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An experimental foray into the potential of oxazoles and thiazoles to enter into CpCo-mediated [2+2+2] cycloadditions is described. α,ω-Diynes failed to engage the heterocycles productively, as illustrated by the behavior of the unique cobaltacyclopentadiene(oxazole) complex 10 , the isolation and X-ray structural determination of which is recorded. Alkyne-tethered systems gave moderate yields to products resulting from [2+2+2] cycloaddition and C–H activation. The azaenol ether bridge in the cycloaddition products appears sensitive to oxidation, elimination, and rearrangement, depending on the system and reaction conditions.

The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided.

The immune system provides defense against tumors and pathogens. Here, we propose that by elucidating the shared principles of immunity that underlie cancer and infectious disease, oncologists and microbiologists can learn from each other and achieve the deeper mechanistic understanding critical the development of therapeutic approaches.

Radial (tetracyclopentadienyl)cyclobutadiene pentametals have been synthesized by the Pd-catalyzed coupling of cyclopentadienyltin or of (CpM)zinc reagents with (tetraiodocyclobutadiene)iron(tricabonyl). X-ray structural and NMR data reveal that, while these arrays are crowded, the substituents enjoy considerable rotational freedom. The method constitutes a significant complement to currently existing strategies for the construction of persubstituted cyclobutadiene complexes.

Irradiation (λmax = 300−375 nm) of FvRu2(CO)4 (1, Fv = η5:η5-bicyclopentadienyl) or (μ2-η1:η5-cyclopentadienyl)2Ru2(CO)4 (2) with dimethyl cis- or trans-butenedioate resulted in FvRu2(η2-trans-CHRCHR)(CO)3 (3, R = CO2CH3). Prolonged irradiation of 1−3 provided FvRu2(η2-trans-CHRCHR)2(CO)2 (4a, R = CO2CH3) and FvRu2(η2-cis-CHRCHR)(η2-trans-CHRCHR)(CO)2 (4b, R = CO2CH3). Photocatalytic isomerization of cis to trans alkene occurred in the presence of 1−4. Irradiation of 1−3 with dimethyl butynedioate produced FvRu2(μ2-η2-dimethyl butynedioate)(CO)3 (5). Prolonged irradiation of 1−5 with the alkyne afforded FvRu2(μ2-η2:η4-CRCRCRCR)2(CO) (6, R = CO2CH3). Irradiation of a THF solution of 6 generated FvRu2(μ2-η2:η4-CRCRCRCR)2(THF) (7, R = CO2CH3). Photochemical alkyne cyclotrimerization was observed in the presence of 1−7. In the presence of CO, 7 reverted to 6 thermally. Heating 7 in the presence of dimethyl cis-butenedioate, thiophene, PPh3, or dimethyl sulfoxide (DMSO) afforded FvRu2(μ2-η2:η4-CRCRCRCR)2(L) (8...

Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.

(Fulvalene)hexacarbonyldirhenium (1) furnishes the first silylene fulvalenedimetal complex 3 by double Si−H activation. The solid-state structure of the molecule was determined by X-ray analysis and its solution dynamics by 1H NMR spectroscopy.

A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.