硫手性有机小分子催化剂的设计、合成及其在不对称亚胺氢转移还原中的应用

过去十多年，世界手性药物市场需求迅速增长，手性制药工业的发展壮大，已经引起了各国政府、学术界，特别是企业界的高度重视。手性药物中含有大量的手性胺单元，因此研究高效构建手性胺结构单元的方法具有重要的意义和实用价值，而亚胺的不对称还原是合成手性胺最便捷的方法。 手性有机小分子路易斯碱催化三氯氢硅不对称还原亚胺是最近几年才发展起来的一类新的亚胺不对称还原方法。尽管在对映选择性和底物适用范围等方面已经获得了突破性的进展，但是，高性能的路易斯碱催化剂仅局限于N-甲酰氨基酸酰胺一种类型，而且其底物适用范围和催化活性仍不够理想。因此，发展新型催化剂很有必要。 手性硫氧化物作为手性诱导剂的应用已经有数十年的时间，广泛应用在不对称合成及天然产物的全合成中。理论上，硫氧结构单元也可以作为路易斯碱，对硅烷类试剂进行活化，而且硫氧键还有碳氧键难以比拟的先天优势，硫原子自带手性特征，在反应过程中，手性中心离反应位点更近，因此，从手性硫氧化合物出发，极有可能开发出新的高效手性路易斯碱催化剂。最近，Kobayashi和Khiar在亚胺的不对称烯丙基化反应中用手性亚砜活化烯丙基三氯硅烷，获得了较好的ee值，但反应中手性亚砜的用量都需要化学计量以上，因此还不能算做真正意义上的催化剂，进一步的文献调研也未见真正意义上的硫手性有机小分子催化剂。 本文首次成功将硫手性亚磺酰胺衍生物应用于催化三氯氢硅对亚胺的不对称还原，在经过对亚磺酰胺衍生物的多次结构优化，开发出了合成容易，催化活性和立体选择性都很优良，并且有着前所未有的底物普适性的新型手性路易斯碱催化剂。 我们首先尝试将商品化的20mol%叔丁基亚磺酰胺和对甲基亚磺酰胺直接用作催化剂催化三氯氢硅对亚胺的不对称还原，尽管仅获得中等的收率和很低的对映选择性，但证明我们的设计思路是可行的。在此基础上，我们以叔丁基亚磺酰胺为原料和基本骨架，设计合成了一系列的亚磺酰胺类催化剂，通过对催化剂的结构改造，发现当催化剂中存在较强酸性的酚羟基时，催化效果得到大幅提高。随着对催化剂的进一步结构优化，我们找到了一个结构简单，催化效果还不错的催化剂，经过反应条件优化以后，催化反应的收率最高能达到98%，对映选择性最高达93%，并且这个催化剂的底物适应范围比之前报道的催化剂都要广泛。针对酚羟基在催化剂中的重要作用，我们进行了仔细的机理研究后发现，在催化反应中，催化剂极有可能是通过双分子机理去活化三氯氢硅从而实现不对称催化的，而酚羟基的作用就是通过分子间氢键促进双分子催化剂与三氯氢硅的络合。受此启发，我们设计了一系列具有双齿结构的催化剂，通过对双齿催化剂的结构优化，最终筛选出了一个结构更加简单，但催化效果更好的双齿催化剂。10mol%该催化剂催化亚胺还原最高获得95%的收率和96%的ee值。这一结果也进一步验证了我们先前对催化剂机理的推测。 随后，我们还尝试将这些催化剂用于二级胺和芳香酮的直接还原胺化反应中，虽然能获得不错的收率，但对映选择性却很差，我们对反应条件进行了仔细的摸索，仍然没有获得突破。但这些实验为进一步研究二级胺和酮的不对称直接还原胺化反应奠定了良好的基础。 In the past decade, the rapid growth of the global chiral drug market and the significant development of the chiral pharmaceutical industry have attracted a great deal of attention from government, academia and enterprises. Chiral amine is an important structural motif of chiral drugs. Therefore, development of methods for the construction of this motif is of great importance. Catalytic enantioselective reduction of imines represents one of the most straightforward and efficient methods for the preparation of chiral amines. The chiral Lewis base organocatalysts promoted asymmetric reduction of imines by HSiCl3 has recently achieved significant advancements. Although big breakthroughs have been made in terms of substrate generality and enantioselectivity, the highly effective catalysts are limited to N-formyl amino acid amides, of which the efficiency and substrate scope remain unsatisfactory. Therefore, development of novel organocatalysts for this transformation is in great demand. Chiral sulfoxides have been well established as efficient and versatile stereocontrollers and have been extensively used in asymmetric synthesis and total synthesis of natural products. The S=O structural motif of sulfoxide could also behave as Lewis base activator for cholorsilane reagents, which, moreover, could be even better than caboxamide considering that the sulfur atom is chiral and thus the chirality center is closer to the reaction center. There exist great potentials that highly effective novel Lewis base organocatalysts could be developed starting from S-chiral sulfoxides. Recently, several S-chiral sulfoxides were reported by Kobayashi and Khiar to be used as Lewis base catalyst to activate allyltrichlorosilanes in asymmetric allylations and good enantioselectivities were obtained. However, these S-chiral sulfoxides were all used at a more than stoichiometric amount and were thus not authentically catalytic. A careful literature survey further revealed that there has been so far no S-chiral organocatalyst available. In this study, we, for the first time, successfully used S-chiral sulfinamides as Lewis base organocatalysts for the asymmetric reduction of ketimines by HSiCl3. After several rounds of structural optimization, we developed the first example of highly effective S-chiral organocatalysts, which promoted the asymmetric reduction of ketimines with trichlorosilane in high yield and excellent enantioselectivity with unprecedented substrate spectrum. In our initial practice, we examined 20mol% of the commercially available (R)-tert-butanesulfinamide and (S)-toluenesulfinamide as the catalyst in the hydrosilylation of ketimine. Although the product was only furnished in moderate yield and low ee, these results demonstrated that our strategy of catalyst design is on the right way. Next, starting from chiral tert-butanesulfinamide, we prepared a series of tert-butanesulfinamide derivatives via simple reductive amination and examined their catalytic efficiencies in the reduction of ketimine. We found that the catalyst bearing a phenolic hydroxyl group exhibited good reactivity and enantioselectivity. On the basis of which, we obtained a structurally simple and highly effective novel organocatalyst, affording the product in 98% yield and 93% ee under optimal reaction conditions. After careful exploration on the role of phenolic hydroxyl group in the catalyst, we speculated that two molecules of the catalyst be involved in the course of reaction, of which the assembly around the silicon center is facilitated by the intermolecular hydrogen bonding through the phenolic hydroxyl groups. Thus, we incorporated two units of sulfonamide into one molecular and prepared a new type of bissulfinamides organocatalysts and examined their catalytic efficiencies in the reduction of ketimine. After optimizing the structure of these catalysts, we finally obtained a novel organocatalyst which has even simpler molecular structure but showed better efficacies, 10mol% of which afforded up to 97% yield and 96% ee under optimal reaction conditions. These results further proved our speculation about the catalytic mechanism. We also examined the newly developed S-chiral organocatalysts in direct asymmetric reductive amination of secondary amines with aromatic ketone. The product was furnished in good yield but in low ee. No better results could be obtained despite our intense opimization efforts. Nevertheless, these experiments laid excellent foundations for eventual success.

Optoelectronic quotient-selected modified signed-digit division

A novel optoelectronic quotient-selected modified signed-digit division technique is proposed. This division method generates one quotient digit per iteration involving only one shift operation, one quotient selection operation and one addition/subtraction operation. The quotient digit can be selected by observing three most significant digits of the partial remainder independent of the divisor. Two algorithms based on truth-table look-up and binary logic operations are derived. For optoelectronic implementation, an efficient shared content-addressable memory based architecture as well as compact logic array processor based architecture with an electron-trapping device is proposed. Performance evaluation of the proposed optoelectronic quotient-selected division shows that it is faster than the previously reported convergence division approach. Finally, proof-of-principle experimental results are presented to verify the effectiveness of the proposed technique. (C) 2001 Society of Photo-Optical Instrumentation Engineers.

LBO晶体上1064，532nm倍频增透膜的镀制及性能分析

用电子束蒸发沉积方法在X切LBO（X-LBO）晶体上镀制了两种不同膜系结构的1064和532nm倍频增透膜，其中一种膜系结构为基底／ZrO2／Y2O3／A12O3／SiO2／空气，另一种为基底／0．5Al2O3／ZrO2／Y2O3／A12O3／SiO2／空气，两种膜系结构的主要差别在于有无氧化铝过渡层。测量了薄膜的反射率光谱曲线，发现两种增透膜在1064和532nm处的反射率均小于0．5％，实际镀制结果与理论设计曲线的差异主要是由材料折射率的变化引起的。且对样品在空气环境中进行了温度为473K的退火处理，

Rate-equation-based circuit model of high-speed semiconductor lasers

Based oil rare equations of semiconductor laser, a symbolically-defined model for optical transmission system performance evaluation and network characterization in both time- and frequency domains is presented. The steady-state and small-signal characteristics, such as current-photon density curve, current-voltage curve, and input impedance, call be predicted from this model. Two important dynamic characteristics, second-order harmonic distortion and two-tone third-order intermodulation products, are evaluated under different driving conditions. Experiments show that the simulated results agree well with the published data. (c) 2007 Wiley Periodicals, Inc.

曙光5000A天体大规模数值模拟软件性能测试

在国产百万亿次超级计算机曙光5000A上进行了天体大规模数值模拟软件的性能和可扩展测试实验,详细介绍了软件中的测试程序以及测试环境和过程,并对测试结果进行了分析.对于80×80×50的网格规模,采用每节点4进程测试了16～128个处理器核,每节点8进程、16进程分别测试了16～512个处理器核,相对加速比最终分别达到5.33、10.48和12.57,并行效率分别达到66.66%、32.58%和32.29%.对于160×160×100的网格规模,测试了每节点16进程的64～8192个核的性能,最大相对加速比为12.46,并行效率为9.73%.测试结果表明,曙光5000A具有良好的性能,测试结果对软件下一步的优化研究具有重要的指导意义.

集群网络评测模型的新探索

传统集群网络(cluster area network,简称cLAN)的评测模型主要考虑了延迟、带宽、路由、拥塞、网络拓扑结构等因素.但这些因素是否足以描述实际应用程序在集群上的通信行为,或者对其在集群系统上的性能给出一个很好的预测呢?当对NAS Parallel Benchmark(2.4版本)在集群系统深腾1800(DeepComp 1800)上进行大量测试时发现,集群网络的通信性能可以被一种特殊的通信模式(LU模式)所严重影响.更深入的研究表明,这个影响LU模式的因素是独立于前面所述的如延迟、带宽、路由、拥塞、网络拓扑结构等因素的.因此有必要对集群网络的评测模型重新进行审视,并增加一个新的性能评测因子以反映这个新发现的现象.从研究结果来看,这个重新审视也将对集群系统上的并行算法设计以及实际大规模科学计算的应用程序性能的优化提供一些新的思路.

国产万亿次机群系统NPB性能测试分析

对3个国产万亿次机群系统进行了NPB性能测试分析,重点研究大规模并行处理时(处理器数目达到上千个)的性能特点和趋势.分析了不同的处理器、互连网络等系统配置对NPB性能的影响,发现NPB的8个程序在3个万亿次机器上的性能特点和表现并不一致,表明国产高性能机群在设计上正在逐渐走出同质化的趋势,向多样化发展.进一步分析表明,目前NPB程序的可扩展性可以达到几百个处理器,但尚不能达到上千个处理器,NPB程序能发挥出的系统峰值的百分比仍然徘徊在10%左右,机群系统的并行可扩展性和应用程序对机器运算潜能的利用还需要进一步提高.对于处理器数目达到上千个的万亿次机群系统来说,对集合通信和细粒度通信能力的支持亟需提高.

两种线程池的实现和性能评价

线程池被广泛地应用在中间件如Web应用服务器、事务监控器等的实现中。实现线程池的方法主要有半同步/半异步(Half-Sync/Half-Asyn)模式和领导者/跟随者(Leader/Follower)模式。实现了这两种线程池,从理论上分析了它们的性能,并进行了性能实验。实验数据表明Leader/Follower模式具有较高的性能优势。

VCSTalk:基于DEA的开源软件开发人员效率评价工具

介绍了VCSTalk的具体设计和实现架构,并展示了它用于评价若干开源软件项目中的开发人员效率的一个具体实例.

Approximate analytical optical transfer function for a wavefront-coded imaging system with two-dimensional rectangularly separable phase masks

Wavefront coding can be used to extend the depth of field of incoherent imaging systems and is a powerful system-level technique. In order to assess the performance of a wavefront-coded imaging system, defocused optical transfer function (OTF) is the metric frequently used. Unfortunately, to the best of our knowledge, among all types of phase masks, it is usually difficult to obtain the analytical OTF except the cubic one. Although numerical computation seems good enough for performance evaluation, the approximate analytical OTF is still indispensable because it can reflect the relationship between mask parameters and system frequency response in a clearer way. Thus, a method is proposed to derive the approximate analytical OTF for two-dimensional rectangularly separable phase masks. The analytical results are well consistent with the direct numerical computations, but the proposed method can be accepted only from engineering point of view and needs rigorous proof in future. (c) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3485759]