Synthesis of a muscarinic receptor antagonist via a diastereoselective Michael reaction, selective deoxyfluorination and aromatic metal-halogen exchange reaction

An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.     

Laser-induced plasma by two-color excitation

With a superposition of a nanosecond infrared-laser pulse and its second harmonic, the threshold of plasma formation in gasses as well as the energy transfer efficiency from the laser field to the plasma can be significantly improved in comparison to purely monochromatic radiation. We present experimental results in air at pressures between 0.4 and 3 bar; in this pressure range, the threshold energy for the superposition is reduced by ≈30% as compared to that of pure infrared radiation, while the energy transfer slope efficiency is equal to the IR efficiency at high pressures and somewhat less at lower pressures. Possible mechanisms responsible for this effect are discussed.     

雾化角对液体火箭发动机燃烧室压力振荡的影响

针对液氧/煤油火箭发动机模型燃烧室实现了三维非稳态两相燃烧过程的数值模拟,得到的燃烧室截面平均压力和平均速度与实验吻合。在初边值条件不施加任何扰动的情况下,得到了燃烧室压力自激振荡过程,并研究了液氧和煤油喷嘴雾化角对燃烧室压力振荡的影响。计算结果表明:当雾化角为40°或120°时,由于燃料与氧化剂喷雾锥重叠区域较小或较大,导致了推进剂混合很差或很好,不易在燃烧室头部出现局部爆炸性的可燃混气团,致使燃烧室压力振荡强度较弱;而当雾化角为中间值65°时,易于出现爆炸性的可燃气团并导致剧烈的压力振荡,使燃烧室中出现燃烧不稳定性。因此,雾化角的合理设计是抑制燃烧不稳定性的一种途径。     

内蒙古地区沙生植物--沙枣中维生素C含量的测定

在 pH 6.0的 HAc-NaAc缓冲溶液中,用活性炭吸附沙枣中的色素,Cu(Ⅱ)催化氧化维生素C,在λmax=268 nm处可直接测定沙枣中维生素C含量.与传统碘量法相比,测定结果基本一致.为内蒙古地区沙枣天然植物资源的药用开发、食品加工等提供了参考数据.     

Laser Diode-Pumped Nd：LuVO4 Acousto-Optic Q-Switched Laser at 916 nm

A compact laser diode-pumped solid-state Nd：LuVO4 acousto-optic Q-switched laser is demonstrated at 916 nm of a quasi-three level for the first time. A pulse width of 130ns is observed when the pulse-repetition frequency is 10 kHz. The laser experiment shows that the Nd：Lu VO4 crystal can be used for efficient diode-pumped Q-switched lasers.     

Coherence artifacts in second harmonic microscopy

We present an analysis of these effects and demonstrate a simple, yet powerful technique to eliminate these coherence artifacts. The technique relies on a superposition of the signal field with a coherent auxiliary SH-field of controllable phase and amplitude and allows a direct observation of the true χ⁽²⁾-morphology of the interface. Recieved: 20 September 1998     

A highly enantioselective catalyst for asymmetric hydroformylation of [2.2.1]-bicyclic olefins

Rh(CO)₂(acac)/TangPhos was found to be a highly enantioselective catalyst for asymmetric hydroformylation of norbornylene under mild conditions. Application of the protocol to the desymmetrization of other [2.2.1]-bicyclic olefins gave moderate to excellent enantioselectivity (55-92% ee).     

Intraventricular thrombus formation in the LVAD-assisted heart studied in a mock circulatory loop

Left ventricular assist devices (LVADs) are mechanical pumps that are surgically attached to the left ventricle and aorta. Clinical studies show that LVADs improve patient health and quality of life, and dramatically reduce the mortality of cardiac failure. During periods of high LVAD support, blood flow occurs entirely through the LVAD, the aortic valve is continuously closed, and the heart operates in series with the pump. Thus the normal fluid dynamics of intraventricular flow are altered and linked to the development of thrombus in both the native heart and LVAD. Our goal in this study was to simulate a patient with a recurring thrombus and quantify the variations in the flow field in the LV as the thrombus developed. Particle image velocimetry measurements of transparent silicone models were performed for a range of LVAD support conditions. Results show that the presence of a small thrombus in the LVOT creates a favorable condition for further growth, especially in the presence of high LVAD support. As the thrombus enlarges, it begins to affect the normal vortex-flow pattern, further reducing flow rate and pulsatility in the LVOT. Evaluation of vortex dynamics and stasis regions in both patients and experimental models of LVAD support yield quantitative metrics that can be used to assess the risk of thrombus and the development of strategies to reduce this risk in LVAD patients.     

Solvent-dependent dynamic kinetic asymmetric transformation/kinetic resolution in molybdenum-catalyzed asymmetric allylic alkylations

Catalytic asymmetric alkylation reactions of branched racemic carbonates 1a and 1b with sodium dimethyl malonate, promoted by molybdenum and ligand 5, proceed by a kinetic resolution in toluene, THF, tetrahydropyran, i-PrOAc, 1,2-dichloroethane, and MeCN with k(rel) of 7-16. In THF, MeCN, tetrahydropyran, and i-PrOAc using the (S,S)-5 ligand, the fast reacting (S)-carbonate enantiomer provides the branched product with high ee (97-99.5%) and branched/linear selectivity, but the ee erodes as the reaction of the slow-reacting (R)-enantiomer takes place. This implies that the rate of equilibration of the oxidative addition complexes in these solvents is competitive with the subsequent malonate displacement step. In toluene and dichloroethane, the ee and branched/linear ratios diminish during the reaction of the slow-reacting (R)-isomer, but not nearly as much as in the other solvents. This is most likely due to either an increase in the rate of equilibration of the oxidative addition complexes relative to the malonate displacement step, or vice versa. Because of the minimal stereochemical memory effect in toluene and 1,2-dichloroethane, the reactions in these solvents can be carried to completion (dynamic kinetic asymmetric transformation) and still provide product with excellent ee (>95%). The anion of dimethyl methylmalonate also reacts via a kinetic resolution, although the ee's, rates, and k(rel) values differ from those of the reactions with dimethyl malonate.