New TFA-Free Cleavage and Final Deprotection in Fmoc Solid-Phase Peptide Synthesis: Dilute HCl in Fluoro Alcohol

A novel method for cleaving from resin and removing acid-labile protecting groups for the Fmoc solid-phase peptide synthesis is described. 0.1 N HCl in hexafluoroisopropanol or trifluoroethanol cleanly and rapidly removes the <i>tert</i>-butyl ester and ether, Boc, trityl, and Pbf groups and cleaves the common resin linkers: Wang, HMPA, Rink amide, and PAL. Addition of just 5–10% of a hydrogen-bonding solvent considerably retards or even fully inhibits the reaction. However, a non-hydrogen-bonding solvent is tolerated

Efficient Functionalization of Oligonucleotides by New Achiral Nonnucleosidic Monomers

A novel synthetic strategy has been designed for preparation of achiral nonnucleosidic phosphoramidite monomers for automated solid-phase oligonucleotide synthesis. It is based on <i>O</i>-DMTr-protected 4-(2-hydroxyethyl)-morpholine-2,3-dione as the key compound and a family of building blocks obtained by its ring-opening by primary aliphatic amines. A series of nonnucleosidic phosphoramidites containing various side-chain functionalities was synthesized, and corresponding oligodeoxyribonucleotides incorporating modified units in single or multiple positions along the chain were prepared