Synthesis of biologically active catecholic compounds via ortho-selective oxygenation of phenolic compounds using hypervalent iodine(V) reagents

A review. Catecholic motifs are present in numerous natural products and synthetic compds. used in various sectors of the chem. industries such as food, cosmetic, pharmaceutical and polymer industries. The antioxidant activity usually conferred to compds. bearing catecholic motifs is the property on which their application is often based. Although several (bio) chem. methods are available to chemists to produce catechols, the oxygenation of phenols constitutes one of the most practical approaches as long as the o-​selectivity of the process can be controlled. In this context, oxygenating hypervalent iodine(V) reagents offer a convenient metal-​free soln. Among these reagents, 2-​iodoxybenzoic acid (IBX) or its stabilized (non explosive) SIBX and polymer-​supported versions have found the most useful and successful applications in the conversion of phenols into o-​quinones, followed by redn. into catechols. Examples of oxygenative demethylation of 2-​methoxyphenols and o-​hydroxylation of phenolic compds. for the synthesis of biol. and industrially-​relevant catechols are highlighted in this review article, together with some mechanistic discussions on these transformations

Hypervalent iodine(III)-mediated oxidative acetoxylation of 2-methoxyphenols for regiocontrolled nitrogen benzannulation

Nitrogen-tethered 2-methoxyphenols are conveniently dearomatized into synthetically useful orthoquinol acetates by treatment with phenyliodine(III) diacetate in methylene chloride at low temperature. Subsequent fluoride- or base-induce intramolecular nucleophilic addition reactions furnish indole and quinoline derivatives. The potential of this methodology for the synthesis or a functionalized lycorine-type alkaloid skeleton is introduced here. (C) 2001 Elsevier Science Ltd. All rights reserved

Hypervalent iodine(III)-mediated oxidative acetoxylation of 2-methoxyphenols for regiocontrolled nitrogen benzannulation

Nitrogen-tethered 2-methoxyphenols are conveniently dearomatized into synthetically useful orthoquinol acetates by treatment with phenyliodine(III) diacetate in methylene chloride at low temperature. Subsequent fluoride- or base-induce intramolecular nucleophilic addition reactions furnish indole and quinoline derivatives. The potential of this methodology for the synthesis or a functionalized lycorine-type alkaloid skeleton is introduced here. (C) 2001 Elsevier Science Ltd. All rights reserved

Synthetic Studies toward C-Glucosidic Ellagitannins: A Biomimetic Total Synthesis of 5-O-Desgalloylepipunicacortein A

C-glucosidic ellagitannins constitute a subclass of bioactive polyphenolic natural products with strong antioxidant properties, as well as promising antitumoral and antiviral activities that are related to their capacity to interact with both functional and structural proteins. To date, most synthetic efforts toward ellagitannins have concerned glucopyranosic species. The development of a synthetic strategy to access C-glucosidic ellagitannins, whose characteristic structural feature includes an atropoisomeric hexahydroxydiphenoyl (HHDP) or a nonahydroxyterphenoyl (NHTP) unit that is linked to an open-chain glucose core by a C-aryl glucosidic bond, is described herein. The total synthesis of the biarylic HHDP-containing 5-O-desgalloylepipunicacortein A (1?beta) was achieved by either using the natural ellagic acid bis-lactone as a precursor of the requested HHDP unit or by implementing an atroposelective intramolecular oxidative biarylic coupling to forge this HHDP unit. Both routes converged in the penultimate step of this synthesis to enable a biomimetic formation of the key C-aryl glucosidic bond in the title compound

Synthesis of obovatol and related neolignan analogues as α-glucosidase and α-amylase inhibitors

: Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 μM; α-Glu: 248.3 μM) with IC5O value of 6.2-23.6 μM toward α-Amy and 39.8-124.6 μM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs

Synthesis of the pyoverdin chromophore by a biomimetic oxidative cyclization

The fluorescent dihydropyrimido[1,2-a]quinoline chromophore of the pyoverdin siderophores has been synthesized by a biomimetic oxidative cyclization using an iodine(III) reagent, followed by elimination and dehydrogenation