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Chasing a phantom by total synthesis: The butylcycloheptylprodigiosin case

The dispute as to whether “butylcycloheptylprodigiosin” is a natural product or solely a misassigned structure lasted for more than a decade. This open question has now been answered by the first total synthesis of this tripyrrole alkaloid (see picture), which makes explicit use of the peculiarities of its highly strained ortho-anellated nine-membered ring. (Chemical Equation Presented)

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Direct-type vinylogous Mukaiyama-Michael addition reactions involving pyrrolinone donors

The direct Mukaiyama-Michael addition of vinylogous tetramate donors to a number of different Michael acceptors has been easily executed, by employing the TMSOTf/Et3N mixture as soft Lewis acid/base promoter agent. Richly functionalized, highly manipulable gamma-substituted pyrrolinone products were practically synthesized in acceptable to excellent yields, and with diastereoselectivities heavily relying upon the substituent at the nitrogen atom of the pyrrolinone donor.

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Investigations regarding the utility of prodigiosenes to treat leukemia

Prodigiosenes, possessing a 4-methoxypyrrolyldipyrrin skeleton, are known for their anti-cancer activity. Structural modification of the C-ring resulted in a series of prodigiosenes that displayed promising activity against leukemia cell lines during in vitro analysis against the NCI 60 cancer cell line panel. Further in vivo studies of these compounds using the zebrafish model showed persistence of anti-leukemia properties in human K562 chronic myelogenous leukemia cells. The Royal Society of Chemistry.

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PyrrolylBODIPYs: Syntheses, Properties, and Application as Environment-Sensitive Fluorescence Probes

Four pyrrole B-ring-functionalized pyrrolylBODIPYs and their B-ring unsubstituted analogues were synthesized from easily accessible starting 5-halo-2-formylpyrroles and were characterized by nuclear magnetic resonance, high-resolution mass spectrometry, X-ray analysis, and optical/electronic properties. In great contrast to the substitution(s) at the other two pyrrolic units, electron-donating substituent(s) at pyrrole B-ring bring significant blue shift of the absorption and emission bands. Cyclic voltammetry and density functional theory calculations indicate that this blue shift may be attributed to the increased highest occupied molecular orbital and the lowest unoccupied molecular orbital energy levels and the overall increase in the energy band gaps. These pyrrolylBODIPYs generally show intense absorption (centered at 570-624 nm) and fluorescence emission (582-654 nm) in nonpolar solvents. A gradual decrease in the fluorescence intensity was observed for these dyes with the increase in solvent dipolar moment, which combines with the red to far-red absorption/emission, rendering these pyrrolylBODIPYs potential applications as environment-sensitive fluorescence probes as demonstrated in this work for bovine serum albumin.

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Potent and selective PKC inhibitory 5-membered ring analogs of balanol with replacement of the carboxamide moiety

Balanol ((-)-1) is a potent protein kinase inhibitory natural product isolated from the fungus Verticillium balanoides. The lack of cellular activity and protein kinase C selectivity in balanol has prompted a search for analogs that incorporate these properties. This paper describes the synthesis and biological activity of such compounds with substitution similar to balanol, but with a single atom bridge in place of the carboxamide moiety.

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alpha-Pyrrolyl dipyrrins as suitable ligands for coordination chemistry

alpha-Pyrrole substituted dipyrrins (alpha-pyrrolyl dipyrrins) which belong to the family of natural products known as prodigiosins possess potent immunosuppressive, antimicrobial, antimalarial and cytotoxic properties. These tripyrrolic prodigiosin types of systems have attracted attention as versatile ligands for boron and for metals to form complexes which possess interesting properties and biological activity. The pyrrolyl dipyrrin is dianionic and can act as either bidentate or tridentate ligand to form complexes. In this review, we described rational routes to prepare alpha-pyrrolyl dipyrrin ligands and their use in the formation of metal and BF2-complexes. The alpha-pyrrolyl dipyrrins bound to metals either via two dipyrromethene pyrrole nitrogens or using all three pyrrolic nitrogens depending on the type of metal ion. However, the pyrrolyl dipyrrins act as bidentate ligands to form highly fluorescent BF2-complexes of pyrrolyl dipyrrins (3-pyrrolyl BODIPYs). The appended pyrrole ring in 3-pyrrolyl BODIPYs was functionalized with a wide range of functional groups and the functionalized 3-pyrrolyl BODIPYs were subsequently used to construct several novel 3-pyrrolyl BODIPY based fluorescent systems and conjugates. The structural, spectral and electrochemical properties of a variety of 3-pyrrolyl BODIPY based fluorescent systems and their conjugates are discussed in this review.

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Preparation and intramolecular [2+2]-photocycloaddition of 1,5-dihydropyrrol-2-ones and 5,6-dihydro-1H-pyridin-2-ones with C-, N-, and O-linked alkenyl side chains at the 4-position

(Chemical Equation Presented) The 1,5-dihydropyrrol-2-ones 2, 6, 9, and 11 were prepared from methyl tetramates (1a-c), N-Boc-protected tetramic acid (3), or N-Boc-protected tetramic acid bromide (7) in short reaction sequences and in very good overall yields. The homologous 5,6-dihydro-1H-pyridin-2-ones 16,18, 20, 21, 23, and 27 were prepared along analogous routes starting from piperidin-2,4-dione (19) or from its N-terf-butyl derivative 15. Optimized conditions for the [2+2]-photocycloaddition include the use of dichloromethane as the solvent and an irradiation with a mercury low-pressure lamp (lambda = 254 nm). Upon applying these conditions at ambient temperature, the corresponding intramolecular photocycloaddition products 28-37 were obtained in good yields (52-79%) and with perfect diastereoselectivity. The constitution and configuration of the products was elucidated by NMR-spectroscopy. For the O-tethered substrates 2a and 20, a strong decrease of the photocycloaddition rate with temperature was observed. The effect was less pronounced for N- and C-tethered substrates 6, 9, 23, and 27. The use of a chiral complexing agent to achieve enantioselective reactions appears viable. Complexing agent (-)-38, however, is not suited because of its instability at lambda = 254 nm.

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Evaluation of the biosynthetic proposal for the synthesis of marineosins A and B

“Chemical equation presented” The first synthetic efforts toward marlneosins A and B, novel spiroaminals from a Streptomyces actinomycete, are described by evaluation of the proposed biosynthesis. The hypothesized biosynthetlc C1-C25 Diels-Alder substrate was prepared In 8 steps in 5.1% overall yield; however, the proposed biomimetic inverse-electron-demand hetero-Diels-Alder reaction failed to deliver the marineosin core. Molecular mechanics supports this observation.

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New Protocols for the Synthesis of Substituted 4-O-Methyl Tetramates

The deprotonation behaviour of 4-methoxypyrrol-2(5H)-ones (4-O-methyl tetramates) is defined and exploited to provide methods for the synthesis of methyl tetramates variously substituted at N-1, C-5, and C-3.

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A ratiometric fluorescent pH glass optode based on a boron-dipyrromethene derivative

This paper describes the preparation of a single-excitation, dual-emission type optical pH-sensing device using a newly designed proton-responsive boron-dipyrromethene derivative (KBH-01). The indicator dye was successfully synthesized and immobilized covalently on the surface of a porous glass support (Corning 7930, 13 mm ¡Á 30 mm size with a thickness of 1 mm) having a large internal surface area (250 m2/g) using a silane-coupling agent. The resulting pH glass optode shows dual fluorescence emission in aqueous buffer solutions of varying pH values, allowing ratiometric signal processing. The response curves are independent of buffer ionic strength. The sensor response was found to be reversible in the pH range from below 0.8 to 4.5 and showed good repeatability. The determination of pH of gastric juice samples was demonstrated as a possible practical application of the pH glass optode. The pH values determined by the pH glass optode corresponded reasonably to those measured by a field effect transistor (FET) pH meter. These results indicate that the novel pH glass optode can be employed as a pH-sensing device with high durability, sensitivity and accuracy for medical and environmental analyses.

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