吲哚生物碱Desbromoarborescidine A 的全合成及烯胺C-亚磺酰化反应研究

从新几内亚核桃木的树皮中分离得到的吲哚类喹诺里西定生物碱10-Desbromoarborescidine A，因发现其具有阻滞钙离子通道的活性而倍受关注。10-Desbromoarborescidine A由A、B、C、D四个环组成，只有一个手性中心，是吲哚生物碱中结构较简单的一种，常作为此类生物碱全合成方法的模型化合物。但迄今为止，能高效而简便的实现手性10-Desbromoarborescidine A不对称全合成方法线路不多，大多数以不对称诱导的方式建立其手性中心，手性催化的方式仅有一例金属催化。从逆合成分析可知，Desbromoarborescidine A的全合成可以通过亚胺不对称催化还原进行关键的手性中心构建，而本课题组在之前的研究中通过手性有机小分子催化剂的发展，已将三氯硅烷氢转移还原亚胺发展成了一类简便实用、高效、高对映选择性并具有优良底物适应范围的不对称催化反应，我们希望以这一反应作为关键手段，发展一条Desbromoarborescidine A及其类似物不对称合成新路线。 根据我们设计的新路线，首先成功合成了其关键中间体，然后我们进行了关键的不对称催化尝试。用本实验室已有的高性能有机小分子催化剂虽得到了较好的对应选择性，但是产率很低。同时，为了验证整条线路的可行性，我们也用消旋的中间体进行拉通线路的尝试。但不幸的是，在脱除保护基时遇到了很大困难。尝试换不同的保护基，或改变脱保护基的顺序，都未能成功合成目标产物。究其原因可能是由于吲哚的特殊性造成的，吲哚类亚胺与常规的芳香亚胺有较大的差异，其NH基团无论保护还是不保护，对与其2位相联接的C=N双键均有很大的影响，导致其不对称催化还原难以进行。另外，由于所设计的还原产物含有处在吲哚苄位的胺基，稳定性较差，造成保护基脱除困难。 烯胺C-亚磺酰化反应是本课题组最近发现的一个新反应，之前未见文献报道。本研究对该反应进行了反应条件优化和底物扩展，发现带Cbz，Ac，COt-Bu，CO2Et，Bz等保护基的一系列环状和非环状烯胺在亚磺酸钠、DMAc和MeSiCl3的共同作用下能高效高产率生成β-胺基烯基亚砜类新化合物，为合成多官能团化的烯基亚砜新化合物提供了一条简便实用的途径。 The main constituent of Dracontomelum mangiferum B1, indoloquinolizidine alkaloid 10-Desbromoarborescidine A, has drawn great attention due to its calcium channel blocking activity. Its molecular structure is relatively simple compared with the other alkaloids of the same type, which has only one chiral center, albeit with four cycles A, B, C, and D. This compound is often used as a model target for exploring different strategies for the total synthesis of indole alkaloids. Nevertheless, so far there still lack practical and highly efficient methods for the asymmetric total synthesis of 10-Desbromoarborescidine A. Most of the current available methods rely on stoichiometric asymmetric synthesis for the construction of the chiral center. There is only one example reporting utilization of asymmetric catalysis, but with transition metal complex as the catalyst. Our retrosynthetic analysis shows that catalytic asymmetric reduction of imine could be used as the key step for the construction of the chiral center of Desbromoarborescidine A. Since in the previous studies our group has developed the asymmetric reduction of imines by trichlorosilane into a practical and highly efficient and enantioselective method using newly designed chiral organocatalysts, we hope to apply this method to develop a novel synthetic route for the total synthesis of Desbromoarborescidine A and its analogues in this study. According to the newly designed synthetic route, we first accomplished the synthesis of the key intermediates which was then examined for the critical asymmetric catalysis. The asymmetric reduction using the highly efficient organocatalysts, developed in our lab afforded high ee but poor yield. We tried different reaction conditions to improve the yield, but failed to get any good results. Simultaneously, to vertify the feasibility of the synthetic route we designed, we also tired to go through the route toward the racemic synthesis of Desbromoarborescidine A. But unfortunately, protection and deprotection proved to be big hurdles. All the different protection groups and different sequences of protection and deprotection we tried failed to get us through the designed synthetic sequence and furnish the final product. Most likely, the indole part is the culprit behind the failures.The NH group of the indole, no matter protected or not, may impact the catalytic asymmetric reduction of C-N double bond connected with 2-C. Additionally, the reduction product we designed contains an amino group in the β-position of the indole, which may cause problems due to its instability. C-sulfenylation of enamines is a novel reaction discovered recently by our group, which has not been seen before in the literature. In this study, optimization of the reaction conditions and exploration of the substrate scope were further undertaken for this reaction, which reveal that a series of enamines with N-Cbz, Ac, COt-Bu, CO2Et protection groups could all undergo smooth C-sulfinylations with the comined use of sodium benzene sulphinate, DAMc and MeSiCl3, efficiently furnishing the β-amino vinylsulfoxide products in high yield, affording a practical and highly efficient methods for synthesis of functional vinylsulfoxides.

Entrance-channel dependence of isospin effects on double n/p ratio in HIC

Within the hadronic transport model IBUU04, we investigate the effect of density-dependent symmetry energy on double neutron/proton (n/p) ratio of free nucleons in heavy ion collisions by taking four isotopic Sn+Sn reaction systems. Especially the entrance-channel asymmetry and impact-parameter dependence of the effect of symmetry energy are discussed. It is found that in both central and semi-central collisions the sensitivity of the double n/p ratio to the density-dependent symmetry energy is more pronounced in neutron-richer systems. Our results also indicate clearly that the effect of symmetry energy is stronger in central collisions than that in semi-central collisions.

Effect of entrance-channel asymmetry on the isospin dependence of nucleon emission in heavy ion collisions

Using the isospin- and momentum-dependent hadronic transport model 1BUU04, we have investigated the influence of the entrance-channel isospin asymmetry on the sensitivity of the pre-equilibrium neutron/proton ratio to symmetry energy in central heavy-ion collisions induced by high-energy radioactive beams. Our analysis and discussion are based on the dynamical simulations of the three isotopic reaction Systems Sn-132+Sn-124, Sn-124+Sn-112 and Sn-112+(112)Su which are of the same total proton number but, different isospin asymmetry. We find that, the kinetic-energy distributions of the pre-equilibrium neutron/proton ratio are quite sensitive to the density-dependence of symmetry energy at incident beam energy E/A = 400 MeV, and the sensitivity increases as the isospin asymmetry of the reaction system increases.

Entrance channel dependence of the correlation function of IMFs in Ar-36+Sn-112,Sn-124 at 35MeV/u

The reduced velocity correlation functions of the Intermediate Mass Fragments (IMFs) were measured in the reactions of Ar-36+ Sn-112,Sn-124 at 35MeV/u. The anti-correlation at small reduced velocities is more pronounced in Ar-36+ Sn-124 system than that in Ar-36+ Sn-112 system. The difference of the correlation functions between the two reactions is mainly contributed by the particle pairs with high momenta. A three-body Coulomb repulsive trajectory code (MENEKA) is employed to calculate the emission time scale of IMFs for-the both systems. The time scale is 150fm/c in the Ar-36+ Sn-112 system and 120fm/c in the Ar-36+ Sn-124 system, respectively. A calculation based on an Isospin dependence Quantum Molecular Dynamics code (IQMD) reveals that the emission time spectrum of IMFs is shifted slightly leftwards in Ar-36+ Sn-124 compared with that in the Ar-16+ Sn-112 system, indicating a shorter emission time scale. Correspondingly, the central density of the hot nuclei decreases faster in Ar-36+ Sn-124 than in Ar-36+ Sn-112

Entrance channel effects on the role of isospin-dependent momentum interaction in isospin fractionation in heavy ion collisions

An isospin degree of freedom is inserted into the momentum dependent interaction in the quantum molecular dynamics model to obtain an isospin dependent momentum interaction given in a form practically usable in isospin dependent quantum molecular dynamics model. We investigate the entrance channel effects for the role of isospin momentum dependent interaction on the isospin fractionation ratio and its dynamical mechanism in the intermediate energy heavy ion collisions. It is found that the isospin dependent momentum interaction induces a significant reduction of isospin fractionation ratio under all entrance channel conditions. However the strong dependence of isospin fractionation ratio on the symmetry potential is preserved after considering the isospin degree of freedom in the momentum dependent interaction.

新型多道高精度的时间-电压转换电路系统的设计；A Design of New Multi-channel High Precision Time-to-amplitude Convert (TAC) Circuit

在发展髙性能多路小型化前端电路方面,阐述了一种用于测试时间的系统电路的设计与实现。其突出特点是转换速度快,电路结构简单,输入信号范围大、精度高、功耗低,电路采用改进的TAC方法,用于处理快速的时间信号,利用高速DMOS开关,并优化控制逻辑时序,极大提高了测试精度。

Development of multi-channel gated integrator and PXI-DAQ system for nuclear detector arrays

A multi-channel gated integrator and PXI based data acquisition system have been developed for nuclear detector arrays with hundreds of detector units. The multi-channel gated integrator can be controlled by a programmable Cl controller. The PXI-DAQ system consists of NI PXI-1033 chassis with several PXI-DAQ cards. The system software has a user-friendly GUI which is written in C language using LabWindows/CVI under Windows XP operating system. The performance of the PXI-DAQ system is very reliable and capable of handling event rate up to 40 kHz. (C) 2010 Elsevier B.V. All rights reserved.

64通道一维位置灵敏电流分布探测器及其数据获取系统；A 64-Channel Position Sensitive Current Distribution Detector with Data Acquisition System

针对高流强粒子束与绝缘毛细管相互作用的特点,设计制作了一套64通道一维位置灵敏电流分布探测器及其配套的数据获取系统,该探测器可分辨最小直径为1mm的束斑,通过数据获取系统可实现可视化自动数据采集。用2nA和200—2000eV电子对探测器进行了定标,并用10μA和2000eV的电子束穿越锥形毛细管后的出射电子,对探测器及数据获取系统进行测试,获得了出射粒子的位置分布谱及能量信息。

PIC mode simulation of solenoid collimation channel

A new SSC (Separated Sector Cyclotron)-Linac is being designed to serve as an injector for the SSC at the HIRFL (Heavy Ion Research Facility Lanzhou). The beam intensity at the LEBT (Low Energy Beam Transport) for the heavy ions after the selection is typically low and the space charge effects are inconspicuous. The space charge effects become obvious when the beam current increases to a few hundred microamperes. The emittance growth deriving from the space charge effects may be particularly troublesome for the following linac and cyclotron. An optical system containing three solenoids has been designed for the LEBT to limit the beam emittance and to avoid the unnecessary beam loss in the cyclotron, as well as for the purpose of immunizing the LEBT emittance growth due to the space charge effects. The results of the PIG (Particle-In-Cell) mode simulation illustrate that this channel could limit the beam emittance growth and increase the beam brightness.