Activated Cyclopropanes: A Remarkable Breadth of Recent Chemistry

The reactions of cyclopropanes activated by electron-withdrawing groups and electron-donating groups – donor–acceptor (DA) cyclopropanes – and with alkenyl or alkylidene substituents has been an area of recent intense research activity. This Cluster contains contributions from many of the leading research groups in this area, and provides a concise introduction to the rich ring-opening, ring-expansion, dimerization, and cycloaddition chemistry of these compounds

Adding a structural context to the deprotometalation and trans-metal trapping chemistry of phenyl-substituted benzotriazole

Organometallic bases are becoming increasingly complex, because mixing components can lead to bases superior to single-component bases. To better understand this superiority, it is useful to study metalated intermediate structures prior to quenching. This study is on 1-phenyl-1H-benzotriazole, which was previously deprotonated by an in situ ZnCl2• TMEDA/LiTMP (TMEDA=N,N,N′,N′-tetramethylethylenediamine; TMP=2,2,6,6-tetramethylpiperidide) mixture and then iodinated. Herein, reaction with LiTMP exposes the deficiency of the single-component base as the crystalline product obtained was [{4-R-1-(2-lithiophenyl)-1H-benzotriazole• 3THF}2], [R=2-C6H4(Ph)NLi], in which ring opening of benzotriazole and N2 extrusion had occurred. Supporting lithiation by adding iBu2Al(TMP) induces trans-metal trapping, in which C-Li bonds transform into C-Al bonds to stabilise the metalated intermediate. X-ray diffraction studies revealed homodimeric [(4-R′-1-phenyl-1H-benzotriazole)2], [R′=(iBu)2Al(μ-TMP)Li], and its heterodimeric isomer [(4-R′-1-phenyl-1H-benzotriazole){2-R′-1-phenyl-1H-benzotriazole}], whose structure and slow conformational dynamics were probed by solution NMR spectroscopy

The effects of high-velocity hamstring muscle training on injury prevention in football players

Background: Explosive and fast body movements, sprints, jumps and quick changes of direction, which are characteristic of the football training, place considerable strain on the hamstring muscles. Due to the high occurrence of hamstring injuries, new preventive strategies are required that focus on high-velocity training. The purpose was to assess the effectiveness of high-velocity elastic-band training in reducing the occurrence of hamstring injuries in football players.Methods: Male football players from 15 teams (n = 319) playing in national competitions participated in this study. The players were involved in a 5-week exercise period in either the intervention group (INT) or the control group (CON), with a follow-up period of ∼4 months where hamstring injuries and exposure time were recorded. The INT group had two to three sessions per week of elastic-band training with low-load, high-velocity leg curls while lying prone; the CON group performed self-paced football-specific drills.Results: The incidence rate of hamstring injuries was 6.5% in the INT group (8 out of 123 players) and 9.2% in the CON group (18 out of 196 players). Although the INT group showed almost 1/3 reduction in hamstring injury incidence compared to the CON group, the difference was not statistically significant (p > 0.05). Moreover, no differences (p > 0.05, odds ratio [OR] = trivial-to-small) in distribution between the groups were found in hamstring injury characteristics (leg dominance and mechanism) except for the distribution of injuries that occurred during matches or training (p = 0.036; OR = 6.14, moderate).Conclusion: The program of high-velocity elastic-band training did not prove to be effective in preventing hamstring muscle injuries in football players despite displaying some positive indications that could be considering when creating injury prevention programs

Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Troger's Base: A Comparative Spectroscopic and Computational Study

The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2

Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis

Mycobacterium tuberculosis, the etiological agent of TB, possesses a cholesterol catabolic pathway implicated in pathogenesis. This pathway includes an iron-dependent extradiol dioxygenase, HsaC, that cleaves catechols. Immuno-compromised mice infected with a ΔhsaC mutant of M. tuberculosis H37Rv survived 50% longer than mice infected with the wild-type strain. In guinea pigs, the mutant disseminated more slowly to the spleen, persisted less successfully in the lung, and caused little pathology. These data establish that, while cholesterol metabolism by M. tuberculosis appears to be most important during the chronic stage of infection, it begins much earlier and may contribute to the pathogen's dissemination within the host. Purified HsaC efficiently cleaved the catecholic cholesterol metabolite, DHSA (3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione; kcat/Km = 14.4±0.5 µM−1 s−1), and was inactivated by a halogenated substrate analogue (partition coefficient<50). Remarkably, cholesterol caused loss of viability in the ΔhsaC mutant, consistent with catechol toxicity. Structures of HsaC:DHSA binary complexes at 2.1 Å revealed two catechol-binding modes: bidentate binding to the active site iron, as has been reported in similar enzymes, and, unexpectedly, monodentate binding. The position of the bicyclo-alkanone moiety of DHSA was very similar in the two binding modes, suggesting that this interaction is a determinant in the initial substrate-binding event. These data provide insights into the binding of catechols by extradiol dioxygenases and facilitate inhibitor design

Directed ortho -Metalation–Cross-Coupling Strategies. One-Pot Suzuki Reaction to Biaryl and Heterobiaryl Sulfonamides

International audienceA general synthesis of stable ortho-boropinacolato aryl and heteroaryl sulfonamides by directed ortho-metalation (DoM) and either MeOBPin or i-PrOBpin electrophile quench, 3 → 4, is described. A one-pot metalation–Suzuki cross-coupling procedure for the synthesis of biaryls and heterobiaryls, 3 → 5, and a complementary DoM–Ir-catalyzed boronation sequence (Scheme 6) are delineated