1,720,960 research outputs found
Highly Stereoselective de Novo Synthesis of l-Hexoses
No full textAn efficient and general de novo synthetic route to enantiomerically pure l-hexoses has been accomplished starting from the heterocyclic homologating agent 5,6-dihydro-1,4-dithiin-2-yl[(4-methoxybenzyl)oxy]methane and methyl α,β-isopropylidene-l-glycerate. The sugar scaffold was constructed by an acid-catalyzed domino reaction, which enabled selective preparation of either methyl 2,3-dideoxy-α-l-threo-hex-2-enopyranosides or 1,6-anhydro-2,3-dideoxy-β-l-threo-hex-2-enopyranose as key intermediates. The subsequent double bond functionalization by syn or anti dihydroxylation reactions allowed introduction of the remaining stereogenic centers, leading to desired orthogonally protected l-hexopyranosides with a high degree of diastereoselectivity and with very good overall yields. These and previous results (based on the use of the corresponding l-erythro epimers) contribute to make our approach general and place it among the few methods able to synthesize the whole series of the rare l-hexoses
Domino approach to a novel class of N-ribosyltransferase transition state analogues
No full textN-Ribosyltransferase inhibition represents a target of broad pharmacological relevance, given the crucial role of such enzymes in a number of disease-related events [1]. This is exemplified by the case of Immucillin-H, which picomolar activity has been exploited for diverse therapeutic purposes, e.g. treatment of leukemia, parasite-mediated diseases and autoimmune disorders. Herein a domino approach to the synthesis of novel iminosugar-based nucleoside, analogues of immucilin-H is proposed
Sulfur-assisted domino access to bicyclic dihydrofurans: case study and early synthetic applications
No full textA DDQ-mediated domino reaction (up to six steps in a single process) has been developed to selectively provide substituted dihydrofurans from a common starting material containing a cyclic bis-thioenol ether. Study of the reaction mechanism highlighted a role played by the sulfur-containing moiety in influencing reaction rate and stereoselectivity
Synthesis of 2,3-dihydro-1,4-dithiinyl nucleosides via pummerer-type glycosidation
No full textA straightforward procedure for the preparation of nucleoside analogue 1 and its regioisomer 2 containing a dihydro-1,4-dithiin as sugar moiety has been accomplished in four steps by our readily available heterocyclic system 5. Nucleobase insertion was carried out by direct addition of N4-acetylcytosine to sulfoxide derivatives via Pummerer-type glycosidation reaction
Solid phase synthesis of a novel folate-conjugated 5-aminolevulinic acid methyl ester based photosensitizer for selective photodynamic therapy
No full textThe development of a novel tumor-targeting photosensitizer delivery system, with potential ability to
selectively transport the photosensitizer prodrug 5-aminolevulinic acid methyl ester (MAL) into the
tumor site has been herein described. Conjugation of MAL to folic acid (FA) via an unnatural b-peptide
linker has been carried out almost entirely by an efficient solid phase approach. This molecular system
has been devised for possible applications in selective photodynamic diagnosis (PDD) and therapy (PDT)
Oligonucleotides containing a ribo-configured cyclohexanyl nucleoside: probing the role of sugar conformation in base pairing selectivity
No full textThe synthesis and a preliminary evaluation of the pairing properties of ribo-cyclohexanyl nucleic acids (r-CNA) is herein reported. Incorporation of a single r-CNA nucleotide into natural duplexes did not enhance their stability, while a very high pairing selectivity for RNA was found. As deduced by comparative analysis of Tm and NMR data, a relationship between pairing selectivity and conformational preferences of the “sugar” moiety of r-CNA (and more generally of six-membered nucleic acids) was suggested
Synthesis and Evaluation of Folate-Based Chlorambucil Delivery Systems for Tumor-Targeted Chemotherapy
No full textThe development of tumor-targeting drug delivery systems, able to selectively transport cytotoxic agents into the tumor site by exploiting subtle morphological and physiological differences between healthy and malignant cells, currently stands as one of the most attractive anticancer strategies used to overcome the selectivity problems of conventional chemotherapy. Owing to frequent overexpression of folate receptors (FRs) on the surface of malignant cells, conjugation of cytotoxic agents to folic acid (FA) via suitable linkers have demonstrated to enhance selective drug delivery to the tumor site. Herein, the chemical synthesis and biological evaluation of two novel folate-conjugates bearing the anticancer agent chlorambucil (CLB) tethered to either an aminoether (4,7,10-trioxa-1,13-tridecanediamine) or a pseudo-β-dipeptide (β-Ala-ED-β-Ala) linker is reported. The two drug delivery systems have been prepared in high overall yields (54% and 34%) through straightforward and versatile synthetic routes. Evaluation of cell specificity was examined using three leukemic cell lines, undifferentiated U937 (not overexpressing FRs, FR(-)), TPA-differentiated U937 (overexpressing FRs, FR(+)), and TK6 (FR(+)) cells. Both conjugates exhibited high specificity only to FR(+) cells (particularly TK6), demonstrating comparable antitumor activity to CLB in its free form. These data confirm the reliability of folate-based drug delivery systems for targeted antitumor therapy; likewise, they lay the foundations for the development of other folate-conjugates with antitumor potential
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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