New developments in the asymmetric synthesis of heterocyclic natural products

International audienceVarious chiral α,β-unsaturated γ-lactams 1 were prepared in high yield and in a single step from corresponding primary amines. The different reactivities of lactams 1 could be exploited to prepare diversely substituted pyrrolidones, pyrrolidines, γ-aminoacids and alkaloids. Their application to the synthesis of enantiomerically pure (-)-cephalotaxine are described

Synthesis and transfection properties of a series of lipidic neamine derivatives

International audienceWith the view to develop novel bioinspired nonviral vectors for gene delivery, we synthesized a series of cationiclipids with a neamine headgroup, which incorporates rings I and II of the natural antibiotic aminoglycoside neomycin B. Indeed, we reasoned that neamine might constitute a straightforward and versatile building block for synthesizing a variety of lipophilic aminoglycosides and modulating their characteristics such as size, topology, lipophilicity, number of charges, and charge density. Neamine derivatives bearing long dialkyl chains, one or two neamine headgroups, and four to ten protonatable amine functions were prepared through the selective alkylation of the 4′- or 5-hydroxyl function in ring I and ring II of neamine, respectively. The transfection activity of the twelve derivatives synthesized was investigated in Vitro in gene transfection experiments using several mammalian cell lines. The results allowed us to unveil interesting structure-activity relationships and to identify a formulation incorporating a small neamine derivative as a highly efficient gene delivery system

Synthesis of β‐Cyclodextrin Containing Copolymer via “Click” Chemistry and Its Self‐Assembly in the Presence of Guest Compounds

We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one β‐cyclodextrin (β‐CD) containing block by a “click” reaction between azido‐substituted β‐CD and propargyl flanking copolymer. 1 H NMR study suggested a highly efficient conjugation of β‐CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. The synthesis of β‐cyclodextrin containing block copolymer via a “click” reaction is reported. The self‐assembly of this newly synthesized copolymer in the presence of guest compounds can lead to the formation of core–shell structured nanoparticles. These assemblies can be employed as novel delivery vehicles for therapeutics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/1/marc_201100814_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/2/664_ftp.pd