The isoxazolidine ring represents one of the privileged structures in medicinal chemistry, and there have been an increasing number of studies on isoxazolidine and isoxazolidine-containing compounds. Optimization of the 1,3-dipolar cycloaddition (1,3-DC), original methods including electrophilic or palladium-mediated cyclization of unsaturated hydroxylamine, has been developed to obtain isoxazolidines. Novel reactions involving the isoxazolidine ring have been highlighted to accomplish total synthesis or to obtain bioactive compounds, one of the most significant examples being probably the thermic ring contraction applied to the total synthesis of (±)-Gelsemoxonine. The unique isoxazolidine scaffold also exhibits an impressive potential as a mimic of nucleosides, carbohydrates, PNA, amino acids, and steroid analogs. This review aims to be a comprehensive and general summary of the different isoxazolidine syntheses, their use as starting building blocks for the preparation of natural compounds, and their main biological activities.

IntroductionPre-hospital triage is a key element in a trauma system that aims to admit patients to the most suitable trauma center, and may decrease intra-hospital mortality. We evaluated the performance of a pre-hospital procedure in a regional trauma system through measurements of the quality of pre-hospital medical assessment and the efficacy of a triage protocol.MethodsOur regional trauma system included 13 hospitals categorized as Level I, II or III trauma centers according to their technical facilities. Each patient was graded A, B or C by an emergency physician, according to the seriousness of their injuries at presentation on scene. The triage was performed according to this grading and the categorization of centers. This study is a registry analysis of a three-year period (2009 to 2011).ResultsOf the 3,428 studied patients, 2,572 were graded using the pre-hospital grading system (Graded group). The pre-hospital gradation was closely related with injury severity score (ISS) and intra-hospital mortality rate. The triage protocol had a sensitivity of 92% (95% confidence interval (CI) 90% to 93%) and a specificity of 41% (95% CI 39% to 44%) to predict adequate admission of patients with ISS more than 15. A total of 856 patients were not graded at the scene (Non-graded group). Undertriage rate was significantly reduced in the Graded group compared with the Non-graded group, with a relative risk of 0.47 (95% CI 0.40 to 0.56) according to the definition of the American College of Surgeons Committee on Trauma (P <0.001). Where adjusted for trauma severity, the expected mortality rate at discharge from hospital was higher than observed mortality, with a difference of +2.0% (95% CI 1.4 to 2.6%; P <0.01).ConclusionsImplementation of a regional trauma system with a pre-hospital triage procedure was effective in detecting severe trauma patients and in lowering the rate of pre-hospital undertriage. A beneficial effect on outcome of such an organization is suggested.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0835-7) contains supplementary material, which is available to authorized users.

The conformational control of molecular scaffolds allows the display of functional groups in defined spatial arrangement. This is of considerable interest for developing fundamental and applied systems in both the fields of biology and material sciences. Peptides afford a large diversity of functional groups, and peptide synthetic routes are very attractive and accessible. However, most short peptides do not possess well-defined secondary structures. Herein, we developed a simple strategy for converting peptide sequences into structured γ-lactam-containing oligomers while keeping the amino acids side chain diversity. We showed the propensity of these molecules to adopt ribbon-like secondary structures. The periodic distribution of the functional groups on both sides of the ribbon plane is encoded by the initial peptide sequence.

Functional polymers, such as poly(ethylene glycol) (PEG), terminated with a single phosphonic acid, hereafter PEG ik-Ph are often applied to coat metal oxide surfaces during post-synthesis steps but are not sufficient to stabilize sub-10 nm particles in protein-rich biofluids. The instability is attributed to the weak binding affinity of post-grafted phosphonic acid groups, resulting in a gradual detachment of the polymers from the surface. Here, we assess these polymers as coating agents using an alternative route, namely, the one-step wet-chemical synthesis, where PEG ik-Ph is introduced with cerium precursors during the synthesis. Characterization of the coated cerium oxide nanoparticles (CNPs) indicates a core–shell structure, where the cores are 3 nm cerium oxide and the shell consists of functionalized PEG polymers in a brush configuration. Results show that CNPs coated with PEG1k-Ph and PEG2k-Ph are of potential interest for applications as nanomedicines due to their high Ce(III) content and increased colloidal stability in cell culture media. We further demonstrate that the CNPs in the presence of hydrogen peroxide show an additional absorbance band in the UV–vis spectrum, which is attributed to Ce–O2 2– peroxo-complexes and could be used in the evaluation of their catalytic activity for scavenging reactive oxygen species.

A stereoconservative three-step synthesis to access to 1,2,4-oxadiazine-3,6-dione is presented. This underexplored platform could be considered as a constrained oxy-azapeptide or an aza-diketomorpholine, the methodology being then successfully applied to produce enantiopure aza-analogs of diketomorpholine natural products. Importantly, the first crystal structures were obtained and compared to diketomorpholine and diketopiperazine structures. Finally, a straightforward procedure concerning the coupling of this heterocyclic scaffold with various amino acids to afford original pseudodipeptide analogs was described.

In actively bleeding trauma patients, meeting guideline criteria before considering rFVIIa was associated with lower mortality and a higher proportion of responders to the rFVIIa.

The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports.

Heavy silyl enol ethers (mostly TIPS and TBS) combine with cyclic N-alkenyl N-acyliminium salts generated in situ from their N,O-acetal precursors, to furnish highly functionalized indolizidines through an unprecedented double Mukaiyama-Mannich-Prins cascade transformation. This novel cascade annulation process demonstrates a promising scope, and takes place mostly catalytically with interesting stereocontrol. Furthermore, an appealing facet of this chemistry is emphasized with a bicatalytic approach by which the Mannich-Prins cascade follows a Ru-catalyzed N-allylamide to N-(E)-propenyl isomerization of the aminal counterpart in a one-pot operation.