Cu(I)-catalyzed tandem benzyldiazoester coupling with terminal alkyne-allene formation-Michael reaction: application to the syntheses of oxa and azacycles

A simple and practical procedure for the synthesis of aza- and oxacycles, which possess an array of stereogenic functionalities, is described. This protocol relies on tandem Cu-catalyzed coupling of suitably functionalized terminal alkyne with diazoester followed by isomerization and subsequent aza or oxa-Michael reaction, thus generating the required scaffold with high diastereoselectivity.     

Nonlinear Resonances Leading to Strong Pulse Attenuation in Granular Dimer Chains

We study nonlinear resonances in granular periodic one-dimensional chains. Specifically, we consider a diatomic (“dimer”) chain composed of alternating “heavy” and “light” spherical beads with no precompression. In a previous work (Jayaprakash et al. in Phys. Rev. E 83(3):036606, 2011) we discussed the existence of families of solitary waves in these systems that propagate without distortion of their waveforms. We attributed this dynamical feature to “antiresonance” in the dimer that led to the complete elimination of radiating waves in the trail of the propagating solitary wave. Antiresonances were associated with certain symmetries of the velocity waveforms of the dimer beads. In this work we report on the opposite phenomenon: the break of waveform symmetries, leading to drastic attenuation of traveling pulses due to radiation of traveling waves to the far field. We use the connotation of “resonance” to describe this dynamical phenomenon resulting in maximum amplification of the amplitudes of radiated waves that emanate from the propagating pulse. Each antiresonance can be related to a corresponding resonance in the appropriate parameter plane. We study the nonlinear resonance mechanism numerically and analytically and show that it can lead to drastic attenuation of pulses propagating in the dimer. Furthermore, we estimate the discrete values of the normalized mass ratio between the light and heavy beads of the dimer for which resonances are realized. Finally, we show that by adding precompression the resonance mechanism gradually degrades, as does the capacity of the dimer to passively attenuate propagating pulses.     

Three-dimensional energy channeling in the unit-cell model coupled to a spherical rotator II: unidirectional energy channeling

In order to realize the dynamic response analysis and the chaos identification of flexible spatial parallel mechanism, the nonlinear elastic dynamics model of 4-UPS-UPU flexible parallel mechanism is established under the ideal situation, and the dynamic response, phase diagrams, Poincare map and largest Lyapunov exponent of the spatial parallel mechanism are investigated. Based on the finite element method, the driving limbs of spatial parallel mechanism are divided into elements. The kinetic energy equation and potential energy equation of units are built. Then the nonlinear elastic dynamics model of 4-UPS-UPU parallel mechanism is acquired by Lagrange equation. The dynamic response of kinematic error for 4-UPS-UPU flexible parallel mechanism is analyzed. In addition, the chaos phenomenon contained in the mechanism is identified by phase diagrams, Poincare map and largest Lyapunov exponent, respectively. Subsequently, the relationship between the basic parameters of parallel mechanism and largest Lyapunov exponent is discussed. The results indicate that there exists chaotic phenomena in the 4-UPS-UPU flexible parallel mechanism, and the basic parameters, including the material of driving limbs, diameter of driving limbs, mass of moving platform and the distribution radius of hinges of moving platform all have great effect on chaotic motion of 4-UPS-UPU flexible parallel mechanism. The researches can provide important theoretical for the further nonlinear dynamics behaviors research and optimal design of 4-UPS-UPU flexible spatial parallel mechanism.     

Singular Lyapunov spectra and conservation laws

We give analytic arguments and numerical evidence to show that the presence of conservation laws can produce a singularity in the spectrum of Lyapunov exponents for extended dynamical systems of low spatial dimensionality. This phenomenon can be used, e.g., for finding hidden conservation laws. (c) 1995 American Institute of Physics.     

Sequence‐Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications

The functionality of natural biopolymers has inspired significant effort to develop sequence‐defined synthetic polymers for applications including molecular recognition, self‐assembly, and catalysis. Conjugation of synthetic materials to biomacromolecules has played an increasingly important role in drug delivery and biomaterials. We developed a controlled synthesis of novel oligomers from hydroxyproline‐based building blocks and conjugated these materials to siRNA. Hydroxyproline‐based monomers enable the incorporation of broad structural diversity into defined polymer chains. Using a perfluorocarbon purification handle, we were able to purify diverse oligomers through a single solid‐phase extraction method. The efficiency of synthesis was demonstrated by building 14 unique trimers and 4 hexamers from 6 diverse building blocks. We then adapted this method to the parallel synthesis of hundreds of materials in 96‐well plates. This strategy provides a platform for the screening of libraries of modified biomolecules.     

Cell-permeable esters of diazeniumdiolate-based nitric oxide prodrugs

Although O(2)-(2,4-dinitrophenyl) derivatives of diazeniumdiolate-based nitric oxide (NO) prodrugs bearing a free carboxylic acid group were activated by glutathione to release NO, these compounds were poor sources of intracellular NO and showed diminished antiproliferative activity against human leukemia HL-60 cells. The carboxylic acid esters of these prodrugs, however, were found to be superior sources of intracellular NO and potent inhibitors of HL-60 cell proliferation.     

Efficient chemical synthesis of a dodecasaccharidyl lipomannan component of mycobacterial lipoarabinomannan

Lipomannan (LM) is one of the domains of lipoarabinomannan (LAM) glycolipids, the latter being one of several cell surface organic molecules that fortify mycobacterial species against external attack. Some members of mycobacterial families are pathogenic, most notably Mycobacterium tuberculosis and Mycobacterium leprae, while others are nonpathogenic, and used in the clinic, such as Mycobacterium smegmatis. Additional biological significance arises from the fact that LM has been implicated in several health disorders outside of those associated with mycobacterial pathogens, notably for treatment of bladder cancer. LM is comprised of a heavily lipidated phosphoinositide dimannoside headgroup, from which a mannan array, of varied complexity, extends. The latter consists of a 1,6-alpha-linked backbone flanked at position O2, not necessarily regularly, with alpha-linked mannosides. This paper gives an example of lipomannan synthesis in which all of the sugar components, whether functioning as donors or acceptors, are obtained from n-pentenyl orthoesters, themselves in turn prepared in three easy steps from D-mannose. Assembly of the mannan array is facilitated by the exquisite regioselectivity occasioned by the use of ytterbium triflate/N-iodosuccinimide as the trigger for reaction of n-pentenyl orthoesters.     

Stereoselective total synthesis of paecilomycin E and F and its two congeners Cochliomycin C and 6-epi-Cochliomycin C

An efficient and concise approach to the total synthesis of Paecilomycins E (1) and F (2), Cochliomycin C (4) and 6-epi-Cochliomycin C (3) is described. The synthesis involves novel route to the synthesis of Paecilomycin E and F and further conversion to Cochliomycin C and 6-epi-Cochliomycin C. Olefin metathesis and base promoted macro lactonization being the key reactions followed by chlorination to achieve target Cochliomycin C and 6-epi-Cochliomycin C.