The dimeric pyrrole imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, high nitrogen content, and exciting bioactivities. This full account traces the evolution of a strategy that culminated in the first total syntheses of several members of this family, including sceptrin, ageliferin, nagelamide E, nakamuric acid (and its methyl ester), and oxysceptrin. Details on the fascinating conversion of sceptrin to ageliferin, which has been used to produce gram quantities of this sensitive natural product, are provided. In addition, the first enantioselective total synthesis of sceptrin and ageliferin are reported by programming the fragmentation of an oxaquadricyclane. A hallmark of our approach to this family of alkaloids is the minimal use of protecting groups despite the presence of 10 nitrogen atoms in the target compounds. Thus, the fundamental chemistry of the 2-aminoimidazole heterocycle was explored without masking its innate reactivity. Insights gained during these explorations led to total syntheses of oxysceptrin and nakamuric acid and a successful construction of the carbon skeleton of axinellamine.

Microwave‐induced magic: There is a widely held conviction that the antiviral marine alkaloid ageliferin 1 arises biosynthetically from a Diels–Alder reaction which, although possible, has yet to materialize in the laboratory. A total synthesis of 1 from sceptrin is now reported that has led to a new hypothesis for how 1 and other dimeric pyrrole‐imidazole alkaloids might be formed in nature.

Although biomimetic approaches have proven capable of converting resveratrol (1) concurrently into many of the more complex oligomers produced by plants throughout the world (such as 2-10), methods to access single members of the family have proven far more difficult to identify. Herein is described a strategy-level solution based on the use of a common building block, one distinct from Nature's starting material, that can participate in a variety of highly selective, reagent-controlled reaction cascades. These endeavors have led to the controlled synthesis of 25 natural products and analogues, molecules whose architectures encompass nearly all the carbogenic diversity of the resveratrol family.

Gifted with novel chemical features and extraordinary biological activity, sceptrin has remained a prominent unanswered synthetic challenge since its characterization in 1981 by Faulkner and Clardy. A concise and practical solution to the myriad of chemical challenges posed by sceptrin is reported in this Communication. Thus, through a sequence involving rearrangement of an oxaquadricyclane, a new method for chemo- and regioselective halogenation, a mild sequence for 2-aminoimidazole formation, and careful synthetic choreography, (+/-)-sceptrin is obtained in a minimum of steps and in 24% overall yield from dimethyl acetylenedicarboxylate without a single use of chromatography.

Despite the attention paid to resveratrol (1) owing to its potent biological activity, little effort has been devoted to studying resveratrol‐based oligomers (such as 2–4). The first general synthetic approach is outlined for accessing the carbogenic diversity possessed by this family of compounds.

Naturally radical: The microwave‐induced rearrangement of sceptrin to natural products ageliferin and nagelamide E results in approximately the same ratio as they are isolated from natural sources. Computational investigations show that the vinylcyclobutane–cyclohexene rearrangement occurs via diradical intermediates and support the involvement of this rearrangement in the biosynthesis of the natural products.

Covering: up to 2015Sesquiterpenoids are consistently attracting the interest of the scientific community due to their promising clinical profile as therapeutic agents. Cycloisomerization of enynes and dienes is a powerful tool in the hands of organic chemists to access them. In the last 20 years the field has witnessed remarkable advances, especially by revealing the capability of platinum and gold complexes to initiate such reactions. Nowadays, cycloisomerizations continue to enrich our knowledge with atom-economical routes and impressive cascades to reach more complex molecules. The current review covers the basic mechanistic aspects of metal catalysis in cycloisomerization reactions and their progress to the synthesis of selected complex sesquiterpenoids.

The CMS detector at the CERN LHC features a silicon pixel detector as its innermost subdetector. The original CMS pixel detector has been replaced with an upgraded pixel system (CMS Phase-1 pixel detector) in the extended year-end technical stop of the LHC in 2016/2017. The upgraded CMS pixel detector is designed to cope with the higher instantaneous luminosities that have been achieved by the LHC after the upgrades to the accelerator during the first long shutdown in 2013–2014. Compared to the original pixel detector, the upgraded detector has a better tracking performance and lower mass with four barrel layers and three endcap disks on each side to provide hit coverage up to an absolute value of pseudorapidity of 2.5. This paper describes the design and construction of the CMS Phase-1 pixel detector as well as its performance from commissioning to early operation in collision data-taking.