Total Synthesis and Structural Reassignment of the Molt-Inhibiting Marine Alkaloid Erebusinone.

The marine alkaloid erebusinone is a secondary metabolite isolated from the Antarctic sponge . Initial biological assays have shown that erebusinone increases amphipod mortality, probably by inhibition of the biosynthesis of molting hormone (ecdysone). Herein, we report the first total synthesis of the proposed structure of erebusinone and a structural revision.

Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids.

Two novel pyrroloiminoquinone alkaloids, 6-chlorodamirone A and 6-bromodamirone A, have been identified for the first time from the marine sponge sp. (order: Poecilosclerida: family Latrunculiidae), sourced from Western Australia. Alongside these new compounds, seven previously known metabolites were also isolated.

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

Background: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects.

An Orthogonal Conductance Pathway in Spiropyrans for Well-Defined Electrosteric Switching Single-Molecule Junctions.

While a multitude of studies have appeared touting the use of molecules as electronic components, the design of molecular switches is crucial for the next steps in molecular electronics. In this work, single-molecule devices incorporating spiropyrans, made using break junction techniques, are described. Linear spiropyrans with electrode-contacting groups linked by alkynyl spacers to both the indoline and chromenone moieties have previously provided very low conductance values, and removing the alkynyl spacer has resulted in a total loss of conductance.

Multistate Switching of Some Ruthenium Alkynyl and Vinyl Spiropyran Complexes.

To study the switching properties of photochromes, we undertook the synthesis and characterization of several ruthenium organometallic complexes of the type [Ru(Cp*)(dppe)(C≡C-SP)] or [Ru(CO)(dppe)(PPh)Cl(CH═CH-SP)], where SP = spiropyran. The spectroscopic and electrochemical properties of the complexes were determined by careful cyclic voltammetric and spectroelectrochemical experiments. Whereas the mononuclear alkynyl ruthenium complexes undergo one-electron oxidations localized over the metal alkynyl moiety, the oxidation of the mononuclear vinyl ruthenium complexes is centered on the indoline moiety of the spiropyran.

Synthesis, Characterization, and Bioactivity of the Lichen Pigments Pulvinamide, Rhizocarpic Acid, and Epanorin and Congeners.

The lichen natural products pulvinamide, rhizocarpic acid, and epanorin have been synthesized and characterized spectroscopically and by X-ray crystallography. The syntheses, by ring-opening of pulvinic acid dilactone (PAD), may well be biomimetic, given the well-known occurrence of PAD in lichen. The enantiomers, -rhizocarpic acid and -epanorin, and corresponding carboxylic acids, norrhizocarpic acid and norepanorin, were similarly prepared.

Multifunctional switching properties of "wire-like" dinuclear ruthenium bis-alkynyl spiropyran complexes.

Multifunctional switches are crucial to the development of smart molecular materials and molecular-electronic applications. Here, we describe the synthesis, structure, and characterization of several spiropyrans functionalized with alkynyl-[Ru(dppe)] moieties. Through electrochemical and spectroelectrochemical studies, we demonstrate access to several stable redox states, in addition to states accessed acidochromism and photoisomerisation.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described.

Toward the Total Synthesis of Alpkinidine: Michael Addition to Isoquinolinetrione CE Ring-System Synthons.

Strategies toward the total synthesis of the marine pyrroloacridine alkaloid alpkinidine have been explored, focusing on linking quinonoid CE ring-system synthons with the A ring, followed by condensation to form the B and D rings. The key Michael addition of the ester enolate derived from ethyl -nitrophenylacetate to 2-methylisoquinoline-1,5,8(2)-trione proceeded with the wrong regiochemistry. This issue was addressed by incorporating the D-ring nitrogen at an earlier stage, affording advanced intermediates possessing the complete carbon skeleton of alpkinidine.

Toward the Total Synthesis of Alpkinidine: Synthesis of Haloquinone CE Ring System Synthons and Attempted Nucleophilic Bisannulation.

Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl -nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl -nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2)-trione, required to extend the model strategy to alpkinidine, was unfruitful, giving only complex mixtures. Efforts to direct the regiochemistry of the key Michael substitution step using 6-bromo-2-methylisoquinoline-1,5,8(2)-trione afforded an adduct sharing the complete carbon skeleton of alpkinidine, but this could not be elaborated to the natural product.

PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth.

Isotope-Coded Maleimide Affinity Tags for Proteomics Applications.

Isotope-coded affinity tags (ICATs) are valuable tools for mass spectrometry-based quantitative proteomics, in particular, for comparison of protein (cysteine-residue) thiol oxidation state in normal, stressed, and diseased tissue. However, the iodoacetamido electrophile used in most commercial ICATs suffers from poor thiol-selectivity and modest rates of adduct formation, which can lead to spurious results. Hence, we designed and synthesized three ICATs containing thiol-selective -alkylmaleimide electrophiles (isotope-coded maleimide affinity tags = ICMATs) and assessed these as mass spectrometry probes for ratiometric analysis of lysozyme and muscle proteomes.

Total Synthesis of the Antitumor-Antitubercular 2,6'-Bijuglone Natural Product Diospyrin and Its 3,6'-Isomer.

The 2,6'-bijuglone natural product diospyrin and its unnatural 3,6'-isomer idospyrin have been synthesized in seven steps each from ,-diethylsenecioamide in overall yields of 12% and 13%, respectively. The syntheses diverge from ramentaceone (7-methyljuglone) and include a key Suzuki-Miyaura cross-coupling. Diospyrin, idospyrin, and several synthetic precursors exhibit potent and selective cytotoxicity to the murine myeloma NS-1 cell line over neonatal foreskin cells.

Discovery of Potent -Ethylurea Pyrazole Derivatives as Dual Inhibitors of and .

() and () are causative agents of parasitic diseases known as human African trypanosomiasis and Chagas disease, respectively. Together, these diseases affect 68 million people around the world. Current treatments are unsatisfactory, frequently associated with intolerable side-effects, and generally inadequate in treating all stages of disease.

The chemical and ultra-structural analysis of thin plastic films used for surgical attenuation of portosystemic shunts in dogs and cats.

The objective of the study was to (1) characterize and compare the chemical composition at the surface, subsurface and in the bulk of thin plastic films used for portosystemic shunt attenuation in their native state and after plasma exposure. (2) Assess the presence, concentration and location of irritant compounds (e.g dicetyl phosphate) within the films.

Chemically and Mechanically Controlled Single-Molecule Switches Using Spiropyrans.

Developing molecular circuits that can function as the active components in electrical devices is an ongoing challenge in molecular electronics. It demands mechanical stability of the single-molecule circuit while simultaneously being responsive to external stimuli mimicking the operation of conventional electronic components. Here, we report single-molecule circuits based on spiropyran derivatives that respond electrically to chemical and mechanical stimuli.

Total Synthesis of the Antimalarial Ascidian Natural Product Albopunctatone.

The first approaches to the 10'-anthronyl-2-anthraquinone skeleton have been devised, allowing two syntheses of the marine natural product albopunctatone. Both routes involve regioselective addition of a nucleophilic masked anthraquinone to a protected chrysazin derivative; the best affords albopunctatone in five steps and 35% overall yield. Albopunctatone exhibits potent inhibitory activity against and negligible toxicity to a range of other microbial pathogens and mammalian cells.

Carbon-Rich Trinuclear Octamethylferrocenophanes.

Several trinuclear ferrocenes are obtained by Friedel-Crafts reaction of octamethylferrocene with ferrocenoyl chloride and subsequent modifications. 1,1'-Diferrocenoyloctamethylferrocene (3) is transformed to the divinyl derivative (4a) by reaction with MeLi and AlCl. The reactive 4a cyclizes spontaneously to a [4]ferrocenophane with buta-1,3-diene handle (5) or in the presence of AlCl to a [3]ferrocenophane with propene handle (6).

Changes in chemical and ultrastructural composition of ameroid constrictors following in vitro expansion.

Objective: To (1) characterise the chemical and ultra-structural composition of ameroid constrictors, at a native state and during in vitro expansion and (2) determine the presence of irritant compounds at the surface or within the bulk of the constrictor.

Methods: Twelve sterile, commercially packaged ameroid constrictors (3 repeats of 3.5 mm, 5 mm, 6 mm and 7 mm internal diameter) were analysed by time-of-flight secondary ion mass spectrometry, Raman spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy and scanning electron microscopy.

Confirmation of the Revised Structure of Samoquasine A and a Proposed Structural Revision of Cherimoline.

The identity of the natural product samoquasine A has remained obscure since its isolation from custard apple seeds in 2000. One of the proposed structures, benzo[ f]phthalazin-4(3 H)-one, was prepared in two steps by regioselective ortho-lithiation/formylation of N, N-diisopropyl-2-naphthylamide, followed by cyclization with hydrazine, but was shown to be different from the natural product. Perlolidine, another candidate structure, was synthesized by a novel route involving a β-selective Heck reaction of butyl vinyl ether.

Reprint of: Antiproliferative activity of the Antrodia camphorata secondary metabolite 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole and analogues.

Both the traditional Chinese medicinal fungus, Antrodia camphorata, and its secondary metabolite, 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole, have been reported to possess promising anticancer activity. In this work the natural product and analogues bearing more polar substituents were synthesised and assessed for antiproliferative activity in the NCI-60 screen. Although each compound inhibited the growth of some cell lines at 10μM, none had sufficient activity to warrant further investigation.

Antiproliferative activity of the Antrodia camphorata secondary metabolite 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole and analogues.

Both the traditional Chinese medicinal fungus, Antrodia camphorata, and its secondary metabolite, 4,7-dimethoxy-5-methylbenzo[d][1,3]dioxole, have been reported to possess promising anticancer activity. In this work the natural product and analogues bearing more polar substituents were synthesised and assessed for antiproliferative activity in the NCI-60 screen. Although each compound inhibited the growth of some cell lines at 10μM, none had sufficient activity to warrant further investigation.

Control over cyclisation sequences of 1,1'-bifunctional octamethylferrocenes to ferrocenophanes.

This paper describes the facile synthesis of a number of electron rich octamethyl[1.4]ferrocenophanes with unsaturated handles from 1,1'-bis(1-chlorovinyl)octamethylferrocene. Treatment of this reactive compound with sodium hydroxide in DMF initiates a series of reactions resulting in the formation of four different ferrocenophanes.

What Is the Structure of the Antitubercular Natural Product Eucapsitrione?

1,5,7-Trihydroxy-6H-indeno[1,2-b]anthracene-6,11,13-trione (1), proposed to be the antitubercular natural product eucapsitrione, has been synthesized in 43% overall yield and six steps, including a key Suzuki-Miyaura biaryl coupling and a directed remote metalation (DReM)-initiated cyclization. The physical and spectroscopic properties of 1 do not match the data reported for the natural product. At this time there is insufficient information available to enable a structure reassignment.

Focus on O-phosphohydroxylysine, O-phosphohydroxyproline, N -phosphotryptophan and S-phosphocysteine.

The synthesis and chemistry of the lesser-known phosphoamino acids, O-phosphohydroxylysine, O-phosphohydroxyproline, N -phosphotryptophan and S-phosphocysteine are described in detail. In addition, where anything at all is known, the biological synthesis, occurrence and functions of these phosphoamino acids are described. Of these phosphoamino acids, only N -phosphotryptophan has not been reported to occur in proteins; however, apart from the roles of S-phosphocysteine in the sugar transporter component (EII) and in catalysis by protein phosphotyrosine phosphatase, little is currently known about the biological roles of the phosphoamino acids when they occur as post-translational modifications.