A highly stereoselective synthesis of novel cyclically constrained γ-amino acid residues is presented. The key step involves organocatalytic Michael addition of an aldehyde to 1-nitrocyclohexene. After aldehyde reduction, this approach provides optically active β-substituted-δ-nitro alcohols (96-99% e.e.), which can be converted to γ-amino acid amino acid residues with a variety of substituents at the α-position. We have used these new building blocks to prepare α/γ-peptide foldamers that adopt a specific helical conformation in solution and in the solid state.Oligomers constructed from β-amino acid residues ("β-peptides") or from combinations of α-and β-amino acid residues ("α/β-peptides") can adopt protein-like folding patterns. 1, 2 These conformational properties provide a basis for ongoing development of β-and α/β-peptides that display interesting functional properties. β-Amino acid residues can be endowed with higher intrinsic folding propensities than those of α residues by use of cyclic constraints to limit backbone torsional mobility, and this capacity for residue-based rigidification has proven to be important for both structure and function of β-and α/β-peptide foldamers.3 -6 Analogous benefits should result from the use of constrained γ-amino acid residues in foldamers, but it is difficult to explore this hypothesis because only a few types of ring-containing γ-amino acids are known. 7,8 The few cyclic γ residues examined to date have been found to promote sheet secondary structure,8b,c which contrasts with the helix-favoring effects of the most common cyclic β residues. 1,2,5,6 Here we report a new synthetic approach that provides γ-amino acids containing a cyclohexyl constraint on the C β -C γ bond and a variable side chain at C α . All three stereocenters of the γ-amino acid skeleton are generated from achiral precursors in a single process with high diastereo-and enantioselectivity. We show that the new type of γ-amino acid residue supports helix formation by an α/γ-peptide backbone. Figure 1 shows our synthetic approach, the key step of which is the pyrrolidine-catalyzed Michael addition of an aldehyde to 1-nitrocyclohexene. Chiral pyrrolidines have been shown to catalyze the Michael addition of aldehydes to nitroalkenes with high stereoselectivity. 9,10 Most precedents involve β-aryl nitroalkenes, such as β-nitrostyrene, which lead to γ 2,3 -amino acids.10a-d We have reported that Michael addition of aldehydes to nitroethylene provides access to γ 2 -amino acids. Our attention was drawn to 1-nitrocyclohexene as a Michael acceptor because the adducts could be easily converted to novel cyclically constrained γ-amino acid residues. Reaction of n-butanal and 1-nitrocyclohexene (2:1 molar ratio) in the presence of 20 mol % A in toluene provided only 25% of the Michael adduct after 24 hr, and the two major diastereomers (2a and 3a) were produced in a ~1:1 ratio (Table 1). When 10 mol % B was employed as a co-catalyst, the Michael adduct yield rose to 44% yield, and 2a was favored (6:1 dr)...

We propose that transesophageal echocardiography (TEE) can be used to guide cardiac arrest resuscitation. We undertook a literature search (Medline and EMBase) to assess articles on that topic. Our search yielded 55 articles falling into 3 categories: TEE used in operating rooms, TEE used in emergency departments, and TEE used in other settings. In many cases, TEE changed the direction of the resuscitation; however, it is unclear whether TEE changed patient‐oriented outcomes, such as neurologically intact survival. Few adverse events related to TEE have been documented. There is growing evidence that physicians can learn to use TEE during resuscitations and apply the findings to clinical decisions.

Emergency physicians (EP) frequently resuscitate and manage critically ill patients. Resuscitation of the crashing obese patient presents a unique challenge for even the most skilled physician. Changes in anatomy, metabolic demand, cardiopulmonary reserve, ventilation, circulation, and pharmacokinetics require special consideration. This article focuses on critical components in the resuscitation of the crashing obese patient in the emergency department, namely intubation, mechanical ventilation, circulatory resuscitation, and pharmacotherapy. To minimize morbidity and mortality, it is imperative that the EP be familiar with the pearls and pitfalls discussed within this article.

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