Readily available biphenyl derivatives containing an alkyne unit at one of their ortho-positions are converted into substituted phenanthrenes on exposure to catalytic amounts of either PtCl2, AuCl, AuCl3, GaCl3 or InCl3 in toluene. This 6-endo-dig cyclization likely proceeds through initial pi-complexation of the alkyne unit followed by interception of the resulting eta2-metal species by the adjacent arene ring. The reaction is inherently modular, allowing for substantial structural variations and for the incorporation of substituents at any site of the phenanthrene product. Moreover, it is readily extended to the heterocyclic series as exemplified by the preparation of benzoindoles, benzocarbazoles, naphthothiophenes, as well as bridgehead nitrogen heterocycles such as pyrrolo[1,2-a]quinolines. Depending on the chosen catalyst, biaryls bearing halo-alkyne units can either be converted into the corresponding 10-halo-phenanthrenes or into the isomeric 9-halo-phenanthrenes; in the latter case, the concomitant 1,2-halide shift is best explained by assuming a metal vinylidene species as the reactive intermediate. The scope of this novel method for the preparation of polycyclic arenes is illustrated by the total synthesis of a series of polyoxygenated phenanthrenes that are close relatives of the anticancer agent combretastatin A-4, as well as by the total synthesis of the aporphine alkaloid O-methyl-dehydroisopiline and its naturally occurring symmetrical dimer.

Synthesis of Phenanthrenes and Polycyclic Heteroarenes by Transition‐Metal Catalyzed Cycloisomerization Reactions

Since the dawn of the 20th century, the average life expectancy at birth has nearly doubled due to advances in science and medicine. As medical records grew more reliable, it became apparent that, while overall life span was increasing, there were significant epidemiological differences between geographical regions, with people from countries such as Japan, France, and Switzerland enjoying longer life expectancy as compared to other regions of the world. The causative factors for these disparities in both mortality and morbidity have been attributed not only to genetics but also to the contributions of highly variable lifestyle and environmental influences.1 Barring differences in modernization and public health policy, diet is the most significant epidemiological factor cross-culturally and is thought to be a profoundly important contributor to health and overall well-being.

Prior to the early 1990s, there was a general consensus in support of the belief that moderate alcohol consumption significantly lowered the risk of coronary heart disease (CHD).2 However, it was not clear whether this was true of all alcoholic beverages or which constituents in the drinks were responsible for these beneficial properties.3 In 1992, Siemann and Creasy4 reported that resveratrol (1) was present in significant concentrations in red wine, drawing attention to the fact that it was also an active principle found in Japanese and Chinese folk medicines used to treat ailments related to the liver, skin, heart, and lipid metabolism.5 The discovery of resveratrol in wine was particularly timely; although the correlation between high fat and cholesterol consumption and coronary heart disease was widely accepted,6 certain populations, namely the French, had a low incidence of CHD mortality despite a diet and lifestyle that exposed these individuals to elevated risk factors.7 The cardioprotective ability of resveratrol, its oligomers, along with other phytochemicals present in wine, appeared to resolve this “French Paradox” and advanced the notion that a chemical constituent of one’s diet could be beneficial to health.8 Although the reality of the French Paradox remains contentious,9,10 research into the health benefits of resveratrol has exploded as a result. The reported biological activities of resveratrol are numerous, including antioxidant,11 anticancer,12 antidiabetic,13,14 cardioprotective,15 and even antiaging properties,16 to name a few. The body of literature regarding the biological activity of resveratrol is expansive and beyond of the scope of this review. We invite the readers to the following resources for background on this exciting and ongoing field of research.17−21

Despite its enormous popularity, resveratrol is but a single compound in a large, structurally diverse class of oligomeric stilbenoids that are present in the wines and foods that we consume.22,23 Until recently, access to these oligomeric natural products was limited to isolation from natural sources, which severely hampered their biological evaluation. The scientific interest in resveratrol has undoubtedly instigated the renewed attention in these compounds by the chemical community. Advances in the characterization, isolation techniques, and synthesis of these natural products have significantly enriched our understanding of their chemistry and biology. Our review seeks to document the history and recent progress in the isolation, chemical synthesis, and biology of this fascinating class of phytochemicals, while providing new insight on the biosynthesis and future prospects for the field as a whole.

Chemistry and Biology of Resveratrol-Derived Natural Products

The aim of this review is to summarize the various naturally occurring chalcone compounds which have been isolated from different plants. Chalcones considered as obligate intermediated in flavonoid biosynthesis but they do not accumulate to appreciable degree in most plants. The largest number of natural chalcones has been isolated from species of the Leguminosae, Asteraceae and Moraceae families. Chalcone accumulating plants have often been used in traditional medicine and chalcones have therefore been studied and reported to possess many beneficial biological effects including anti-inflammatory, antimicrobial, antifungal, antioxidant, cytotoxic, antitumor and chemopreventive activities. Previously published reviews on this topic survey the biological activities of natural and synthetic chalcones but there are no comprehensive contributions on occurrence and biological activities of natural chalcones. The present study provides an overview of hydroxy or/and methoxy-substituted chalcones, methylated, prenylated, geranylated and other monomeric derivatives, chromeno- and furanochalcones, dimeric chalcones and dihydrochalcone derivatives focusing on their biosynthesis, natural sources and biological activities. On the basis of 608 references, this review covers the phytochemistry and biological activity of natural chalcones, describing 646 compounds have been appeared in the literature since 1975. The summary is aimed to initiate further pharmacobotanical, biotechnological and medicinal studies on the field of chalcone research. This contribution reviews some of the general aspects of naturally occurring chalcones including their chemical categories, focusing on plant sources and biological activities. The review covers the major works appeared in the literature from 1975 up to 2014, relating to 608 references and 646 compounds.

Azizol A. Kadir

Papers

A dihydrochalcone from Lindera lucida

Sesquiterpenoids and diterpenoids from the liverwort Jungermannia truncata

Two 7,7′-bisdehydroaporphine alkaloids from Polyalthia bullata

Heimiol A, a new dimeric stilbenoid from Neobalanocarpus heimii

1-(2-hydroxy-3,4,5,6-tetramethoxyphenyl)-3-phenylpropene from Lindera lucida