Synthesis of perfluorinated allylic compounds by radical allylation and their purification over fluorous reverse-phase silica

A simple free-radical method for the preparation of a variety of perfluorinated allylic compounds has been developed starting from perfluoroalkyl iodides and allyltins. Allyltributyltin, methallyltributyltin and crotyltributyltin all proved to be useful for the transformation. The desired perfluorinated allylic compound was conveniently isolated from the crude mixture by solid-phase extraction with fluorous reverse-phase silica (FRPS). © 2001 Elsevier Science Ltd

[18F]Amylovis as a potential PET probe for β-Amyloid plaque: synthesis, in silico, in vitro and in vivo evaluations

[Background] Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. [Methods] Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/Aß plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. [Results] The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the Aβ-peptide, mainly through π-π interactions. According to a dynamic simulation study the ligand-Aβ peptide complexes are stable in simulation-time (ΔG = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to Aβ plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11±0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. [Conclusion] The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of Aβ senile plaques.This project was sponsored by Fondo Financiero de Ciencia e Innovación (FONCI) of Ministry of Science, Technology and Environment of Cuba (CITMA) Also, the present work was supported by the project I-LINK+ 0965 of the Consejo Superior de Investigaciones Científicas, Spain, and Cuba's National Science and Technology Program (PNCT, 31200).Peer reviewe

Polymer networks assembled by host-guest inclusion between adamantyl and beta-cyclodextrin substituents on poly(acrylic acid) in aqueous Solution

Polymer networks have been constructed through host−guest inclusion between β-cyclodextrin (β-CD) and 1-(2-aminoethyl)amidoadmantyl (ADen) substituents on poly(acrylic acid) (PAA). The structure of the networks and the host−guest interactions between the β-CD and ADen groups were studied by rheology and 2D 1H NOESY NMR spectroscopy. The maximum viscosity of the mixture of β-CD substituted PAA (β-CDPAA) and ADen substituted PAA (ADenPAA) occurred at a 1:1 β-CD:ADen substituent ratio which confirmed their binary inclusion. The viscosity of the mixture of the two polymers decreased upon addition of native β-CD due to its ability to compete favorably with the β-CD substituents of β-CDPAA in the inclusion of the ADen substituents of ADenPAA and the consequent disintegration of the polymer network. The rheological properties of the polymer networks were temperature sensitive. In the temperature range 10−35 °C, the storage modulus and the loss modulus obeyed a time−temperature superposition. The horizontal and vertical temperature shift factors, aT and bT, obeyed a simple Arrhenius relationship for which the activation energies were found to be 70.3 ± 0.4 and −2.2 ± 0.1 kJ mol−1, respectively. 2D 1H NOESY NMR studies showed the ADen substituent to be included within the native β-CD and β-CD substituent cavities.Li Li, Xuhong Guo, Jie Wang, Peng Liu, Robert K. Prud’homme, Bruce L. May and Stephen F. Lincol