46 research outputs found

    Fluorenylidene-pyrroline Biomimetic Light-driven Molecular Switches

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    A new family of biomimetic photoactivated molecular switches based in the retinal chromophore is described. Expedient synthesis allows a library of compounds with a different substitution pattern, including chiral substituents, to be obtained. The effect of substitution, solvent, and light source on the photoisomerization step has been assessed. The absorption maximum has been red-shifted ca. 50 nm with respect to related systems and rotation is now easily achieved by using visible light

    Toward A Stable Alpha-cycloalkyl Amino Acid With A Photoswitchable Cationic Side Chain

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    The N-alkylated indanylidenepyrroline (NAIP) Schiff base 3 is an unnatural a-amino acid precursor potentially useful for the preparation of semisynthetic peptides and proteins incorporating charged side chains whose structure can be modulated via Z/E photoisomerization. Here we report that the heteroallylic protons of 3 led to partial loss of ethanol accompanied by formation of the novel heterocyclic system 4 during attempted deprotection. We also show that the same protons catalyze the thermal isomerization of 3, making the light-driven conformational control concept ineffective for times longer than a few hours. These problems are not present in the previously unreported compound 5 where the acidic methyl group is replaced by an H atom. Therefore, 5, rather than 3, constitutes a promising prototype for the design of building blocks capable to modulate the electrostatic potential of a protein in specific locations via light irradiation

    Design and synthesis of99mTcN-labeled dextran-mannose derivatives for sentinel lymph node detection

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    Background: New approaches based on the receptor-targeted molecular interaction have been recently developed with the aim to investigate specific probes for sentinel lymph nodes. In particular, the mannose receptors expressed by lymph node macrophages became an attractive target and different multifunctional mannose derivate ligands for the labeling with99mTc have been developed. In this study, we report the synthesis of a specific class of dextran-based, macromolecular, multifunctional ligands specially designed for labeling with the highly stable [99mTc≡N]2+core. Methods: The ligands have been obtained by appending to a macromolecular dextran scaffold pendant arms bearing a chelating moiety for the metallic group and a mannosyl residue for allowing the interaction of the resulting macromolecular99mTc conjugate with specific receptors on the external membrane of macrophages. Two different chelating systems have been selected, S-methyl dithiocarbazate [H2N-NH-C(=S)SCH3=HDTCZ] and a sequence of two cysteine residues, that in combination with a monophosphine coligand, are able to bind the [99mTc≡N]2+core. Conclusions: High-specific-activity labeling has been obtained by simple mixing and heating of the [99mTc≡N]2+group with the new mannose-dextran derivatives

    Synthesis and NLRP3-Inflammasome Inhibitory Activity of the Naturally Occurring Velutone F and of Its Non-Natural Regioisomeric Chalconoids

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    Plant-derived remedies rich in chalcone-based compounds have been known for centuries in the treatment of specific diseases, and nowadays, the fascinating chalcone framework is considered a useful and, above all, abundant natural chemotype. Velutone F, a new chalconoid from Millettia velutina, exhibits a potent effect as an NLRP3-inflammasome inhibitor; the search for new natural/non-natural lead compounds as NLRP3 inhibitors is a current topical subject in medicinal chemistry. The details of our work toward the synthesis of velutone F and the unknown non-natural regioisomers are herein reported. We used different synthetic strategies both for the construction of the distinctive benzofuran nucleus (BF) and for the key phenylpropenone system (PhP). Importantly, we have disclosed a facile entry to the velutone F via synthetic routes that can also be useful for preparing non-natural analogs, a prerequisite for extensive SAR studies on the new flavonoid class of NLRP3-inhibitors

    Sometimes, the Least Demanding Solution Is the Most Suitable: A Careful Survey of NMR Spectra of a Phosphonium Salt Accounted for Its “Unusual Wittig Reaction”

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    Careful product analysis in combination with appropriate supporting experiments unambiguously proves that in contrast to what was previously reported, generation of the phosphonium salt from a ÎČ- cyclocitral-derived allylic alcohol and PPh3HBr takes place via a protondriven elimination/addition path

    Recent Developments in General Methodologies for the Synthesis of α‑Ketoamides

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    The α-ketoamide motif is widely found in many natural products and drug candidates with relevant biological activities. Furthermore, α-ketoamides are attractive candidates to synthetic chemists due to the ability of the motif to access a wide range of functional group transformations, including multiple bond-forming processes. For these reasons, a vast array of synthetic procedures for the preparation of α- ketoamides have been developed over the past decades, and the search for expeditious and efficient protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged since the 1990s up to the present. The different synthetic routes have been grouped according to the way the α-ketoamide moiety has been created. Thus, syntheses of α-ketoamides proceeding via C(2)- oxidation of amide starting compounds are detailed, as are amidation approaches installing the α-ketoamide residue through C(1)−N bond formation. Also discussed are the methodologies centered on C(1)−C(2) σ-bond construction and C(2)−R/Ar bond-forming processes. Finally, the literature regarding the synthesis of α-ketoamide compounds by palladium-catalyzed double-carbonylative amination reactions is discussed

    A convenient synthesis of λ-oxo-acrylates

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    Ethyl 2,4-dioxoalkanoates react chemoselectively with pyrrolidine acetate at the more electrophilic C-2 carbonyl, producing enaminone esters which on reduction with NaCNBH4 followed by pyrrolidine elimination, were transformed into γ-oxo-acrylates. © 1988

    Hagemann's ester: a timeless building block for natural product synthesis

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    none4The potential of Hagemann’s ester as a building block in the synthesis of complex and biologically active natural products is the topic of this report. Hagemann’s ester chemical transformations allowed the development of diverse and creative applications frequently entailing a wide range of new and modern chemistry. The collected material, covering the development of its chemistry from the very beginning up to the present time, has been organized in sections where the papers listed are discussed in chronological order. Sections 1 and 2 are dedicated to a short introduction and to a description of the different preparations of Hagemann’s ester. The alkylation of the vinylogous beta-keto ester system, the most common operation on the starting ester, has been discussed in detail in Section 3. Synthetic applications involving chemical modifications of the ester functionality, namely removal, preservation and elaboration, have been considered in Sections 4–6, while syntheses featuring Hagemann’s ester fragmentation into linear carbon chains are collected in Section 7. Finally, Section 8 has been dedicated to the preparation and synthetic applications of optically active Hagemann’s ester derivatives. For the sake of clarity, the carbon-atom fragments of the different synthetic targets coming from Hagemann’s ester or its analogues are marked in red.noneG.P. Pollini; S. Benetti; C. De Risi; V. ZaniratoPollini, Gian Piero; Benetti, Simonetta; DE RISI, Carmela; Zanirato, Vinici

    Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

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    A study was conducted to demonstrate synthetic routes to chiral nonracemic and racemic dihydro- and tetrahydrothiophenes. The study presented a comprehensive survey of the methods available for the asymmetric synthesis of dihydro- and tetrahydrothiophene compounds with chirality at carbon. The synthetic routes to chiral nonracemic dihydro- and tetrahydrothiophenes were divided according to the way the asymmetry was introduced. The asymmetric synthesis of dihydro- and tetrahydrothiophenes represented an emerging area in organic synthesis. Chiral nonracemic dihydro- and tetrahydrothiophenes were obtained either from chiral auxiliaries and chiral synthons or by application of organocatalytic and desymmetrization processes. The use of chiral auxiliaries for the preparation of enantiomerically pure compounds had found wide applications for a variety of reactions

    Synthesis and evaluation of the antifungal activity of a new class of N-acylureas.

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    none5Four series of N-​acylureas were synthesized and evaluated against phytopathogenic fungi. Activity against Pythium irregulare in vitro was mostly limited to compds. with R = Pr or iso-​Pr. None of the compds. was effective against downy mildew (Sphaerotheca fulginea) of cucumber.noneP. BARALDI; GUARNERI M.; MANFREDINI S.; SIMONI D.; ZANIRATO V.Baraldi, Pier Giovanni; Guarneri, Mario; Manfredini, Stefano; Simoni, Daniele; Zanirato, Vinici
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