Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Exactly half a century has passed since the launch of the first documented research project (1965 Dendral) on computer-assisted organic synthesis. Many more programs were created in the 1970s and 1980s but the enthusiasm of these pioneering days had largely dissipated by the 2000s, and the challenge of teaching the computer how to plan organic syntheses earned itself the reputation of a "mission impossible". This is quite curious given that, in the meantime, computers have "learned" many other skills that had been considered exclusive domains of human intellect and creativity-for example, machines can nowadays play chess better than human world champions and they can compose classical music pleasant to the human ear. Although there have been no similar feats in organic synthesis, this Review argues that to concede defeat would be premature. Indeed, bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules (with full stereo- and regiochemistry) coded in appropriate formats, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes. The Review begins with an overview of some basic theoretical concepts essential for the big-data analysis of chemical syntheses. It progresses to the problem of optimizing pathways involving known reactions. It culminates with discussion of algorithms that allow for a completely de novo and fully automated design of syntheses leading to relatively complex targets, including those that have not been made before. Of course, there are still things to be improved, but computers are finally becoming relevant and helpful to the practice of organic-synthetic planning. Paraphrasing Churchill's famous words after the Allies' first major victory over the Axis forces in Africa, it is not the end, it is not even the beginning of the end, but it is the end of the beginning for the computer-assisted synthesis planning. The machine is here to stay.

Computer-Assisted Synthetic Planning: The End of the Beginning.

https://pubs.rsc.org/en/Content/ArticlePDF/2016/NP/C6NP00021E

Recent advances in research on lignans and neolignans

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

Natural products as multidrug resistance modulators in cancer.

Three new indole alkaloids (1−3), named grandilodines A−C, and five known ones were obtained from the Malayan Kopsia grandifolia. The structures were established using NMR and MS analyses and, in the case of 1 and 2, were confirmed by X-ray diffraction analyses. Alkaloids 1, 3, and lapidilectine B (8) were found to reverse multidrug resistance in vincristine-resistant KB cells.

Grandilodines A−C, Biologically Active Indole Alkaloids from Kopsia grandifolia

A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.

Oxidized derivatives of macroline, sarpagine, and pleiocarpamine alkaloids from Alstonia angustifolia.

Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla

Eight new indole alkaloids (1–8) belonging to the rhazinilam–leuconolam–leuconoxine group, in addition to 52 other alkaloids, were isolated from the stem-bark extract of Leuconotis griffithii, viz, nor-rhazinicine (1), 5,21-dihydrorhazinilam-N-oxide (2), 3,14-dehydroleuconolam (3), and leuconodines A–E (4–8) The structures of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses Alkaloids 1, 5, and 7 showed only moderate to weak cytotoxicity toward KB cells (IC50 12–18 μg/mL), while 8 showed moderate activity in reversing MDR in vincristine-resistant KB cells

Yun-Yee Low

Papers

Grandilodines A−C, Biologically Active Indole Alkaloids from Kopsia grandifolia

Oxidized derivatives of macroline, sarpagine, and pleiocarpamine alkaloids from Alstonia angustifolia.

Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla

Rhazinilam-Leuconolam-Leuconoxine Alkaloids from Leuconotis griffithii.

Biomimetic oxidative transformations of pericine: partial synthesis of apparicine and valparicine, a new pentacyclic indole alkaloid from Kopsia