Practical asymmetric synthesis of a gamma-secretase inhibitor exploiting substrate-controlled intramolecular nitrile oxide-olefin cycloaddition

A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with > or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.     

Thermal destruction of spin-polaron bands in the narrow-gap correlated semiconductors FeGa3 and FeSb2

We report muon spin rotation spectra in the narrow-gap semiconductors FeGa(3) and FeSb(2) consistent with a narrow band of small spin polarons (SPs). The characteristic sizes obtained for these SPs are R(FeGa(3)) ≈ 0.3-0.6 nm and R(FeSb (2)) ≈ 0.3 nm, respectively. Such SP states are expected to originate from the exchange correlations between localized and itinerant electrons. Our data suggest that SP bands are formed at low temperature, but are destroyed by thermal fluctuations above 10 K in FeGa(3) and above 7 K in FeSb(2). Formation of such SP band states can explain many of the low-temperature properties of these materials.     

7,7‐Di­chloro‐1,6‐di­methyl‐2‐oxa‐5‐thia­bi­cyclo­[4.1.0]­heptane 5,5‐dioxide and 6‐chloro‐2,3‐di­hydro‐7‐methyl‐5‐methyl­ene‐2H,3H,5H‐1,4‐dithiepine 1,1,4,4‐tetraoxide

The structures of a 2‐oxa‐5‐thia­bi­cyclo­[4.1.0]­heptane derivative, C₇H₁₀Cl₂O₃S, (I), and a 2H,3H,5H‐1,4‐dithiepine derivative, C₇H₉ClO₄S₂, (II), are reported. The six‐membered ring in (I) has an envelope conformation and the seven‐membered ring in (II) adopts a chair conformation. There are no untoward intermolecular interactions in (I), but two Cl atoms make a short intermolecular contact across an inversion centre in (II), with a Cl?Cl distance of 3.2784 (9) Å, some 0.22 Å less than the sum of the van der Waals radii.     

Advantages and Limitations of Solid Layer Experiments in Muon Catalyzed Fusion

Since the discovery that muonic deuterium at energies near a few eV could travel distances of the order of 1 mm in condensed hydrogen, and in particular that muonic tritium and muonic deuterium could emerge from the surface of a solid hydrogen layer, the advantages of solid targets have enabled the study of several processes important in muon catalyzed fusion. A review of the results is presented, emphasizing the strengths and limitations of the use of solid hydrogen layer targets. This revised version was published online in August 2006 with corrections to the Cover Date.     

Experiments on the Magnetism of Sc Implanted into Metals

The study of dilute Sc impurities in either heavier d-transition metals or in alkali metal hosts is difficult due to their limited solubility; however, the large host-impurity mismatch in these systems makes them particularly interesting in terms of local electronic structure. One way to overcome the solubility problem is implantation into the desired host; in particular, using recoil implantation following heavy-ion nuclear reactions, deep implantation into practically any host can be achieved. Here, we compare the implantation of ⁴³Sc into Cs, studied in situ by the in-beam TDPAD method [1], with the implantation of ^44m Sc into Fe, studied by low-temperature nuclear orientation (LTNO) and related techniques (NMRON, thermal cycling) [2].     

Static and dynamic hyperfine interactions of Mn and Co impurities in the weak ferromagnet ZrZn2

We report the nuclear orientation of near-stoichiometric samples of ZrZn₂ containing trace impurities of radioactive⁵⁴Mn and⁶⁰Co in the temperature range 6.5–60 mK and in applied fields between 0.2 and 5.7 T. Analysis of the resullts indicates that in both cases, the transition-element impurities occupy two sites (the Zr and Zn sites) with about equal probablities. In one site, most probably that of Zr, both impurities have positive hyperfine fields of +12.0 T and +3.8 T for Mn and Co, respectively; in the other site, the corresponding hyperfine fields are negative, with the values −6.0 T and −6.9 T. The dynamic hyperfine interaction of Mn in ZrZn₂ has also been studied using the thermal cyclic method with a weak thermal link, and was analyzed for the two relaxation times corresponding to the different lattice sites.     

Endoscopic microsuture repair of vocal fold defects

The presence of a nonvibratory segment of vocal folds after microlaryngeal surgery is often a cause of poor voice result. The etiology of a nonvibratory segment is due to full thickness epithelial defect followed by secondary wound closure and scar contracture. To reduce scar contracture and nonvibratory segment of the vocal folds, primary repair with a 6-0 chromic endo-knot suture technique was used to close defects and approximate microflaps of the vocal folds. This was done in 18 patients with epithelial defects after resection of benign vocal fold lesions. The pathologic findings included severe polypoid degeneration (n = 7), fusiform laryngeal polyps (n = 5), sulcus vocalis (n = 2), cyst (n = 2), and keratosis (n = 2). Voice was improved in all patients after surgery. Comparison of vocal fold vibration before and after surgery showed improvements in configuration, amplitude, and mucosal wave. Vocal folds that were sutured all had good vibratory characteristics; none had a nonvibrating segment at the site of suture placement. Voice and healing after microsuture technique were near normal by Day 10 and return of mucosal wave was often complete by Day 14. Endoscopic microsuture closure of microflaps of the vocal folds edge is safe and affords the surgeon an opportunity for primary repair with improved functional result.     

Precision nuclear orientation measurements for determining mixed magnetic dipole/electric quadrupole hyperfine interactions

We report the temperature dependence of the gamma-ray anisotropies from oriented¹⁶⁰Tb nuclei produced by neutron activation of the central portion of a high-purity single crystal Tb slab. The magnetically saturated sample was studied over a wide temperature range from 18 mK to 150 mK. The temperatures were determined using precision resistance thermometry within situ calibration by a magnetically shielded six-element superconducting fixed point device. Temperature stability during data acquisition was better than 0.1%, and least-squares fitting of the resulting temperature dependences of 0° and 90° anisotropies allowed both the magnetic dipole and the electric quadrupole hyperfine interaction frequencies to be determined with good accuracy. The weighted averages for 18 gamma rays arev _M=1393.8 (8.1) MHz andv _P=178.0 (2.1) MHz, in excellent agreement with NMR results on ion-implanted samples.