Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Evaluation of 1,1-cyclopropylidene as a thioether isostere in the 4-thio-thienopyrimidine (TTP) series of antimalarials.

The 4-(heteroarylthio)thieno[2,3-d]pyrimidine (TTP) series of antimalarials, represented by 1 and 17, potently inhibit proliferation of the 3D7 strain of P. falciparum (EC50 70-100 nM), but suffer from oxidative metabolism. The 1,1-cyclopropylidene isosteres 6 and 16 were designed to obviate this drawback. They were prepared by a short route that features a combined Peterson methylenation / cyclopropanation transformation of, e. g., ketone 7. Isosteres 6 and 16 possess significantly attenuated antimalarial potency relative to parents 1 and 17. This outcome can be rationalized based on the increased out-of-plane steric demands of the latter two. In support of this hypothesis, the relatively flat ketone 7 retains some of the potency of 1, even though it appears to be a comparatively inferior mimic with respect to electronics and bond lengths and angles. We also demonstrate crystallographically and computationally an apparent increase in the strength of the intramolecular sulfur hole interaction of 1 upon protonation.

Blunt abdominal aortic injury.

BACKGROUND: Blunt abdominal aortic injury (BAAI) is a rare injury with less than 200 cases in the current reported world literature, mostly in case report format. We sought to describe the experience of a high-volume trauma center and to provide a contemporary review of the literature to better understand the natural history and management of this injury. METHODS: This was a retrospective review of patients with BAAI between 1996 and 2010. Data collected included demographics, mechanism of injury, associated injuries, type of intervention, subsequent imaging, and follow-up. BAAI was classified by the presence of external aortic contour abnormality noted as an intimal tear, large intimal flap, pseudoaneurysm, or free rupture. Abdominal aorta zones of injury were classified by possible surgical approaches as zone I (diaphragmatic hiatus to superior mesenteric artery [SMA]), zone II (includes SMA and renal arteries), and zone III (from the inferior aspect of the renal arteries to the aortic bifurcation). RESULTS: We identified 28 individuals (68% male) with BAAI (median age, 28.5; range, 6-61 years). The median injury severity score was 45 (range, 16-75), and 39% were hypotensive at presentation. BAAI presented as intimal tear (21%), large intimal flap (39%), pseudoaneurysm (11%), and free rupture (29%). Zone III was the most common location of injury. Management depended on the location and type of injury: nonoperative (32%), open aortic repair (36%), endovascular repair (21%), and multimodality (10%). Overall mortality was 32%. Most deaths occurred during the initial operative exploration. The mortality rate of free aortic rupture was 100%. Intimal tears resolved or remained stable. Median follow-up was 15.5 months (range, 8 days-7.5 years). Vascular complications due to repair included a thrombosed access femoral artery during an endovascular repair and death of a patient who underwent a hybrid repair. CONCLUSIONS: This is the largest BAAI series described in the English literature at one institution. BAAIs range from intimal tears to free rupture, with outcomes and management correlating with type and location of injury. Nonoperative management with blood pressure control using ß-blockers coupled with antiplatelet therapy and close follow-up is successful in individuals with intimal tears with minimal thrombus formation because they remain stable or resolve on follow-up. Free rupture remains a devastating injury, with 100% mortality. For all other categories of aortic injury, successful repair correlates with a favorable prognosis.

Direct and indirect measures of verbal relational memory following anterior temporal lobectomy.

Medial temporal lobe (MTL) structures are implicated in forming conjunctions between events in order to form enduring relational memories; these memories are not evident using direct measures with varieties of amnesic subjects. Extratemporal brain structures are thought to be responsible for preserved memories, which are sometimes detectable using indirect measures. The present study tests this theory of multiple memory systems by examining whether preserved learning can be demonstrated for relational material in MTL-disordered subjects using an indirect measure which minimises conscious mediation of performance. The subjects had undergone anterior temporal lobectomy for relief of temporal lobe epilepsy: left-sided (LATL) cases had a mild verbal amnesia and right-sided (RATL) cases had better verbal memory, forming a comparison group. A direct measure of verbal relational memory was provided by successive trials of cued recall in a specially-constructed paired associate learning task with arbitrarily paired words; pairs consisted of either concrete or abstract words. LATL subjects performed worse than RATL subjects, and particularly so with abstract words. Following direct testing, memory for the pairings was measured indirectly using a masked recognition priming technique. RATL subjects showed savings in RT, demonstrating that masked priming can reveal evidence of the formation of conjunctions. Critically, LATL subjects showed no evidence of preserved learning with priming. Thus when MTL structures are damaged, relational memory appears to be affected without exception, consistent with the tenets of multiple memory systems theory.