, and their cellular activity, but the effects are complex.

Antioxidant and free radical scavenging activity of isoflavone metabolites

1. Soy isoflavones have been extensively studied because of their possible health-promoting effects. Genistein and daidzein, the major isoflavone aglycones, have received most attention; however, they undergo extensive metabolism in the gut and liver, which might affect their biological properties. 2. The antioxidant activity, free radical-scavenging properties and selected cellular effects of the isoflavone metabolites equol, 8-hydroxydaidzein, O-desmethylangiolensin, and 1,3,5 trihydroxybenzene were investigated in comparison with their parent aglycones, genistein and daidzein. 3. Electron spin resonance spectroscopy indicated that 8-hydroxydaidzein was the most potent scavenger of hydroxyl and superoxide anion radicals. Isoflavone metabolites also exhibited higher antioxidant activity than parent compounds in standard antioxidant (FRAP and TEAC) assays. However, for the suppression of nitric oxide production by activated macrophages, genistein showed the highest potency, followed by equol and daidzein. 4. The metabolism of isoflavones affects their free radical scavenging and antioxidant properties, and their cellular activity, but the effects are complex.

Total phenolic content and free radical scavenging activities of methanolic extract powders of tropical fruit residues

Methanolic extract powders of acerola, passion fruit and pineapple industrial residues, including pulp, seeds and peel, altogether (except for acerola) devoid of seeds, were screened for antioxidant capacity. The total phenolic contents (TPCs) of the extract powders were compared with their radical-scavenging activities (RSA) against both DPPH(center dot) and superoxide anion (O(2)(center dot-)) radicals, and their protective effect against liposome peroxidation, triggered by peroxyl radical. Lipid peroxidation was followed by the fluorescence decay of the probe, 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C(11)-BODIPY(581/591)). The TPCs of acerola, passion fruit and pineapple extract powders were (94.6 +/- 7.4); (41.2 +/- 4.2) and (9.1 +/- 1.3) mg of gallic acid equivalents g(-1) of dry extract, respectively. Acerola showed the best RSA-DPPH(center dot) scores, whereas passion fruit was more protective on the RSA-O(2)(center dot-) system. Together with the protective effects against lipid peroxidation (rate of BODIPY decay) which, were similar for acerola and passion fruit extracts, these data suggest that the methanolic extracts of acerola and passion fruit residues may be useful as antioxidant supplements, particularly the acerola extract, due to its high phenolic content. (C) 2008 Elsevier Ltd. All rights reserved

Free radical scavenging profile and myeloperoxidase inhibition of extracts from antidiabetic plants: Bauhinia forficata and Cissus sicyoides

There is abundant evidence that reactive oxygen species are implicated in several physiological and pathological processes. To protect biological targets from oxidative damage. antioxidants must react with radicals and other reactive species faster than biological substrates do. The aim of the present study was to determine the in vitro antioxidant activity of aqueous extracts from leaves of Bauhinia forficata Link (Fabaceae - Caesalpinioideae) and Cissus sicyoides L. (Vitaceae) (two medicinal plants used popularly in the control of diabetes mellitus), using several different assay systems, namely, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) decolorization. superoxide anion radical (O-2 center dot-) scavenging and myeloperoxidase (MPO) activity. In the ABTS assay for total antioxidant activity, B. forficata showed IC50 8.00 +/- 0.07 mu g/mL, while C. sicyoides showed IC50 13.0 +/- 0.2 mu g/mL. However, the extract of C. sicyoides had a stronger effect on O-2 center dot- (IC50 60.0 +/- 2.3 mu p/mL) than the extract of B. forficata (IC50 90.0 +/- 4.4 mu g/mL). B. forficata also had a stronger inhibitory effect on MPO activity, as measured by guaiacol oxidation, than C. sicyoides. These results indicate that aqueous extracts of leaves of B. forficata and C. sicyoides are a potential source of natural antioxidants and may be helpful in the prevention of diabetic complications associated with oxidative stress.

Free radical scavenging activity of Pterogyne nitens Tul. (Fabaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Solvent free esterification reactions using Lewis acids in solid phase catalysis

A clean, efficient and fast method for esterification reactions for sterically (biodiesels) or otherwise inactive (aromatic) precursors was developed, using catalysts supported in a solid phase under solvent free conditions, and whose reactions can be promoted by MW irradiation. (c) 2006 Elsevier B.V. All rights reserved.