2'-Modified Thymidines with Bioorthogonal Cyclopropene or Sydnone as Building Blocks for Copper-Free Postsynthetic Functionalization of Chemically Synthesized Oligonucleotides.

The development of facile methods for conjugating relevant probes, ligands, or delivery agents onto oligonucleotides (ONs) is highly desirable both for fundamental studies in chemical biology and for improving the pharmacology of ONs in medicinal chemistry. Numerous efforts have been focused on the introduction of bioorthogonal groups onto phosphoramidite building blocks, allowing the controlled chemical synthesis of reactive ONs for postsynthetic modifications. Among these building blocks, alkyne, cyclooctynes, trans-cyclooctene, and norbornene have been proved to be compatible with automated solid-phase chemistry. Herein, we present the development of novel 2'-functionalized nucleoside phosphoramidite monomers comprising bioorthogonal methylcyclopropene or sydnone moieties and their introduction for the first time to ON solid-phase synthesis. Traceless ON postsynthetic modifications with reactive complementary probes were successfully achieved through either inverse electron-demand Diels-Alder (iEDDA) reactions or strain-promoted sydnone-alkyne cycloaddition (SPSAC). These results expand the set of bioorthogonal phosphoramidite building blocks to generate ONs for postsynthetic labeling.

A method for the net contra-thermodynamic isomerization of cyclic trisubstituted alkenes.

A simple sequence for the net contra-thermodynamic isomerization of cyclic trisubstituted alkenes is reported consisting of a radical addition of p-chlorothiophenol, followed by oxidation to the sulfoxide and thermal syn-elimination to give the least substituted isomeric cycloalkene.

A convergent approach to polycyclic aromatic hydrocarbons.

A new concise route to Polycyclic Aromatic Hydrocarbons (PAHs) through radical addition and cyclisation of xanthates is described.