Synthesis of a novel cyclopropyl phosphonate nucleotide as a phosphate mimic.

The inherent in vivo instability of oligonucleotides presents one of many challenges in the development of RNAi-based therapeutics. Chemical modification to the 5'-terminus serves as an existing paradigm which can make phosphorylated antisense strands less prone to degradation by endogenous enzymes. It has been recently shown that installation of 5'-cyclopropyl phosphonate on the terminus of an oligonucleotide results in greater knockdown of a targeted protein when compared to its unmodified phosphate derivative.

Suzuki-Miyaura Coupling Reactions of Conjunctive Reagents: 2-Borylated Allylic Sulfones.

In support of various efforts in our group, we developed methods for the convenient Suzuki-Miyaura coupling of borylated allylic sulfones with various electrophiles in both inter- and the less common intramolecular modes. The procedure facilitates the preparation of a wide variety of sulfones in a straightforward fashion, including six- through eight-membered rings.

New synthesis of α'-hydroxydienones.

Herein, attempted oxidation of selected allenols with PCC affording α'-hydroxydienones rather than simple oxidation products is described. The formation of the products observed is rationalized via a series of sigmatropic shifts, followed by hydrolysis.

Generation and alkylation of 2-boryl allylic sulfone anions.

The deprotonation and electrophilic trapping of an allylic sulfone substituted at the 2 position by a pinacol boronate results in the formation of the corresponding alkylation products. The ability of the boronate ester to tolerate the sulfonyl carbanion suggests a broader application of the methodology to prepare a wide range of functionalized boronates.