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We report here the application of silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers synthetically valuable oxygenated cyclopentenone products in yields of ≤93% from both ketone- and aldehyde-derived silyl enol ethers, incorporates both terminal and internal alkyne partners, and delivers a variety of decorated systems, including more complex tricyclic structures. Facile removal of the silyl protecting group reveals oxygenated sites for potential further elaboration.

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.

Cells exposed to fast neutrons often exhibit a non-Poisson distribution of chromosome aberrations due to the high ionization density of the secondary reaction products. However, it is unknown whether lymphocytes exposed to californium-252 (252Cf) spectrum neutrons, of mean energy 2.1 MeV, demonstrate this same dispersion effect at low doses. Furthermore, there is no consensus regarding the relative biological effectiveness (RBE) of 252Cf neutrons. Dicentric and ring chromosome formations were assessed in human peripheral blood lymphocytes irradiated at doses of 12-135 mGy. The number of aberrations observed were tested for adherence to a Poisson distribution and the maximum low-dose relative biological effectiveness (RBEM) was also assessed. When 252Cf-irradiated lymphocytes were examined along with previously published cesium-137 (137Cs) data, RBEM values of 15.0 ± 2.2 and 25.7 ± 3.8 were found for the neutron-plus-photon and neutron-only dose components, respectively. Four of the five dose points were found to exhibit the expected, or close to the expected non-Poisson over-dispersion of aberrations. Thus, even at low doses of 252Cf fast neutrons, when sufficient lymphocyte nuclei are scored, chromosome aberration clustering can be observed.

Herein we target the total synthesis of 2-epi-α-cedren-3-one, a natural compound isolated from the essential oil of Juniperus thurifera. Overall, our synthetic sequence presents an optimised and robust series of chemical transformations, with prominent features including a low temperature and highly (Z)-selective Wittig olefination reaction, which is vital for the establishment of the relative stereochemistry within the final natural product, and a microwave-assisted, catalytic, intramolecular Pauson-Khand cyclisation reaction, which is used to construct the intriguing tricyclic core of the target molecule. Our optimum cyclisation protocol utilises only 20 mol% of transition metal, and delivers the complex tricyclic structure in just 10 min. Further manipulations of the annulation product culminate in the first total synthesis of the described natural target.

The initial discovery and establishment of a family of novel iridium catalysts possessing N-heterocyclic carbene units alongside bulky phosphine ligands allowed selected substrates to be labelled using deuterium or tritium gas at desirably low catalyst loadings via an ortho-directed C-H insertion process. Such a method has broad applicability and offers distinct advantages within the pharmaceutical industry, directly facilitating the ability to carefully monitor a potential drug molecule’s biological fate. Over the past decade since these initial protocols were divulged, many additional advances have been made in terms of catalyst design and substrate scope. This review describes the broadened array of new iridium catalysts and associated protocols for direct and selective C-H activation and hydrogen isotope insertion within a number of new chemical entities of direct relevance to the pharmaceutical industry.

The development of a sulfide-promoted, microwave-assisted Pauson-Khand reaction has enabled the formation of fused cyclopentenones using sub-stoichiometric quantities of a cobalt mediator over rapid reaction times and with no requirement for an external source of toxic carbon monoxide gas. This protocol displays applicability to both intra- and intermolecular Pauson-Khand reaction examples.

Health risks associated with the exposure of humans to low-dose ionizing radiation are currently estimated using the Linear-No-Threshold model. Over the last few decades, however, this model has been widely criticized for inconsistency with a large body of experimental evidence. Substantial efforts have been made to delineate biological mechanisms and health-related outcomes of low-dose radiation. These include a large DOE-funded Low Dose program operated in the 2000s, as well as the EU funded programs, previously NOTE and DOREMI and currently MELODI. Although not as widely known, the Atomic Energy of Canada Limited (AECL) in Chalk River, operated a low-dose radiobiology program since as early as 1948. The Canadian Nuclear Laboratories (CNL), the successor to AECL since 2015, has expanded this program into new areas making it the world's most robust, centrally coordinated and long-lived research efforts to delineate the biological effects of low-dose radiation. The purpose of this review is to provide a high-level overview of the low-dose radiobiology program maintained at CNL while capturing the historical perspectives. Past studies carried out at CNL have substantially influenced the area of low-dose radiobiology, exemplified by highly cited papers showing delays in spontaneous tumorigenesis in low-dose irradiated mice. The current low-dose research program at CNL is not only addressing a wide range of mechanistic questions about the biological effects of low doses - from genetic to epigenetic to immunological questions - but also moving toward novel areas, such as the dosimetry and health consequences of space radiation and the use of low-dose radiation in cancer therapy and regenerative medicine.

The A-D fragment of gambieric acids A and C has been synthesized using an asymmetric Tsuji-Trost allylation reaction to couple the two key segments. The A ring fragment has been prepared by a short and highly efficient route involving diastereoselective Lewis acid mediated alkylation of an acetal. Iterative ring-closing metathesis reactions have been used to construct cyclic ethers and assemble the tricyclic B-D fragment.

The use of alternative solvents in the iridium-catalysed hydrogen isotope exchange reaction with developing phosphine/NHC Ir(I) complexes has identified reaction media which are more widely applicable and industrially acceptable than the commonly employed chlorinated solvent, dichloromethane. Deuterium incorporation into a variety of substrates has proceeded to deliver high levels of labelling (and regioselectivity) in the presence of low catalyst loadings and over short reaction times. The preparative outputs have been complemented by DFT studies to explore ligand orientation, as well as solvent and substrate binding energies within the catalyst system.

The development of an iridium-catalyzed regio- and stereoselective dimerization process has enabled the formation of (Z)-enyne products. More specifically, low catalyst loadings of an iridium(I) complex, featuring a bulky N-heterocyclic carbene-phosphine ligand combination, has been successfully employed in this selective head-to-head dimerization of terminal alkynes via C-H activation.

Iridium(I) complexes of the type [(cod)Ir(NHC)(Py)]PF6 have been exposed as efficient catalysts in the area of hydrogen-isotope exchange. More specifically, by an ortho-directed C–H activation process, high levels of deuterium incorporation have been achieved using low levels of catalyst over a range of functionalised aromatic compounds. Additionally, the developed protocol has been extended to include a selected pharmacological target, where chemoselective labelling is observed within such a multifunctional substrate.

Biologically active α-methylenene propellanone has been synthesised in 12 steps in an overall yield of 11%. The key step of the synthesis, an intramolecular Pauson–Khand reaction, proceeds in good yield under alkyl sulfide promotion conditions, to furnish the 5,5-fused moiety within the target. Samarium diiodide-induced intramolecular conjugate addition onto the resulting cyclopentenone was used to complete the intriguing [3.3.3] propellanone skeleton.

Isotopic labelling is a key technology of increasing importance for the investigation of new CH activation and functionalization techniques, as well as in the construction of labelled molecules for use within both organic synthesis and drug discovery. Herein, we report for the first time selective iridium-catalyzed CH activation and hydrogen-isotope exchange at the β-position of unsaturated organic compounds. The use of our highly active [Ir(cod)(IMes)(PPh3 )][PF6 ] (cod=1,5-cyclooctadiene) catalyst, under mild reaction conditions, allows the regioselective β-activation and labelling of a range of α,β-unsaturated compounds with differing steric and electronic properties. This new process delivers high levels of isotope incorporation over short reaction times by using low levels of catalyst loading.

A preparatively accessible route to a series of conformationally-locked bicyclic morpholines has been developed. This flexible approach allows for diversification in order for a small array of lead-like scaffolds to be synthesised from readily available key building blocks.

The optimized conditions render possible the preparation of (Z)-enynes whose yield and selectivity depend on the substituents of the arene moiety.

The sayde Doctor Fian was soone after araigned, condemned, and adjudged by the law to die, and then to bee burned according to the lawe of that lande, provided in that behalfe. Whereupon hee was put into a carte, and beeing first strangle d, hee was immediatly put into a great fire, being readie provided for that purpose, and there burned in the Castle hill of Edenbrough on a Saterdaie in the ende of Januarie lastpast, 1591.1

The inside cover picture, by Kerr and co-workers depicts a series of robust, yet highly active Ir(I) complexes bearing specifically encumbered N-heterocyclic carbene and phosphine ligands. These complexes are extremely effective in hydrogen isotope exchange processes (with D or T), with low catalyst loadings, good levels of selectivity, and broad directing group applicability. The labelling of several complex drug molecules further highlights the catalysts’ utility. Mechanistic insight into the operation of these catalysts has also been provided by a combination of NMR and theoretical DFT studies.

Towards the synthesis of the novel natural product Agariblazeispirol C, (5aR*,11bR*)-9-methoxy-3,8,11b-trimethyl-5,6,7,11b-tetrahydro-1H-pentaleno[1,6a-a]naphthalen-4(2H)-one, C(20)H(24)O(2), has been prepared at a key stage of the preparative programme. The structure shows the desired stereochemical outcome of the central cyclization protocol, viz. a syn-relationship between the aliphatic methyl group on the 11b-position and the methylene group on the 5a-position [C-C-C-C = -34.57 (18) degrees ].

The addition of various nucleophiles to a vinyl 1,2,4-oxadiazole is described. Following optimisation, individual protocols tuned for the use of each specific class of reagent have been developed to allow the installation of nitrogen, sulfur, oxygen, and carbon nucleophiles, and leading to the preparation of a series of compounds containing the pharmaceutically important oxadiazole motif.