Current Organic Chemistry - Volume 16, Issue 5, 2012

(Poly)phenols1 are, in my opinion, the most investigated family of natural products. Research into their occurrence, their (bio)organic (hemi)syntheses, their physicochemical properties, their biological effects so as their industrial use are indeed highly documented in the literature. Accordingly, (poly)phenols represent nowadays a very relevant family of natural products whose peculiarity clearly relies on its close connection to many fields of organic chemistry, ranging from phytochemistry (i.e., natural product chemistry), through physical, analytical and bio-organic chemistries, to organic synthesis. This unique multi-disciplinary feature of (poly)phenol chemistry is thus highlighted in the present Hot Topic Special Volume entitled ‘(POLY)PHENOL CHEMISTRY’ and consisting of two consecutive issues: (i) Part I - Organic Synthesis; (ii) Part II - Physicochemical Properties & Biological Implications. Gathering in-depth contributions of 9 experts in (poly)phenol chemistry from diverse (but interdependent!) chemical ‘horizons’, this Special Volume aims at exhibiting the undisputed importance of (poly)phenols to organic chemistry. The present issue, namely Part I - Organic Synthesis, contains 5 contributions of synthetic relevance, each contribution (the last one excepted) reviewing the current strategies and methods for the synthesis of a peculiar type of (poly)phenolic architectures. To the best of my knowledge, such an issue gathering together reviews related only to synthetic aspects of (poly)phenols is unprecedented in the literature. In this regard, this issue intends to make both specialists and non-specialists aware of the unique and wide chemical reactivity exhibited by the huge array of (poly)phenolic scaffolds elaborated by Mother Nature. First, Peter LANGER (Universitat Rostock, Rostock, Germany) et al. offer a mini-review summarizing the synthetic applications of an elegant [3+3] cyclocondensation-type approach for constructing highly functionalized phenols from acyclic (and thus non-aromatic!) precursors.....

As a young PhD I remember my first conscious contact with the multi-coloured anthocyanins a polyphenol subclass. It was downtown Paris at the Jardin des Plantes, the former Jardin du Roy. Its gardeners used to grow a lot of ornamental plants possessing a rich variety of flower colours. The scenery was so superb that I came to the decision to try to understand how plants generate all these fantastic colours. It was my first step towards polyphenol research. There is little doubt that polyphenols are among the most popular molecules as far as the general public is concerned. Nowadays, these natural or synthetic substances are almost always seen as good for your health wherever they come from. Probably the best sources are to be found in vegetables, fruits as well as in other parts of plants including tubers, grains, flowers and roots. Since most of the developed countries population is located in large cities or urban areas, few people of such countries have access to gardening. Therefore, to consume the recommended amounts of food containing polyphenols, they rely on supermarkets for edible parts of fresh plants or on drugstores for more or less concentrated extracts of all kind of vegetables supposed to prevent from diseases going from heart attacks to cancers. The magic word associated with polyphenols is anti-oxidant although, under certain conditions, a few of them seem to act as pro-oxidant! Oxidation has been definitively classified in the bad category of biochemical reactions. But, we human beings need a lot of oxygen our whole life long. Together oxygen and water can produce lots of oxidizing species and where there is life there is water. Therefore reactive oxygen species can reach living targets wherever they are. So, polyphenols are welcome since, being rich in exchangeable hydrogen atoms, it is usually assumed that they provide protection against oxidation damages. Ageing, if not exactly identical to oxidation, is frequently reported as the worst that can happen to a living species. It is thus easily conceivable the astonishing number of anti-oxidant pills taken by human bodies. One should add that the caloric balance of polyphenols is good, nothing to compare with the hated, but so delicious, structurally simple sugars! The structural diversity of phenolic compounds is extremely large. It is therefore not so surprising that synthetic strategies have accumulated over the years to provide pure compounds in good quantities. Indeed, pure polyphenols are not easily extracted from plants, even if starting materials can often be obtained in huge amounts. One should think of tea leaves, cocoa beans and grapes, for instance. In this special issue of Current Organic Chemistry, as scientific editor, Stefan Chassaing has gathered a panel of scientists who develop the more recent synthetic views to target polyphenolics with promising medicinal and biological properties. Polyphenols interactions with proteins, anti-oxidant activity of plant phenols and anthocyanin copigmentation, in relation to wine ageing, are also reviewed. All the authors are masters in their fields and the special issue has its very place in every laboratory investigating chemical and biochemical subjects related to polyphenols.

Formal [3+3] cyclocondensation reactions of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with functionalized and nonfunctionalized 1-alkyl- and 1-aryl-3-alkoxy-2-en-1-ones, 1,1-dichloro-3-buten-2-ones, 3-acyl-4,5-dihydrofurans and other related 1,3- dielectrophiles provide a convenient and regioselective approach to various highly substituted, functionalized phenols which are not readily available by other methods.

Oligomeric proanthocyanidins (OPAs) are components of a wide variety of plant-derived materials and foodstuffs and their well-known biological activities, especially with respect to their significance in human health, have generated a great deal of interest in the scientific community. This review summarizes synthetic approaches to OPAs.

Ellagitannins are a structurally and biologically diverse class of hydrolysable tannins. The structure typically consists of galloyl and hexahydroxydiphenoyl group(s), which are esterified to glucose. A number of biological and pharmacological activities have been reported in this class of natural products. The focus of this review is progress in strategies and methodologies for the total synthesis of ellagitannins. The first half of this review describes the previously achieved total syntheses along with the synthetic problems and solutions including formation of the HHDP-bridge, preparation of dehydrodigalloyl ether, control of anomeric isomers, and protecting groups in the syntheses. The latter half describes the three recent total syntheses of ellagitannins including details of the first synthesis of an axial- rich ellagitannin, of which glucose moiety is in a 1C4 or a twist-boat conformation that has more axially oriented C-O bonds.

This review covers synthetic work carried out in the field of stilbene and oligostilbene chemistry. It includes a brief overview of the methods used for the synthesis of monomeric stilbenoids. The production of oligomeric species by means of enzymatic or microbial conversion is examined in detail. Biomimetic syntheses of stilbene oligomers are then scrutinised. Most of the work is based on the dimerisation of stilbenoid monomers with help of one-electron oxidants or through acid catalysis. Mechanistic interpretations of the oxidative couplings observed by the various groups are proposed and suggest that the outcome of these reaction be guided by the “hard and soft acid and base” (HSAB) principle together with supramolecular interactions between the reacting stilbenoid monomers. Eventually, the few non-biomimetic full syntheses are presented and their strategies analysed.

This review covers recent advances in the synthetic labelling and biolabelling of dietary polyphenols over the last 10 years. During this period, the production of labelled flavans and their proanthocyanidin oligomers, isoflavones, lignans and stilbenes such as resveratrol, has received the most attention. Radiolabelled compounds are mostly used for tissue distribution and pharmacokinetic studies in animals. In parallel, methods for the synthesis of more easily handled compounds labelled with stable isotopes have been extensively developed. The use of both types of labelled compounds in metabolic studies has significantly contributed to the identification of metabolites produced by the intestine, the liver, and/or the colonic microflora.