Normand Hebert

SYNTHESIS OF OXADIAZOLES ON SOLID SUPPORT

Abstract Aliphatic and aromatic nitriles linked to solid support were converted to amide oximes, and cyclized to oxadiazoles using N -protected amino acid anhydrides. The amino protecting group was removed and the products acylated or sulfonylated on resin to provide combinatorial libraries of oxadiazoles.

Synthesis of N-substituted hydroxyprolinol phosphoramidites for the preparation of combinatorial libraries

Abstract A series of N-substituted DMT-hydroxymethylpyrrolidinol phosphoramidites has been prepared from trans-4-hydroxyproline. These can be coupled in high yield and purity using automated synthesis techniques, allowing a wide range of functionalities to be introduced into phosphodiester oligomers.

Solid-phase synthesis of a library of functionalized aminodiol scaffolds

A combinatorial library motif has been developed based on orthogonally protected aminodiol scaffolds. Amine functionality was derivatized by commercially available electrophiles including carboxylic acids, sulfonyl chlorides, isocyanates, and aldehydes. A hydroxyl moiety was converted to a carbamate linkage, allowing a variety of amines to be incorporated. The scaffold was anchored to TentaGel at the second hydroxyl via a succinyl linker, which was hydrolyzed by mild aqueous basic conditions. The method was used to make a library of about 17,000 different members in mixtures of 5 per sample.

Synthesis of Fluorescent Cationic Lipids for Evaluation of Cellular Pathways and Delivery Mechanisms of Antisense Oligonucleotides

Abstract The synthesis of BODIPY conjugated cationic lipids was achieved in three steps from 3-bromopropane-1,2 diol as the starting material. These compounds were evaluated for their ability to enhance cellular uptake of the antisense oligonucleotides.