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Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g. a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9‐azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9‐azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1‐azahomocubane. [ABSTRACT FROM AUTHOR]

D‐Ring‐seco‐limonoids (tetranortriterpenoids), such as gedunin and xylogranin B display anti‐cancer activity, acting via inhibition of Hsp90 and/or associated chaperon machinery (e.g. p23). Despite this, these natural products have received relatively little attention, both in terms of an enabling synthetic approach (which would allow access to derivatives), and as a consequence their structure–activity relationship (SAR). Disclosed herein is a generally applicable synthetic route to the BCD ring system of the seco‐D‐ring double bond containing limonoids. Furthermore, cell based assays revealed the first skeletal fragment that exhibited inhibition of the p23 enzyme at a level which was equipotent to that of gedunin, despite being much less structurally complex. The first synthetic route to the BCD ring system of the seco‐D‐ring limonoids has been devised. A synthetic intermediate displayed an equipotent p23 enzyme inhibitory effect to that of the more complex gedunin. [ABSTRACT FROM AUTHOR]

The Ley–Griffith oxidation, which is catalyzed by tetra‐n‐propylammonium perruthenate (TPAP, nPr4N[RuO4]), is a popular method for not only controlled oxidation of primary alcohols to aldehydes, but also a host of other synthetically useful transformations. While the fundamental reaction mechanism has recently been elucidated, several key hydrogen‐bonding interactions between the reagents were implicated but not investigated. Herein the prevalence of H‐bonding between the co‐oxidant N‐methylmorpholine N‐oxide (NMO), the alcohol substrate, water and the perruthenate catalyst is established. These observations help to rationalize the importance of drying the reagents and lead to several practical suggestions. Further exploration of the Ley–Griffith (TPAP) oxidation has unveiled a better understanding of the role N‐methylmorpholine N‐oxide (NMO) plays, not just as a co‐oxidant, but also a hydrogen bonding partner to the alcohol substrate and water. These additional attributes impact reaction performance, with important implications for the practicing synthetic chemist. [ABSTRACT FROM AUTHOR]

The Claisen rearrangement of benzylic substrates (benzyl vinyl ethers) has received considerably less attention than its well-known aliphatic and normal aromatic variants. Here, we review the rearrangement of both benzylic and heterobenzylic substrates, with examples of the reaction's use in the synthesis of natural products and drug-like molecules. [ABSTRACT FROM AUTHOR]

Claisen rearrangements of benzyl vinyl ethers are much less facile than those of aliphatic allyl vinyl ethers, and their synthetic utility has remained relatively unexplored. A one-pot procedure is reported for the generation and Claisen rearrangement of benzyl vinyl ethers that contain an activating α-alkoxy substituent on the vinyl group. A [3,3]-sigmatropic mechanism was supported by trapping of the intermediate isotoluene in an intramolecular Alder-ene reaction. [ABSTRACT FROM AUTHOR]

The Cover Feature shows the catalytic cycle of the Ley–Griffith oxidation, which like the site of the upcoming Heron8 conference on reactive intermediates and unusual molecules being held at Australia's iconic Uluru, works best under dry conditions. Extensive reaction monitoring has demonstrated that removal of product water by molecular sieves prevents sequestration of the co‐oxidant N‐methylmorpholine oxide (NMO) and decomposition of the tetrapro‐pylammonium perruthenate (TPAP) catalyst, leading to practical recommendations for synthetic chemists. Cover design by Kylie Agnew‐Francis. More information can be found in the Communication by P. V. Bernhardt, C. M. Williams et al. [ABSTRACT FROM AUTHOR]

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9-azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9-azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1-azahomocubane., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

D-Ring-seco-limonoids (tetranortriterpenoids), such as gedunin and xylogranin B display anti-cancer activity, acting via inhibition of Hsp90 and/or associated chaperon machinery (e.g., p23). Despite this, these natural products have received relatively little attention, both in terms of an enabling synthetic approach (which would allow access to derivatives), and as a consequence their structure-activity relationship (SAR). Disclosed herein is a generally applicable synthetic route to the BCD ring system of the seco-D-ring double bond containing limonoids. Furthermore, cell based assays revealed the first skeletal fragment that exhibited inhibition of the p23 enzyme at a level which was equipotent to that of gedunin, despite being much less structurally complex., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)