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At least 847 records · Page 47Linked to original sources
PubMed2003

Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus.

BACKGROUND: Convergence extension movements are conserved tissue rearrangements implicated in multiple morphogenetic events. While many of the cell behaviors involved in convergent extension are known, the molecular interactions required for this process remain elusive. However, past evidence suggests that regulation of cell adhesion molecule function is a key step in the progression of these behaviors. RESULTS: Antibody blocking of fibronectin (FN) adhesion or dominant-negative inhibition of integrin beta 1 function alters cadherin-mediated cell adhesion, promotes cell-sorting behaviors in reaggregation assays, and inhibits medial-lateral cell intercalation and axial extension in gastrulating embryos and explants. Embryo explants were used to demonstrate that normal integrin signaling is required for morphogenetic movements within defined regions but not for cell fate specification. The binding of soluble RGD-containing fragments of fibronectin to integrins promotes the reintegration of dissociated single cells into intact tissues. The changes in adhesion observed are independent of cadherin or integrin expression levels. CONCLUSIONS: We conclude that integrin modulation of cadherin adhesion influences cell intercalation behaviors within boundaries defined by extracellular matrix. We propose that this represents a fundamental mechanism promoting localized cell rearrangements throughout development.

Animals↗
PubMed2003

Convergent evolution of cucurbitacin feeding in spatially isolated rootworm taxa (Coleoptera: Chrysomelidae; Galerucinae, Luperini).

Historically, chemical ecologists assumed that cucurbitacin feeding and sequestration in rootworm leaf beetles is a remnant of an ancient association between the Luperini (Coleoptera: Chrysomelidae; Galerucinae) and Cucurbitaceae (ancestral host hypothesis). Under this premise, rootworms that do not develop on cucurbits but undergo pharmacophagous forays for cucurbitacins are thought to do so to supplement novel host diets that lack these bitter compounds. The ancestral host hypothesis is supported from studies of pyrrolizidine alkaloid pharmacophagy in Lepidoptera but has not been subjected to phylogenetic analysis within the Luperini. New evidence that this feeding behavior is better correlated with an adult affinity for pollen than with larval host offers the possibility that Old and New World rootworm species with an affinity for cucurbitacins converged on this behavior through apomorphic taste receptor modifications (loose receptor hypothesis). Here we test the monophyly of cucurbitacin feeding within the Luperini by using nuclear and mitochondrial sequence data to infer phylogenetic relationships among 49 taxa representing tribes of the Galerucinae and subtribes of the Luperini. The resulting phylogenetic hypothesis is mostly concordant with existing tribal and subtribal delineations within the Subfamily Galerucinae sensu stricto (Galerucinae not including the flea beetles). The establishment of ancestry among the subtribes of the Luperini refutes the monophyly of cucurbitacin feeding and cucurbit specialization, with the New World Diabroticina being paraphyletic to the Old World Aulacophorina and cosmopolitan Luperina. These data unambiguously support the convergent evolution of cucurbitacin feeding in rootworms and are inconsistent with the ancestral host hypothesis.

Animals↗
PubMedDate not supplied

Convergence of experimental multiple Rayleigh matches to peak L- and M-photopigment sensitivity estimates.

Shift in the wavelength of peak sensitivity of the cone photo pigments is a major cause of inter-individual variations in the Rayleigh match. Normal color observers performed multiple Rayleigh matches (i.e., a series of seven Rayleigh-type color matches using various sets of test and primary lights) in order to derive estimates of the M- and L-photo pigment wavelengths of maximum absorbance. We predicted the ratio of incident radiances Pr/Pg for a range of plausible values in terms of wavelength of the peak sensitivity of the M-cone and L-cone. An algorithm allowed us to adjust the values of the peak wavelength of the cone photo pigments in order to minimize the sum of squared differences between predicted and real results of matches. To create candidate M-cone and L-cone photo pigments that best predict the set of equation values, we used the low density spectral absorbance curves of the M-cone and L-cone photo pigments respectively, as tabulated by Stockman and Sharpe (2000), and shifted each template along a logarithmic wavelength scale. For all observers, the system of seven Rayleigh-like equations converges to a unique solution. M- and L-cone photo pigments are estimated separately. The distribution of the wavelength of maximum sensitivity of the photo pigments includes a cluster. Only a few women's results lie outside the cluster. The choice of the template has a considerable influence on the convergence of the algorithm.

Adult↗
PubMed2005

Synthetic strategies of marine polycyclic ethers via intramolecular allylations: linear and convergent approaches.

Strategies for the synthesis of polycyclic ethers based on intramolecular allylations are overviewed. The intramolecular condensation of allylic stannanes and aldehydes is a powerful tool for the synthesis of oxepane derivatives. The reaction is successfully applied to the iterative total synthesis of hemibrevetoxin B (2). Further, the intramolecular allylation of alpha-acetoxy ethers provides an efficient method for the convergent synthesis of polycyclic ethers. The usefulness of the latter strategy is demonstrated in the convergent total synthesis of gambierol (4).

Aldehydes↗
PubMedDate not supplied

Neural networks convergence using physicochemical data.

An investigation of the neural network convergence and prediction based on three optimization algorithms, namely, Levenberg-Marquardt, conjugate gradient, and delta rule, is described. Several simulated neural networks built using the above three algorithms indicated that the Levenberg-Marquardt optimizer implemented as a back-propagation neural network converged faster than the other two algorithms and provides in most of the cases better prediction. These conclusions are based on eight physicochemical data sets, each with a significant number of compounds comparable to that usually used in the QSAR/QSPR modeling. The superiority of the Levenberg-Marquardt algorithm is revealed in terms of functional dependence of the change of the neural network weights with respect to the gradient of the error propagation as well as distribution of the weight values. The prediction of the models is assessed by the error of the validation sets not used in the training process.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Convergent total synthesis of gymnocin-A and evaluation of synthetic analogues.

The first total synthesis of gymnocin-A (1), a cytotoxic polycyclic ether isolated from a notorious red tide dinoflagellate, Karenia mikimotoi, has been accomplished. The synthesis relies heavily on the Suzuki-Miyaura cross-coupling-based methodology to assemble the tetradecacyclic polyether skeleton. Convergent union of the GHI (5) and KLMN (6) rings, both of which were prepared from a common intermediate 7, and the subsequent ring closure of the J ring delivered the GHIJKLMN ring. The crucial coupling between the ABCD and FGHIJKLMN ring fragments (3 and 4, respectively) and stereoselective installation of the C17 hydroxyl group, followed by cyclization of the E ring gave rise to the tetradecacyclic polyether skeleton 2. Finally, incorporation of the 2-methyl-2-butenal side chain completed the total synthesis of gymnocin-A. The convergent nature of the synthesis, which employs three fragments of comparable complexity, is well-suited for preparation of various structural analogues of gymnocin-A to explore the structure-activity relationship. The results of preliminary structure-activity relationship studies of several synthetic analogues are also provided.

Animals↗
PubMed2006

Highly convergent total synthesis of (+)-acutiphycin.

An enantioselective, convergent, total synthesis of (+)-acutiphycin (18 steps, longest linear sequence from commercial materials) features the first application of an alkynyl ether as a macrolactone precursor in total synthesis, as well as the first example of an intermolecular, SmI2-mediated, Reformatsky fragment coupling reaction. The high convergence, efficiency, and modular nature of this synthesis make it amenable to the synthesis of structurally related compounds.

Antineoplastic Agents↗
PubMed2001

Convergent synthesis of noncovalent metallodendrimers containing hydrophobic dendrons at the periphery.

The noncovalent synthesis of "layer-block" metallodendrimers containing hydrophobic shells of covalent dendritic wedges at the periphery is described. Starting from first- and second-generation Fréchet wedges having phosphines at their focal point, convergent dendritic growth yields third- and fourth-generation metallodendrimers in which the coordination of nitriles, pyridines, and phosphines to SCS Pd(II) pincers is used as the assembly motif. In this convergent growth, the number of terminal hydrophobic phosphine wedges increases with generation. The solubility of the dendritic structures in apolar organic solvents such as chloroform and dichloromethane increases accordingly, in contrast to previously reported metallodendrimers. All dendritic structures were characterized by (1)H and (31)P NMR spectroscopy, elemental analysis, and MALDI-TOF mass spectrometry.

Journal Article↗
PubMed2002

Intramolecular radical cyclization-ring-closing metathesis approach to fused polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH ring system of ciguatoxin.

A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the causative toxins for ciguatera fish poisoning, has been developed. The synthesis features convergent coupling to form dioxane acetal, regioselective acetal cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate followed by intramolecular radical cyclization to construct the oxepane ring G, and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1 equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one predominating. This is the first illustration that reproduces the preference for the UP conformer over the DOWN one, which preference was observed for natural ciguatoxins.

Acetals↗
PubMed2002

Approach toward the total synthesis of orevactaene. 2. Convergent and stereoselective synthesis of the C18-C31 domain of orevactaene. Evidence for the relative configuration of the side chain.

The synthesis of the C18-C31 subunit of orevactaene (1) in an enantioselective and convergent manner is reported. Four chiral centers in the structure (i.e., carbons 23, 25, 32, and 33) have unknown configuration; thus, a modular approach has been devised to link the two stereocenter-containing ends of the structure together via a trisubstituted olefin template to ultimately produce all possible diastereomers of the target. Keys to the success of this approach include (i) an efficient synthesis of four diastereomeric hydrophobic tails (C22-C29) of the molecule with two stereogenic centers at C23 and C25; (ii) the synthesis of three stereodefined trisubstituted olefins 37, 38, and 43 using palladium(0)-catalyzed hydrometalation and metallometalation; and (iii) the convergent assembly of the aforementioned sections by a 'one-pot' lithium/halogen exchange, boron/lithium exchange, borate ester saponification, and Suzuki cross-coupling followed by oxidative deprotection. The sequence provided the desired aldehydes 49 and 50 as single isomers in good yields. Compiled spectroscopic data from the literature and present work provides evidence that the relative configuration of the methyl groups in the side chain of orevactaene may be 1,3-syn, which will be confirmed when the total synthesis has been completed. These results have paved the way for a parallel synthesis approach to prepare all 16 possible stereoisomers of orevactaene so that the relative and absolute stereochemistry of this compound can be determined.

Ascomycota↗
PubMed2003

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug.

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-d-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn(Boc)-Pro-OH and H-d-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boc-d-Cha-OH was obtained very efficiently via hydrogenation of d-Phe with PtO(2) in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50-100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Anti-Inflammatory Agents↗
PubMed2004

Mitomycin synthetic studies: stereocontrolled and convergent synthesis of a fully elaborated aziridinomitosane.

Full details of a stereocontrolled and convergent synthetic route to 9a-desmethoxymitomycin A (1) are reported. The target molecule possesses the parent tetrahydropyrrolo[1,2-a]indole ring system characteristic of the mitomycin family of antitumor agents. The synthesis was based on the diastereocontrolled addition of a fully elaborated cinnamylstannane to a pyrrolidine-based N-acyliminium ion as the key convergent step, which resulted in the installation of the C9 and C9a stereogenic centers.

Aziridines↗
PubMed2006

Stereocontrolled and convergent total synthesis of amphidinolide T3.

Stereocontrolled and convergent total synthesis of amphidinolide T3 has been described. A retrosynthetic scheme was constructed that led to the recognition of readily available and enantiomerically related compounds as starting materials for the total synthesis of amphidinolide T3. Thus, the two key building blocks 6 and 7 were defined as subtargets and synthesized in optically active forms. The C1-C12 fragment 6 was derived from commercially available D-glutamic acid or its synthetically equivalent (R)-5-hydroxymethyltetrahydrofuran-2-one 16 as starting material involving highly diastereoselective asymmetric allylation as a key step. The C13-C21 fragment 7 was efficiently synthesized in high yield through the dithiane coupling of the segment 10 and iodide 11, followed by subsequent deprotection and Petasis olefination. Eventually, assembly of the fragment aldehyde 6 and dithiane 7 along with C-C bond formation, a two-step oxidation-reduction sequence, selective macrolactonization, and functional transformation furnished the convergent total and formal synthesis of amphidinolide T3 and T4, and this approach also provides a flexible and practical synthesis of amphidinolide T macrolides.

Glutamic Acid↗
PubMed2006

Convergent and diastereoselective synthesis of the polycyclic pyran core of saudin.

The natural product saudin was found to induce hypoglycemia in mice and, therefore, could be an appealing lead structure for the development of new agents to treat diabetes. A diastereoselective tandem Stille-oxa-electrocyclization reaction has been developed which provides access to the core structure of saudin in a rapid and convergent manner. This new reaction has been extended to the convergent preparation of a series of polycyclic pyran systems. Progress has been made on the advancement of these complex pyran systems toward the natural product. A complete account of these synthetic efforts is presented.

Cyclization↗
PubMed1996

Simple Designs for the Construction of Complex Trans-Fused Polyether Toxin Frameworks. A Convergent Strategy Based on Hydroxy Ketone Cyclization of C-Linked Oxacycles.

A single, unified convergent strategy for the stereocontrolled synthesis of trans-fused polyethers was developed. It was demonstrated that the epimerization and reductive intramolecular coupling of hydroxy ketones in reactions with silane-Lewis acids (SI-LA) to generate ethers in C-linked oxacycles is affected by its conformational preference in a predictable manner. The obtained results make evident that the influence of hydrogen bonding between a hemiketal hydroxyl and a 1,3-diaxial C-O bond is regular and predictable and that convergent synthesis of trans-fused polyethers may confidently be conducted on driving ring closure to oxane rings under thermodynamic conditions

Journal Article↗
PubMed1996

Convergent Synthetic Routes to Orthogonally Fused Conjugated Oligomers Directed toward Molecular Scale Electronic Device Applications.

This paper describes the synthetic organic phase of a project directed toward the construction of molecular scale electronic devices. Outlined is a convergent synthetic route to orthogonally fused conjugated organic oligomers. The final systems are to have a potentially conducting chain fused perpendicularly to a second potentially conducting chain via a sigma bonded network. One of the core segments synthesized is based on a spirobithiophene moiety with a central silicon atom. It is formed by a zirconium-promoted bis(bicyclization) of a tetrapropargylsilane. The second core is a 9,9'-spirobifluorene system. Terminal halide groups provide the linkage points for further extension of the chains via Pd-catalyzed or Pd/Cu-catalyzed cross coupling methods. All four branching arms are affixed to the core in a single operation, thus making the syntheses highly convergent. In the cases of the larger functionalized systems, alkyl substituents on the thiophenes afford soluble materials. In order to prepare the molecules with >50 Å lengths, an iterative divergent/convergent approach had to be utilized for the construction of oligo(thiophene-ethynylene) branching arms. Organopalladium-catalyzed procedures are used extensively for the syntheses of the orthogonally fused compounds.

Journal Article↗
PubMed2005

Entropy convergence in the hydration thermodynamics of n-alcohols.

Using experimental data from the literature, entropy convergence in the hydration thermodynamics of n-alcohols is shown to occur at about 125 degrees C. The phenomenon is reproduced in a more-than-qualitative manner by means of a theoretical approach that accounts for the entropy contributions associated with (a) creation of a cavity in water, (b) turning on solute-water van der Waals interactions, and (c) turning on the solute-water H-bonding potential. The density of water and the effective size of water molecules with their temperature dependence play the pivotal role for the occurrence of entropy convergence, together with the property of the alcohol hydroxyl group to form the same number of H-bonds with water molecules regardless of the length of the alkyl chain.

Alcohols↗