Asymmetric Total Syntheses,Stereostructures, and Cytotoxicities of Marine Bromotriterpenoids Aplysiol B (Laurenmariannol) and Saiyacenol A

There are marine cytotoxic bromotriterpenoids, named the thyrsiferol family that are structurally characterized by some tetrahydropyran (THP) and tetrahydrofuran (THF) rings. The thyrsiferol family belongs to natural products that are often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic tetrasubstituted carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, to elucidate ambiguous stereostructures and unassigned absolute configurations of aplysiol B, laurenmariannol, and saiyacenol A, members of the thyrsiferol family, we carried out their asymmetric chemical syntheses featuring 6-exo and 5-exo oxacyclizations of epoxy alcohol precursors and 6-endo bromoetherification of a bishomoallylic alcohol. In this paper, we report total assignments of their stereostructures through their asymmetric chemical syntheses and also their preliminary cytotoxic activities against some tumor cells. These results could not have been achieved without depending on asymmetric total synthesis.     

Gelation of fluorinated liquids by non-fluorinated low-molecular-mass molecules

A family of tetrahydroxy diesters has been synthesised and observed to gel a range of fluorinated solvents and their mixtures; the phase behaviour and gel microstructure are reported for a homologous family of these diesters in blends of 1H,1H-heptafluorobutanol (HFB) and 2H,3H-perfluoropentane (HPFP).     

CMMSE2017: On two classes of fourth- and seventh-order vectorial methods with stable behavior

A family of fourth-order iterative methods without memory, for solving nonlinear systems, and its seventh-order extension, are analyzed. By using complex dynamics tools, their stability and reliability are studied by means of the properties of the rational function obtained when they are applied on quadratic polynomials. The stability of their fixed points, in terms of the value of the parameter, its critical points and their associated parameter planes, etc. give us important information about which members of the family have good properties of stability and whether in any of them appear chaos in the iterative process. The conclusions obtained in this dynamical analysis are used in the numerical section, where an academical problem and also the chemical problem of predicting the diffusion and reaction in a porous catalyst pellet are solved.     

Bignoniaceae metabolites as semiochemicals

Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds). The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.     

Terpenoid alkaloids of the Buxaceae family with potential biological importance

The plants of the family Buxaceae are widely used in traditional medicine and constitute rich sources of terpenoidal alkaloids. Compounds of this family have been the subject of numerous chemical and pharmacological studies over past decades because of their interesting biological activities such as cholinesterase inhibition, as well as antibacterial and antileishmanial activities. The chemical and biological properties of these alkaloids, including data relevant to straightforward structure determination and information on biosynthesis, are highlighted in this review, with 144 references being cited.     

Caspases: key mediators of apoptosis

Recent studies have established that members of the caspase protease family are essential components of a conserved cell death program. Insights into their biological roles, structure and mechanism are enabling investigators to begin to explore the therapeutic potential of caspase inhibition.     

Etude Des Spectres de Masse Des Constituants Amers Des Simarubacées

The bitter compounds isolated from the species Simaroubaceae represent a new family of degraded triterpenoids. Ailanthone, glaucarubolone and chaparrinone having a C₂₀ skeleton belong to this family and their structures were previously determined. Mass spectra of these compounds and some of their derivatives have now been studied in detail and the results obtained are discussed in this communication. The observed fragmentation pattern is characteristic of the structural features of this group of compounds.     

NMR solution structure of a photoswitchable apoptosis activating Bak peptide bound to Bcl-xL

The Bcl-2 family of proteins includes the major regulators and effectors of the intrinsic apoptosis pathway. Cancers are frequently formed when activation of the apoptosis mechanism is compromised either by misregulated expression of prosurvival family members or, more frequently, by damage to the regulatory pathways that trigger intrinsic apoptosis. Short peptides derived from the pro-apoptotic members of the Bcl-2 family can activate mechanisms that ultimately lead to cell death. The recent development of photocontrolled peptides that are able to change their conformation and activity upon irradiation with an external light source has provided new tools to target cells for apoptosis induction with temporal and spatial control. Here, we report the first NMR solution structure of a photoswitchable peptide derived from the proapoptotic protein Bak in complex with the antiapoptotic protein Bcl-x(L). This structure provides insight into the molecular mechanism, by which the increased affinity of such photopeptides compared to their native forms is achieved, and offers a rationale for the large differences in the binding affinities between the helical and nonhelical states.     

Principles of RNA base pairing: structures and energies of the trans Watson-Crick/sugar edge base pairs

Due to the presence of the 2'-OH hydroxyl group of ribose, RNA molecules utilize an astonishing variability of base pairing patterns to build up their structures and perform the biological functions. Many of the key RNA base pairing families have no counterparts in DNA. In this study, the trans Watson-Crick/sugar edge (trans WC/SE) RNA base pair family has been characterized using quantum chemical and molecular mechanics calculations. Gas-phase optimized geometries from density functional theory (DFT) calculations and RIMP2 interaction energies are reported for the 10 crystallographically identified trans WC/SE base pairing patterns. Further, stable structures are predicted for all of the remaining six possible members of this family not seen in RNAs so far. Among these novel six base pairs, the computations substantially refine two structures suggested earlier based on simple isosteric considerations. For two additional trans WC/SE base pairs predicted in this study, no arrangement was suggested before. Thus, our study brings a complete set of trans WC/SE base pairing patterns. The present results are also contrasted with calculations reported recently for the cis WC/SE base pair family. The computed base pair sizes are in sound correlation with the X-ray data for all WC/SE pairing patterns including both their cis and trans isomers. This confirms that the isostericity of RNA base pairs, which is one of the key factors determining the RNA sequence conservation patterns, originates in the properties of the isolated base pairs. In contrast to the cis structures, however, the isosteric subgroups of the trans WC/SE family differ not only in their H-bonding patterns and steric dimensions but also in the intrinsic strength of the intermolecular interactions. The distribution of the total interaction energy over the sugar-base and base-base contributions is controlled by the cis-trans isomerism.     

Synthesis and reactivity of an unprecedented osmium(VIII) alkylidene

The synthesis of a family of Os(VIII) alkylidene complexes, the highest oxidation state alkylidenes known to date, and their reactivity toward small organic molecules are reported.     

Performance of the M06 family of exchange-correlation functionals for predicting magnetic coupling in organic and inorganic molecules

The performance of the M06 family of exchange-correlation potentials for describing the electronic structure and the Heisenberg magnetic coupling constant (J) is investigated using a set of representative open-shell systems involving two unpaired electrons. The set of molecular systems studied has well defined structures, and their magnetic coupling values are known experimentally. As a general trend, the M06 functional is about equally as accurate as B3LYP or PBE0. The performance of local functionals is important because of their economy and convenience for large-scale calculations; we find that M06-L local functional of the M06 family largely improves over the local spin density approximation and the generalized gradient approximation.     

Capillary electrophoresis of glucosinolates and their degradation products

Glucosinolates are important natural products occurring mainly in plants of the Cruciferae family. This review article is aimed at describing the recent progress made in capillary electrophoresis of glucosinolates and their degradation products. It describes the various electrophoretic systems and detection schemes introduced to date for the capillary electrophoresis (CE) of glucosinolates and their degradation products. Also included in this review are the applications of CE to the qualitative and quantitative determination of glucosinolates and their degradation products in plant extracts.     

Discovery, structure and biological activities of the cyclotides

The cyclotides are a family of small disulfide rich proteins that have a cyclic peptide backbone and a cystine knot formed by three conserved disulfide bonds. The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling. They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity. There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years. Ultimately the family may comprise thousands of members. This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries. Their unique topological features make them interesting from a protein folding perspective. Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection.     

Locating the cyclopentano cousins of the cucurbit[n]uril family

The synthesis of the first family of fully substituted cucurbit[n]uril is discussed, and the structural features of precursor glycolurils are highlighted in their importance to achieving higher homologues. The members of the family, where n = 5-7, have been fully characterized, and increased binding affinities have been identified for dioxane in CyP(6)Q[6] and adamantyl NH(3)(+) in CyP(7)Q[7]. A higher homologue is indicated but not conclusively identified.     

Synthesis of 5-alkylidene-1,3-dioxane-4,6-diones, an easily accessible family of axially chiral alkenes: preparation in non-racemic form and platinum binding studies

A general synthetic route to 5-alkylidene-1,3-dioxane-4,6-diones, which are a family of axially chiral alkenes, is described. Conformational issues are explored and the platinum-binding properties of these species are discussed. That these alkenes exist as stable enantiomers is established by their partial kinetic resolution upon reaction with cysteine.     

The design, synthesis, and characterization of the first cavitand-based de novo hetero-template-assembled synthetic proteins (Hetero-TASPs)

The design, synthesis, and characterization of novel cavitand-based hetero-TASPs, TASPs having different peptide sequences within one bundle, are described. Three families of hetero-TASPs were designed: the LG3/LG2 family (different linker lengths), LG3/AG3 family (altering helix hydrophobicity), and the LG3/LG2C family (anti-parallel caviteins). These first generation hetero-TASPs were found to be alpha-helical, stable towards guanidine hydrochloride, and monomeric in solution. The LG3/LG2 caviteins exhibited primarily native-like properties. The remaining hetero-TASP families were found to exhibit less dispersion and broader signals in the amide regions of their (1)H NMR spectra than their respective reference caviteins. The success in the design of the LG3/LG2 hetero-TASPs suggests that subsequent hetero-TASPs may have potential to manifest superior native-like structure compared with homo-TASPs, and refinement of the linker and peptide sequences may accomplish this goal.     

The Dutch Resolution variant of the classical resolution of racemates by formation of diastereomeric salts: family behaviour in nucleation inhibition

The resolution of racemates through their diastereomeric salts can be positively affected by the addition of small amounts of suitable nucleation inhibitors. This discovery is a logical extension of "Dutch Resolution", in which equimolar amounts of resolving agents that are members of the same family (i.e., structurally related) are used. We conducted a systematic search for nucleation inhibitors of the resolving agent 1-phenylethylamine. A wide range of amines that bear possible family resemblances to 1-phenylethylamine was investigated. It was found that (R)-1-phenylbutylamine is a good inhibitor of (R)-1-phenylethylamine. Results of turbidity measurements showed that, for the model case of mandelic acid resolution, the chief effect of this inhibitor was to widen the metastable zone for the more soluble diastereomer. This observation is in accordance with previous experience. Further scouting for possible family members revealed a wide variation in the effectiveness of inhibitors, dependent on their structure. By far the most effective inhibitors are bifunctional 1-phenylethylamine and/or 1-phenylbutylamine analogues. The effect of racemic inhibitors was found to approach that of enantiomerically pure inhibitors of the same absolute configuration of the 1-phenylethylamine used for resolution. The most effective inhibitors were tested for the resolution of a structural variety of racemates, and were shown to be broadly applicable.     

基于四氢喹啉酸骈环戊烯骨架的蛋白酪氨酸磷酸酶1B抑制剂的设计、合成及构效关系

基于肿瘤、糖尿病等重大疾病的有限目标,选择蛋白酪氨酸磷酸酶(PTPs)家族这一生物体系中有代表性的PTP家族成员PTP1B,SHP-1,SHP-2,LAR,CDC25B及PRL-3进行研究.通过综合高通量筛选获得的"苗头"化合物结构信息,分析得到四氢喹啉骈环戊烯骨架.初步的构效关系研究表明,四氢喹啉酸骈环戊烯母核结构可...     

Peptoids as source of compounds eliciting antibacterial activity

N-Alkylglycine oligomers (peptoids) constitute a family of non-natural peptidomimetics attractive for the early drug discovery process because of their physicochemical features, easy of adaptation to combinatorial chemistry approaches and their proteolytic stability. Consequently, peptoid libraries have found application for discovering hits against a wide diversity of pharmaceutical targets, among which different examples of antibacterials are found. In the present work, research efforts addressed towards the identification of peptoids as antibacterial agents are discussed.