Synthesis of the EF-ring of ciguatoxin 3C based on the [2,3]-Wittig rearrangement and ring-closing olefin metathesis

The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27 bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing olefin metathesis for the F-ring formation.     

Novel branched ether formation via conjugate reduction of an unsaturated cyanohydrin derivative and its synthetic application to the EF-ring segment of ciguatoxin

A synthetic method for a branched ether system was developed. The method was based on Lewis-acid-promoted γ-position selective reduction of a γ-alkoxy β,γ-unsaturated α-silyloxy nitrile, prepared through a process including intermolecular hetero-Michael reaction of a 2-butynoate ester derivative with an alcohol. The method was efficiently applied to the synthesis of fused medium-ring ethers involving the EF-ring segment (2) of ciguatoxin (1).     

Synthesis of the EF-ring segment of ciguatoxin CTX1B based on novel regioselective reduction of unsaturated cyanohydrins and ring-closing olefin metathesis

Aiming at a convergent total synthesis of ciguatoxin CTX1B, its EF-ring segment has been synthesized. During the synthesis, a novel method for the construction of branched ethers, based on regioselective reduction of γ-alkoxy β,γ-unsaturated α-silyloxy nitriles with borontrifluoride etherate and trialkyl silane or tributyltin hydride, has been developed. Combination use of the method and ring-closing olefin metathesis successfully provided medium-sized cyclic ethers. Efficient site-selective reduction of vinyl epoxides into homoallyl alcohols has also been developed.     

An Ireland–Claisen rearrangement/RCM based approach for the construction of the EF-ring of ciguatoxin 3C

The EF-ring of ciguatoxin 3C, a marine toxin from the dinoflagellate Gambierdiscus toxicus, was stereoselectively synthesized by iterative use of a cyclic ether formation process based on chirality-transferring Ireland-Claisen rearrangement and ring-closing olefin metathesis.     

Biomimetic synthetic studies on lactonamycin: an expedient synthesis of dihydroxy-isoindolinone-carboxylates

The synthesis of dihydroxy-isoindolinone-carboxylates from a dioxinone keto-ester and N-protected sarcosine without the use of phenolic protection is described. Base-induced aromatization of the dioxinone diketo-ester followed by lactamization furnished the desired dihydroxy-isoindolinone moiety, which could be used as an EF-ring precursor toward the synthesis of lactonamycin.     

一种蓝色荧光材料的合成

本文设计和合成了一种带有吡唑啉侧链基因的低聚酰胺,可用作蓝色荧光材料。分子中特殊的氢键序列(AADADD)及芳酰胺链可与制着器件所用的高分子基材分子之间的形成较强的作用力,从而将发光基团“铆定”在功能膜中。     

An improved synthesis of the C42–C52 segment of ciguatoxin 3C

In our previously reported method for the construction of the IJKLM-ring of ciguatoxin 3C (CTX3C), the lengthy synthetic process for the intermediate C42–C52 (L-ring) segment was problematic. Therefore, a new and improved procedure for the C42–C52 segment, having modified protecting groups, was developed. The new route includes a chirality transferring Ireland-Claisen rearrangement for the construction of the vicinal dimethyl branching at C47–48, a one-pot cyclization process for the establishment of the stereocenters at C45 and C46 as well as the γ-hydroxy δ-lactone framework corresponding to the L-ring, and Brown’s asymmetric crotylboration for the installation of the stereocenters at C43 and C44. The new C42–C52 segment was successfully coupled with the previously reported C32–C41 (I-ring) segment to produce the IJKLM-ring.     

残基突变对P53-DNA结合域肽段构象影响的分子动力学模拟

基于分子动力学模拟方法研究了R249S、R248W 和G245S 突变对P53-DNA 结合域肽段(残基230-258)结构的影响. 采用GROMACS 软件包和GROMOS 43A1分子力场, 分别对野生型wtP53肽段、单点突变型P53-R249S肽段、两点突变型P53-R249S/R248W肽段和三点突变型P53-R249S/R248W/G245S肽段进行了4组独立的分子动力学模拟, 每组体系模拟时间为500 ns. 研究结果表明: R249S单残基突变影响肽段残基形成二级结构的情况, 但不改变肽段三维结构的模式, 同时使该肽段结构相对稳定; R249S和R248W两残基同时突变会加剧R249S突变对肽段的影响, 同时导致三维结构发生较大变化, 构象弯曲呈现双turn 结构, 肽段稳定性进一步增大; G245S突变对肽段的影响与R249S和R248W同时突变对其结构的影响相反, 在两残基突变的基础上, G245S突变会使原突变引起的变化减弱甚至消失, 同时使得该肽段结构稳定性减小. 该研究对认识肿瘤致病分子机制和设计新药物有重要意义.     

Synthesis of new side‐group liquid crystalline block copolymers by living anionic polymerization

A new series of AB liquid crystalline (lc) block copolymers was synthesized via living anionic copolymerization of styrene as segment A and 6‐[4‐(4‐cyanophenylazo)phenoxy]hexyl methacrylate ( 1 ) as segment B. The copolymers were successfully prepared in quantitative yields and with narrow molar mass distributions. The number‐average molar mass of the segments was varied well‐defined. The polystyrene block ranged from 3 500 to 7 400 g/mol. The content of the B segment ranged from 1 to 54 wt.‐%. Thermotropic phases were detected by differential scanning calorimetry (DSC) for block copolymers with an lc segment of more than 30 wt.‐%.     

CAMDA扩链聚氨酯脲的硬段对形态与性能的影响

由红外光谱、核磁共振及质谱分析证实了所合成的3-氯-3’-甲氧基-4,4’-二氨基二苯基甲烷(CAMDA)具有预期的化学结构.用RIM方法制成的CAMDA基聚氨酯脲(PUU)性能接近于DETDA扩链的PUU.用快速手工浇注法制备了一系列由CAMDA扩链的不同硬段含量的PUU样品.采用DSC、SEM观察了硬段含量由10％增加到45％PUU形态的变化,并测量了力学性能.实验结果表明:随着硬段含量增加,PUU的形态由平行间隔的软、硬链段富集区经相互穿叉的软、硬段富集区,进一步聚集成硬链段富集球状超级结构,强度亦相应提高.     

共轭/非共轭嵌段聚苯撑乙烯(PPV)类共聚物的合成与性能

用活性中间体直接引发共轭/非共轭单体聚合的新方法合成了3种PPV嵌段共聚物;用核磁共振谱和FTIR光谱确定了共聚物的结构.引入非共轭片段PS缩短了PPV共轭链的长度,改善了聚合物的溶解性和可加工性.荧光光谱结果表明,嵌段聚合物可使发射峰蓝移,发光的量子效率明显提高,进而调节了发光颜色.     

A segment contribution method for the vapor pressure of tall-oil chemicals

A segment-contribution method for the estimation of vapor pressure of large, oligomeric molecules encountered in oleochemical industry is described. The method makes use of segment composition, number of segments, and four parameters per segment to estimate vapor pressure as a function of temperature. For major components that occur in crude tall-oil (CTO) distillation, the optimum parameters are reported and the method is shown to be accurate. The open architecture of this segment contribution approach permits the use of new segments, or the treatment of whole molecules as segments if necessary.     

Influence of the structure on thermoset cure kinetics

The influence of molecular structure on cure kinetics was studied using a new approach for characterizing the cure kinetics of thermosets in the glass transition region. Reactions in or near the glassy state are controlled by chain mobility, where the whole structural unit undergoes small-angle oscillation motions around the network link. All structural features affecting the mobility such as stiffness, bulky structures, substitution, symmetry effects, and functionality lead to high segment activation energies and slow final curing. The influence of the segment activation energy on the kinetic curves is also discussed. © 1993 John Wiley & Sons, Inc.     

Theoretical modeling of the relationship between Young's modulus and formulation variables for segmented polyurethanes

We describe a new modeling approach to prediction of Young's modulus of segmented polyurethanes. This approach combines micromechanical models with thermodynamic considerations based on the theory of block copolymers. The resulting model predicts both the equilibrium morphology and the “ideal” Young's modulus of a segmented polyurethane polymer as a function of its formulation (hard segment chemical structure, hard segment weight fraction, soft segment equivalent weight) and temperature. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2123–2135, 2007     

Computer Simulations for the Growth Process of Peanut-Type Hematite Particles

The growth process of a monodispersed peanut-type hematite particle consisting of much smaller elongated subcrystals has been reproduced by computer simulation. On the basis of the microscopic internal structure, the simulation was performed by replacing the sequential events of surface nucleation and the subsequent growth of each subcrystal in the actual process with an arranged deposition of rectangular segments of fixed dimensions under different conditions in their site-dependent deposition rate and in the flexibility of their tilt angles. The most successful simulation model was obtained on the assumptions of a relatively fast deposition of the segments on the outermost side-surface of the ellipsoidal particle and the flexible tilt angle of each segment depending on the position of a neighboring new segment placed afterward. The result of the simulation strongly supported the previous elucidation of the growth mechanism in terms of the outward bending of adjoining subcrystals by nucleation and growth of a new subcrystal in each space between them. Enhancement of the outward bending of subcrystals by a large amount of sulfate ions adsorbed to the growing subcrystals was also suggested. Copyright 1999 Academic Press.     

Synthesis of amphiphilic block copolymer using trimethylene carbonate bearing oligo(ethylene glycol) and investigation of thin film including cilostazol

To prepare a thin film, the block copolymer poly(TMCM-MOE3OM)-b-PTMC was prepared with different segment ratios of hydrophilic moiety. The glass transition temperature of poly(TMCM-MOE3OM)-b-PTMC decreased as the content of TMCM-MOE3OM increased as expected, and it was confirmed that the graft oligo(ethylene glycol) (OEG) affected intermolecular interaction. The polymers grafted with OEG showed a thermoresponsive property, which can be expected to be applied to materials triggered by temperature. A thin film was prepared by mixing block copolymer and cilostazol as a drug, and the distribution of cilostazol was observed. It was confirmed that cilostazol was uniformly distributed on the thin film and that local sustained release could be avoided at the time of elution. The eluting behavior of the thin film from the substrate was apparently affected on the segment ratio of the block copolymer. When the thin film was immersed in PBS, the eluting rate increased as the segment ratio of TMCM-MOE3OM in the block copolymer increased. As a result, it is possible to control the eluting rate by changing the ratio of the hydrophilicity and the hydrophobicity of the block copolymer, contributing to the creation of a new coating material containing cilostazol.     

Microstructure and properties of polyurethanes derived from castor oil

The goal of this work was the synthesis of novel segmented polyurethanes with a high percentage of components derived from renewable sources. The soft segment was a polyol derived from castor oil and the hard segment structure was varied by means of different chain extenders, petrochemical-based 1,4-butanediol (BD) and corn sugar-based 1,3-propanediol (PD). The synthesis was carried out in bulk and without catalyst via a two-step polymerization varying hard segment ratio. Physico-chemical, mechanical and morphological characterization was performed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), atomic force microscopy (AFM), mechanical testing and termogravimetric analysis (TGA). Properties have been discussed from the viewpoint of hard/soft microdomain phase separation and also the hard segment nature and formed structure. An increase in hard segment content was accompanied by an increase in hard domain order, crystallinity, and stiffness. The hard segment structures, in addition to the elastic nature of soft segment, provide enough physical crosslink sites to impart properties ranging from elastomeric to rigid behaviour with the increase of hard segment content. Polyurethanes synthesized from bio-based chain extender showed a slightly lower crystallinity in the hard segment structure than that synthesized from BD as the chain extender. This lower crystallinity avoids strength concentrations at the soft/crystalline hard segment interface, thus improving the mechanical properties at high hard segment content. The slightly higher thermal stability observed for BD based polyurethanes is related with their more packed structures and crystallinity observed in the hard segment structure.     

Synthesis and characterization of hydrolysable poly(ether-urethane-urea)s derived from l-leucine anhydride cyclopeptide; a green synthetic method for monomer

l-leucine anhydride cyclodipeptide (LAC) was prepared through a green method under microwave irradiation with good yield. Then a new class of hydrolysable poly(ether-urethane-urea)s (PEUUs) was synthesized via two-step polymerization method. In the first step, 4,4′-methylene-bis-(4-phenylisocyanate) (MDI) was reacted with LAC to produce isocyanate-terminated poly(imide-urea) oligomers (hard segment). Reaction of the resulting pre-polymer with different molecular weights (MW) of polyethyleneglycols (PEG)s such as PEG-400, PEG-600, PEG-1000 and PEG-2000 was the second step to furnish a series of new PEUUs. The resulting multiblock copolymers have inherent viscosities in the range of 0.4-1.8 dL/g. These multiblock copolymers are hydrolysable, thermally stable and soluble in amide-type solvents. Polymers containing different molecular weights of PEGs soft segments show different thermal stability, phase separation, hard segment cohesiveness and hydrolysis rate. Some structural characterization and physical properties of these PEUUs are reported.     

Design of Oligourea-Based Foldamers with Antibacterial and Antifungal Activities

There is an urgent need to develop new therapeutic strategies to fight the emergence of multidrug resistant bacteria. Many antimicrobial peptides (AMPs) have been identified and characterized, but clinical translation has been limited partly due to their structural instability and degradability in physiological environments. The use of unnatural backbones leading to foldamers can generate peptidomimetics with improved properties and conformational stability. We recently reported the successful design of urea-based eukaryotic cell-penetrating foldamers (CPFs). Since cell-penetrating peptides and AMPs generally share many common features, we prepared new sequences derived from CPFs by varying the distribution of histidine- and arginine-type residues at the surface of the oligourea helix, and evaluated their activity on both Gram-positive and Gram-negative bacteria as well as on fungi. In addition, we prepared and tested new amphiphilic block cofoldamers consisting of an oligourea and a peptide segment whereby polar and charged residues are located in the peptide segment and more hydrophobic residues in the oligourea segment. Several foldamer sequences were found to display potent antibacterial activities even in the presence of 50% serum. Importantly, we show that these urea-based foldamers also possess promising antifungal properties.     

Synthesis and characterization of novel environmentally friendly shape memory polyurethanes based on poly(epsilon-caprolactone) diol/castor oil mixtures

A new category of polyurethane plastics (PUs) was obtained from poly (ε-caprolactone) diol/castor oil mixture as a dual-component of their soft segment and hexamethylene diisocyanate (HDI) as the hard segment. The main aim of this study was to explore the effect of castor oil on content chemical structure, dynamic and mechanical properties and low temperature heat induced shape memory of the obtained polyurethane system. The chemical structure of samples was confirmed by Fourier transforms infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Differential scanning calorimetry (DSC) was carried out to study thermal transitions of synthesized polyurethanes. At 50 mol % of oil, the polyurethane showed the highest enhancement in tensile strength (54%) and Young’s modulus (23%) compared to PU-0. The PU containing 50 mol % of oil was nearly recovered by 99%.