An indole-containing dauer pheromone component with unusual dauer inhibitory activity at higher concentrations

In Caenorhabdltls elegans, the dauer pheromone, which consists of a number of derivatives of the 3,6-dideoxysugar ascarylose, is the primary cue for entry into the stress-resistant, nonaging dauer larval stage. Here, using activity-guided fractionation and NMR-based structure elucidation, a structurally novel, indole-3-carboxyl-modified ascaroside is identified that promotes dauer formation at low nanomolar concentrations but inhibits dauer formation at higher concentrations. © 2009 American Chemical Society

A Novel ascaroside controls the parasitic life cycle of the entomopathogenic nematode heterorhabditis bacteriophora

Entomopathogenic nematodes survive in the soil as stress-resistant infective juveniles that seek out and infect insect hosts. Upon sensing internal host cues, the infective juveniles regurgitate bacterial pathogens from their gut that ultimately kill the host. Inside the host, the nematode develops into a reproductive adult and multiplies until unknown cues trigger the accumulation of infective juveniles. Here, we show that the entomopathogenic nematode Heterorhabditis bacteriophora uses a small-molecule pheromone to control infective juvenile development. The pheromone is structurally related to the dauer pheromone ascarosides that the free-living nematode Caenorhabditis elegans uses to control its development. However, none of the C. elegans ascarosides are effective in H. bacteriophora, suggesting that there is a high degree of species specificity. Our report is the first to show that ascarosides are important regulators of development in a parasitic nematode species. An understanding of chemical signaling in parasitic nematodes may enable the development of chemical tools to control these species. © 2012 American Chemical Society

Approaches for Sample Characterization and Lithography with Nanoparticles using Modes of Scanning Probe Microscopy

Measurement and imaging modes of scanning probe microscopy (SPM) have been routinely applied for characterizing systems of nanoparticles; however the evolution of fabrication methods to prepare arrangements of nanoparticles remains a challenge. Reproducible fabrication of surface structures which integrate nanoparticles within ultra-small patterns will require innovative approaches to achieve high throughput and precision. Strategies for nanoscale lithography have been introduced for preparing defined arrangements of nanoparticles on surfaces based on physical or chemical interactions. For example, physisorption was employed for attaching nanoparticles based on colloidal lithography and site-directed assembly. Microfabricated atomic force microscope (AFM) tips with capillary channels have been used to pattern nanoparticles through electrostatic interactions. Specific chemical interactions can be designed for patterning nanoparticles with dip-pen nanolithography and SPM-based fabrication. Studies with nanoparticles are reviewed, which have applied either in situ and ex situ approaches for imaging and measurements using modes of SPM. The imaging principle for contact and tapping modes are described with example studies of nanoparticle patterns. The SPM modes for measuring physical properties (e.g. magnetism, softness, conductance) using force modulation microscopy (FMM), magnetic force microscopy (MFM), magnetic sample modulation (MSM), and conductive probe AFM are described for selected studies of lithography with nanoparticles. Strategies for patterning nanoparticles using lithography modes of nanoshaving, dip-pen nanolithography, and tip-induced oxidation have been reported for a range of nanoparticle systems. Applications for nanotechnology will require the integration of nanoparticles within engineered surface architectures. Stable, organized arrangements of nanoparticles with robust chemical/physical attachment to surfaces will be needed for applications, to fully gain advantages of the characteristic quantum properties of nanoparticles

Application of visible-light photosensitization to form alkyl-radical-derived thin films on gold

Visible-light irradiation of phthalimide esters in the presence of the photosensitizer [Ru(bpy)3]2+ and the stoichiometric reducing agent benzyl nicotinamide results in the formation of alkyl radicals under mild conditions. This approach to radical generation has proven useful for the synthesis of small organic molecules. Herein, we demonstrate for the first time the visible-light photosensitized deposition of robust alkyl thin films on Au surfaces using phthalimide esters as the alkyl radical precursors. In particular, we combine visible-light photosensitization with particle lithography to produce nanostructured thin films, the thickness of which can be measured easily using AFM cursor profiles. Analysis with AFM demonstrated that the films are robust and resistant to mechanical force while contact angle goniometry suggests a multilayered and disordered film structure. Analysis with IRRAS, XPS, and TOF SIMS provides further insights

1. Synthesis and biological evaluation of Manzamine analogs. 2. Applications of the intramolecular crossed [2+2] photocycloaddition of vinylogous amides with olefins

This dissertation describes two independent research projects. The first part discusses the synthesis and biological evaluation of four compounds based on the structure of Manzamine A. The parent structure Manzamine A has been shown to have both in vitro and in vivo activity against the malaria-causing pathogen Plasmodium falciparum . Because of the complexity and limited availability of Manzamine A, we set out to synthesize and evaluate four analogs as the initial effort in an ongoing project to develop a structure-activity relationship (SAR) for the antimalarial activity of Manzamine A. The analogs were synthesized via the Suzuki coupling of 1-bromo-β-carboline and the appropriate boronate esters. The boronate esters were synthesized by short and straightforward syntheses. Biological screening of the B, BC and AB ring system analogs of Manzamine A against P. falciparum showed greatly attenuated activity relative to Manzamine A, suggesting that more complex analogs would be necessary to approach the activity of the parent structure.* The second part of this dissertation describes the development of the intramolecular crossed [2+2] photocycloaddition of vinylogous amides with olefins. We set out to synthesize a photosubstrate which, upon irradiation, would provide a photoproduct that could be elaborated to the structure of the naturally-occurring alkaloid peduncularine. Initial efforts at synthesizing a model system were directed toward photosubstrates with allene coupling partners. Later efforts involved the use of allene surrogates of varying complexity. A rationale for the stereochemical outcome of the photocycloaddition is presented. A solution to a stereochemical problem incurred during the course of these studies exploiting the pseudosymmetry of derived photoproducts is also presented.* *Please refer to dissertation for diagrams

MPTGs: Thioglycoside Donors for Acid-Catalyzed O-Glycosylation and Latent-Active Synthetic Strategies

© 2019 American Chemical Society. 4-(p-Methoxyphenyl)-4-pentenylthioglycosides (MPTGs) undergo acid-catalyzed O-glycosylation with a range of alcohol acceptors in the presence of 10 mol % of triflic acid at room temperature. Particularly encouraging is the reactivity of MPTGs toward unreactive acceptors. MPTGs can be synthesized from the requisite vinyl bromides using the Suzuki reaction, and this chemistry can be leveraged toward a latent-active strategy for oligosaccharide synthesis

Total Synthesis of an All-1,2--Linked Repeating Unit from the D78 Capsular Polysaccharide

Chemical synthetic efforts have resulted in the preparation of the assigned tetrasaccharide repeating subunit from the KL4-associated capsular polysaccharide. A convergent synthetic strategy hinging on a 1,2--selective [2+2] glycosylation to generate the fully protected tetrasaccharide was key to the success of this synthesis

Pseudosymmetry in azabicyclo[2.1.1]hexanes. A stereoselective construction of the bicyclic core of peduncularine

Intramolecular photocycloaddition of 41 or its equivalent leads to the formation of photoadduct 25. While retro-Mannich fragmentation of the b bond in 25 leads to the formation of 44 (via 43), with the incorrect relative stereochemistry for the synthesis of peduncularine 5, selective fragmentation of the a bond in 25 leads to the formation of 42 (via 26) with the correct relative stereochemistry for the synthesis of 5. © 2006 American Chemical Society

Intramolecular Photoaddition of Vinylogous Amides with Allenes: A Novel Approach to the Synthesis of Pyrroles.

Irradiation of vinylogous amide or imide 5 (R = H, alkyl, or Ac) leads to the selective formation of either crossed photoadduct 7 (R = Ac) or parallel photoadduct 8 (R = H or alkyl) as a function of the nature of the group R. The latter result leads to a novel approach to the synthesis of pyrroles, that is, 8′. © 2006 American Chemical Society