3 research outputs found
Asymmetric Synthesis of Cyclohexene Nucleoside Analogues
The asymmetric synthesis of novel cyclohexene nucleoside
analogues 12 and 15 is described. An enantiospecific DielsAlder
reaction between (E,E)-diene 2 and (+)-5-(D-mentyloxy)-2(5H)-
furanone 3 provided the cycloadduct isomer 4. Three additional steps
yielded amine 8 allowing the constructions of the thymine and adenine
moieties to afford intermediates 11 and 14, respectively. Amination or
cyclization and removal of the protecting groups occurred in one step
in the presence of ammonia, giving the target six-membered ring
nucleosides
Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone
Synthesis of a novel archaeal tetraether-type lipid containing a diorthoester group as a helper lipid for gene delivery
International audienceAs an alternative to recombinant virus, synthetic carriers are widely developed for providing efficient and safe DNA delivery. To reach the nucleus where nucleic acid (NA) constructs are transcripted, chemical complexes have to overcome serious cellular traps such as endosomal escape and intracellular trafficking. Here, the design and the multi-step synthesis of a stabilizing tetraether lipid analogue of archaeal counterparts containing a diorthoester moiety in the middle of the bridging chain were described. The key step involved a double coupling reaction between two diether alcohols and a diketene acetal. Under aqueous acidic conditions, the diorthoester function of the tetraether lipid can be hydrolysed to yield two monopolar diether lipids. Applied to gene delivery in association with a cationic lipid, this new helper bipolar tetraether lipid led to lipid-DNA complexes with sizes and potential zeta values depending on the charge ratios (+/-). In addition, preliminary in vitro transfection assays supported the interest of these novel bipolar lipid-based lipoplex formulations compared to standard Lipofectamine-based formulations. © 2016 Elsevier Ltd. All rights reserved