Synthesis of Organometallic Oligonucleotides through Oximation with Metalated Benzaldehydes

Abstract

A phthaloyl-protected aminooxymethyl-C-2′-deoxyriboside building block has been prepared and incorporated in the middle of an oligodeoxyribonucleotide. Removal of the phthaloyl protection followed by on-support oximation with either mercurated or palladated benzaldehydes yielded oligonucleotides bearing the respective benzaldoxime metallacycles.

Still Elusive – Pd(II)‐Mediated Base Pairing by an Acetophenone Oxime Palladacycle within 15N‐Labelled Double‐Helical Oligonucleotides

“…RP‐HPLC analysis of the product mixture revealed several new peaks (chromatograms presented in the Supporting Information). This phenomenon has been reported before [28–30,40,41] and attributed to relatively slow ligand exchange at Pd(II). The collected fractions were analyzed by ESI‐TOF‐MS and those showing addition of a single Pd(II) ion combined.…”

N-Methoxy-1,3-oxazinane nucleic acids (MOANAs) – a configurationally flexible backbone modification allows post-synthetic incorporation of base moieties

“…Of the commonly used conjugation reactions, oximation yields the smallest linkage and we have had some success using it for the incorporation of metallacyclic benzaldehydes into aminooxy-functionalized oligonucleotides. 30,31 However, even in that case the sugar and base moieties were separated by an additional oxymethylene linker. With a PNA backbone, "base filling" through peptide coupling and reductive amination has met with considerable success 32 but, to the best of our knowledge, the feasibility of a similar strategy with a sugar phosphate backbone remains to be demonstrated.…”

Organomercury Nucleic Acids: Past, Present and Future

“…In such cases, the organomercury moiety can first be synthesized separately using whatever conditions necessary and then introduced to the oligonucleotide by suitable conjugation chemistry. The feasibility of this strategy has been demonstrated recently by oximation of a support‐bound aminooxy‐functionalized oligonucleotide with 2‐mercury‐3‐hydroxybenzaldehyde [18] …”

“…The feasibility of this strategy has been demonstrated recently by oximation of a supportbound aminooxy-functionalized oligonucleotide with 2-mercury-3-hydroxybenzaldehyde. [18]…”