Total Synthesis of Crocagin A

Crocagin A ( 1 ) combines an attractive molecular structure with an unusual biosynthesis and bioactivity. An efficient synthesis of crocagin A is presented that hinges on an early formation of the heterotricyclic core, an electrophilic amination, and the stereoselective hydrogenation of a tetrasubstituted double bond. This synthesis confirms the absolute configuration of crocagin A and provides access to the natural product and derivatives thereof for further biological testing.     

Preliminary communication Lyotropic mesomorphism of AB block copolymers in a nematic solvent

A lyotropic hexagonal mesophase is identified in a mixture of a low molecular mass nematic solvent and an AB block copolymer with a liquid crystalline block A and an isotropic block B by polarizing microscopy. A highly ordered striated texture evolves spontaneously that exhibits an additional striated fine structure within the stripe domains.     

纳米粒子/共聚物混合体系结构的Monte Carlo模拟

基于简立方格点模型,对纳米粒子/共聚物混合体系进行了动力学Monte Carlo模拟研究. 每一共聚物链均由一个A珠子和三个B珠子组成,表示为A1B3. A1B3链的两亲性体现为B-B之间的相互吸引作用,同时憎水性的纳米粒子之间也存在相互吸引. 通过适当选取纳米粒子与B珠子之间的吸引作用势,观察到两种结构:纳米粒子/A1B3链的核-壳结构和纳米粒子分散在憎水壳层中的A1B3囊泡结构. 还研究了这两种结构的动力学演化过程,模拟结果表明在纳米粒子分散于囊泡壳层的过程中A1B3囊泡起模板作用.     

Phase behaviors of nematic liquid crystal/linear polymer systems: Effect of specific interactions

A new model has been proposed that takes into account the specific interaction between nematic liquid crystal and polymer. A generalized lattice fluid model was employed to describe the specific interaction between liquid crystal and polymer. The proposed model postulates that a specific interaction between dissimilar components in a mixture has both an energetic and an entropic component. A degeneracy parameter and an interaction parameter are also discussed, followed by a comparison of the experimental data to the model. The results show that that a specific interaction plays an important role in the phase behaviors of the given systems. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4128–4136, 2000     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.     

A walk around the A3-coupling

In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A(3)-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A(3)-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A(3)-coupling as well as different tandem reactions involving A(3)-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A(3)-couplings and related transformations.     

Synthesis and biological activities of 4-phenyl-5-pyridyl-1,3-thiazole derivatives as selective adenosine A3 antagonists

To investigate the potency of an adenosine A3 receptor (A3AR) antagonist as an anti-asthmatic drug, a novel series of 4-phenyl-5-pyridyl-1,3-thiazole derivatives was synthesized and evaluated in human adenosine A1, A2A and A3 receptor and rat adenosine A3 receptor binding assays. From investigation of the SAR study, compound 7af was identified as a highly potent human and rat A3AR antagonist. This compound inhibited IB-MECA-induced plasma protein extravasation in the skin of rats and showed good oral absorption. Also, compound 7af significantly inhibited antigen-induced hyper-responsiveness to acetylcholine in actively sensitized Brown Norway rats. These results show that 4-phenyl-5-pyridyl-1,3-thiazole derivatives are potential candidates to enable the evaluation of A3AR antagonists. Further evaluation of this class of compounds may afford a novel anti-inflammatory agent such as an anti-asthmatic drug.     

Synthesis of A-B-C-ring Tricyclic Core of iso-Merrilactone A

A desymmetrization approach for the synthesis of the A-B-C tricycle intermediate of iso-merrilactone A was described. The key steps of this synthesis to efficiently access the tetracyclic Illicium sesquiterpenes core included an intramolecular aldol cyclization and an oxidative lactonization reaction. A novel Au catalyzed hydrolytic cyclorearrangement cascade reaction was explored in the initial stage.     

Recent research and development of DYRK1A inhibitors

Dual specificity tyrosine phosphorylation regulated kinase 1 A(DYRK1 A) is an evolutionarily conserved protein kinase belonging to the CMGC kinase family, which is closely related to Down syndrome(DS)and Alzheimer’s disease(AD). In recent years, not only the treatment of diabetes, but also the treatment of cancer gradually focuses on targeting DYRK1 A. Therefore, a series of DYRK1 A inhibitors have been developed to treat relevant diseases and clarify their treatment mechanism furtherly. DYRK1 A...     

RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits translation initiation

Eukaryotic initiation factor 4A (eIF4A) is a member of the DEAD-box family of putative RNA helicases whose members are involved in many aspects of RNA metabolism. eIF4A is thought to facilitate binding of 43S preinitiation complexes to mRNAs by unwinding secondary structures present in the 5' untranslated region. Pateamine A, a small-molecule inhibitor of translation initiation, acts in an unusual manner by stimulating eIF4A activity. Herein, we report the elucidation of pateamine's mode of action. We demonstrate that Pateamine A is a chemical inducer of dimerization that forces an engagement between eIF4A and RNA and prevents eIF4A from participating in the ribosome-recruitment step of translation initiation.     

Efficient excitation energy transfer in long meso-meso linked Zn(II) porphyrin arrays bearing a 5,15-bisphenylethynylated Zn(II) porphyrin acceptor

Electronically coupled porphyrin arrays are suitable for artificial light harvesting antenna in light of a large absorption cross-section and fast excitation energy transfer (EET). Along this line, an artificial energy transfer model system has been synthesized, comprising of an energy donating meso-meso linked Zn(II) porphyrin array and an energy accepting 5,15-bisphenylethynylated Zn(II) porphyrin linked via a 1,4-phenylene spacer. This includes an increasing number of porphyrins in the meso-meso linked Zn(II) porphyrin array, 1, 2, 3, 6, 12, and 24 (Z1A, Z2A, Z3A, Z6A, Z12A, and Z24A). The intramolecular singlet-singlet EET processes have been examined by means of the steady-state and time-resolved spectroscopic techniques. The steady-state fluorescence comes only from the acceptor moiety in Z1A-Z12A, indicating nearly the quantitative EET. In Z24A that has a molecular length of ca. 217 A, the fluorescence comes largely from the acceptor moiety but partly from the long donor array, indicating that the intramolecular EET is not quantitative. The transient absorption spectroscopy has provided the EET rates in real time scale: (2.5 ps)(-1) for Z1A, (3.3 ps)(-1) for Z2A, (5.5 ps)(-1) for Z3A, (21 ps)(-1) for Z6A, (63 ps)(-1) for Z12A, and (108 ps)(-1) for Z24A. These results have been well explained by a revised F?rster equation (Sumi formula), which takes into account an exciton extending coherently over several porphyrin pigments in the donor array, whose length is not much shorter than the average donor-acceptor distance. Advantages of such strongly coupled porphyrin arrays in light harvesting and transmission are emphasized in terms of fast EET and a large absorption cross-section for incident light.     

Dual Crosslinking Photo-Switches for Orthogonal Photo-Control of Hybridization Between Serinol Nucleic Acid and RNA

Wavelength-selective photo-regulation by multiple chromophores responding to different wavelengths can expand the variation of photo-manipulating systems. Herein, we report the orthogonal photo-regulation of duplex formation between serinol nucleic acid (SNA) and RNA using light-induced crosslinking reactions mediated by a new photo-reactive nucleobase 8-naphthylvinyladenine (^NVA) and previously described 8-pyrenylvinyladenine (^PVA). An intrastrand crosslink was induced in an SNA strand containing two adjacent ^NVA residues by irradiation with 340–405 nm light; the crosslink was reversed by irradiation with ≤300 nm light. In an SNA strand with adjacent ^NVA and ^PVA residues, an intrastrand crosslink resulted from irradiation with 405–465 nm light that was reversed by irradiation with ≤340 nm light. Intrastrand photo-crosslinking caused severe destabilization of an SNA/RNA duplex, resulting in dissociation to single strands. Cycloreversion resulted in duplex formation. With these ^NVA/^NVA and ^NVA/^PVA photo-switches, four hybridization states of two SNA/RNA duplexes could be orthogonally photo-controlled by irradiation with a suitable wavelength of light.     

Hopeahainol A: an acetylcholinesterase inhibitor from Hopea hainanensis

A phytochemical study of Hopea hainanensis has led to the isolation of three new polyphenols and one known compound. The most important of these compounds are hopeahainols A (2) and B (3), which contain an unprecedented carbon skeleton. The structures were elucidated by analysis of the spectroscopic data including single-crystal X-ray spectroscopy and computational methods. Hopeahainol A was an acetylcholinesterase inhibitor with an IC50 value of 4.33 microM, which is comparable to that of huperzine A, a presently prescribed drug for the treatment of Alzheimer, while other similar structures were inactive. This observation was complemented by a 3D interaction model of the inhibitor with active sites.     

Isolation and Asymmetric Total Synthesis of Perforanoid A

A novel limonoid, perforanoid A, was isolated, and an asymmetric total synthesis was achieved in 10 steps. The key steps are chiral tertiary aminonaphthol mediated enantioselective alkenylation of an aldehyde to an allylic alcohol, Pd‐catalyzed coupling of the allylic alcohol with vinyl ether to form the γ‐lactone ring, and cyclopentenone ring formation through a Rh‐catalyzed Pauson–Khand reaction. Preliminary studies show that perforanoid A is cytotoxic towards HEL, K562, and CB3 tumor cell lines.     

Molecularly asymmetric triblock copolymers as a single-molecule route to ordered bidisperse polymer brushes

The conditions signaling the formation of bidisperse brushes in ordered block copolymers are investigated as an A(2) block is progressively grown onto an A(1)B diblock copolymer to form a series of molecularly asymmetric, isomorphic A(1)BA(2) triblock copolymers. Small-angle scattering and self-consistent field theory confirm that the microphase-ordered period decreases when the A(2) block is short relative to the A(1) block, but then increases as A(1)+A(2) bidisperse brushes develop. The mechanical properties systematically follow the spatial distribution of the A(2) block.     

Total Synthesis of (−)‐Nakadomarin A

A highly efficient 12‐step synthesis of the marine alkaloid (?)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (?)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.     

Absolute characterization of laser-induced breakdown spectroscopy detection systems

A quantitative comparison of the performance of four different laser-induced breakdown spectroscopy detection systems is presented. The systems studied are an intensified photodiode array coupled with a Czerny–Turner spectrometer, an intensified CCD coupled with a Czerny–Turner spectrometer, an intensified CCD coupled to an Echelle spectrometer, and a prototype multichannel compact CCD spectrometer system. A simple theory of LIBS detection systems is introduced, and used to define noise-equivalent spectral radiance and noise-equivalent integrated spectral radiance for spectral detectors. A detailed characterization of cathode noise sources in the intensified systems is presented.     

Chemical synthesis and immunological evaluation of entirely carbohydrate conjugate Globo H-PS A1

An anticancer, entirely carbohydrate conjugate, Globo H-polysaccharide A1 (Globo H-PS A1), was chemically prepared and immunologically evaluated in C57BL/6 mice. Tumor associated carbohydrate antigen Globo H hexasaccharide was synthesized in an overall 7.8% yield employing a convergent [3 + 3] strategy that revealed an anomeric aminooxy group used for conjugation to oxidized PS A1 via an oxime linkage. Globo H-PS A1, formulated with adjuvants monophosphoryl lipid A and TiterMax® Gold. After immunization an antigen specific immune response was observed in ELISA with anti-Globo H IgG/IgM antibodies. Specificity of the corresponding antibodies was determined by FACS showing cell surface binding to Globo H-positive cancer cell lines MCF-7 and OVCAR-5. The anti-Globo H antibodies also exhibited complement-dependent cellular cytotoxicity against MCF-7 and OVCAR-5 cells.

An anticancer, entirely carbohydrate conjugate, Globo H-polysaccharide A1 (Globo H-PS A1), was chemically prepared and immunologically evaluated in C57BL/6 mice.     

Ring closing and opening reactions leading to aza-polycyclic aromatic compounds

A series of functionalized aza-polycyclic aromatic compounds were prepared by a superacid-promoted ring closing and opening reaction cascade. A reaction mechanism is proposed, which involves reactive dicationic intermediates. A key step in the conversions involves ipso protonation of an aryl group and elimination of an alkyl phenyl group.     

Synthesis of pyrazine alcaloids from Botryllus leachi. Diazines 43

[reaction: see text] Regioselective metalation of pyrazines and cross-coupling reactions provides an easy access to botryllazines A and B and to an isomer of botryllazine A with good yields from chloropyrazine.