RESUMEN
Construction of protected 2,3-dideoxy-2-fluoro-2,3-endo-methylene-pentofuranoses from d-glyceraldehyde and 2,3-dideoxy-2-fluoro-3-C-hydroxymethyl-2,3-endo-methylene-pentofuranoses from d-isoascorbic acid, via Simmons-Smith-type stereoselective cyclopropanations on the respective fluoroallyl alcohols, is described. Synthesis of the corresponding conformationally locked sugar modified uridine and guanosine nucleosides was achieved via Vorbrüggen or Mitsunobu methodologies. Stereochemical confirmation of the novel nucleosides was performed on the basis of 2D NOESY NMR experiments. Analysis of 2',3'-dideoxy-2'-fluoro-3'-C-hydroxymethyl-2',3'-endo-methylene-uridine by X-ray crystallography yielded the principal conformational parameters and indicated that the furanoid ring adopted an (o)E/(o)T1, East pucker. The uridine and guanosine nucleosides were found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay, which was corroborated on examination of the corresponding nucleoside triphosphates against the HCV NS5B polymerase.
RESUMEN
The synthesis of the novel 2',3'-cyclopropane nucleoside 3'-deoxy-3'-C-hydroxymethyl-2',3'-methylene-uridine is described. Stereoselective construction of the cyclopropane ring was achieved via Simmons-Smith cyclopropanation of a benzyl protected silyl enol ether, which was itself derived from 1,2-O-isopropylidene-α-D-xylofuranose.
Asunto(s)
Ciclopropanos/química , Uridina , Estructura Molecular , Monosacáridos/química , Estereoisomerismo , Uridina/análogos & derivados , Uridina/síntesis química , Uridina/química , Uridina/farmacologíaRESUMEN
An efficient synthesis of NP25302 is presented that relies on 5-endo-dig N-cyclization to establish the bicyclic core and Curtius rearrangement to install the N-acyl vinylogous urea functionality.
Asunto(s)
Alcaloides de Pirrolicidina/síntesis química , Ciclización , Modelos Moleculares , Estructura Molecular , Urea/química , Compuestos de Vinilo/químicaRESUMEN
This study investigated the value of antemortem (AM) and postmortem (PM) radiographs of the claviculae and C3-T4 vertebrae to identify skeletons of missing U.S. soldiers from past military operations. In total, 12 field-recovered skeletons and AM chest radiographs of 1460 individuals were used. For each skeleton, examiners analyzed an array of AM chest radiographs (up to 1000 individuals) and attempted to identify the correct PM/AM radiographic match. When examiners were able to compare all images within a single test, only true-positive identifications were made. When AM radiographs were presented one-at-a-time, in sequential order, and without examiners having knowledge of array size, erroneous identifications resulted but they were almost exclusively made by untrained examiners (accuracy = 35% vs. 90% for trained examiners). This study demonstrates the value of chest radiographs for the identification of disarticulated and even eroded skeletons, but only when methods are wielded by trained examiners.
Asunto(s)
Vértebras Cervicales/diagnóstico por imagen , Clavícula/diagnóstico por imagen , Radiografía Torácica , Vértebras Torácicas/diagnóstico por imagen , Adulto , Antropología Forense , Humanos , Masculino , Personal Militar , Variaciones Dependientes del Observador , Competencia Profesional , Estados UnidosRESUMEN
Silatropic carbonyl ene cyclisations of beta-(allylsilyloxy)- and beta-(crotylsilyloxy)butyraldehydes are shown to proceed with high stereoselectivity but at a much reduced rate in comparison to the cyclisation of analogous alpha-substrates. In the second section, olefin cross-metathesis is explored as a route to substituted alpha-(allylsilyloxy)aldehydes and the method applied to the synthesis of diastereomeric 2-deoxy- and 2-deoxy-2-C-phenyl hexose derivatives from butanediacetal-protected D-glyceraldehyde.
Asunto(s)
Aldehídos/química , Alquenos/química , Hexosas/síntesis química , Compuestos de Organosilicio/química , Silicio/química , Ciclización , Hexosas/químicaRESUMEN
X-ray crystallography was used to confirm the structure of the enantio-enriched title compound, C(10)H(12)Cl(2)O, a bicylic enol ether. A bridged boat-like structure is adopted and the dichloro-methyl-ene C atom is positioned significantly removed from the core bicyclic unit. In the crystal structure, mol-ecules pack to form sheets approximately perpendicular to the a and c axes.