Microwave-assisted preparation of nucleoside-phosphoramidites

Abstract

Microwave-assisted phosphitylation of sterically hindered nucleosides is demonstrated to be an efficient method for the preparation of corresponding phosphoramidites (otherwise onerous under standard conditions) and is shown to be general in its applicability.

Chimeric XNA: An Unconventional Design for Orthogonal Informational Systems

“…Monomer synthesis : Ribulofuranoside ( r t and r a ) phosphoramidite monomers were synthesized as outlined in the literature, and the synthesis of both r c and r g phosphoramidite intermediates are outlined in the Supporting Information (Sections 2.1–2.2). Microwave‐assisted phosphitylation of all four ( r t , r a , r c and r g ) phosphoramidites was carried out as described in literature …”

“…Microwave-assisted phosphitylation of all four ( r t, r a, r c and r g)p hosphoramidites was carried out as described in literature. [39] Oligonucleotide synthesis:A ll modified oligonucleotides were synthesized in-house through automated solid-support DMT-phosphoramidite chemistry as described in the literature [40] using slightly modified reagents, coupling protocols and deprotection/purification strategies (see Supporting Section 4.0). Biophysical analysis:Oligonucleotide samples (single-and doublestranded) were analyzed by UV-monitored thermal denaturation experiments, monitored at l 254, 260 and 272 nm.…”

Microwave‐Assisted Phosphitylation of DNA and RNA Nucleosides and Their Analogs

“…2.19.3). The demonstration of reduced reaction times and adequate-to-high yields (Meher et al, 2014) illustrates the potential of microwave-assisted phosphitylation as an extremely facile and efficient method with which industry can produce large quantities of phosphoramidites with considerable time and potential cost savings. In addition to demystifying the common perception about the sensitivity of phosphoramidite chemistry to elevated temperatures, this protocol demonstrates that one can phosphitylate both DNA and RNA nucleoside monomers with the help of microwave irradiation using the most common phosphitylating reagent.…”

“…For synthesis of phosphoramidite building blocks in the sterically hindered ribulofuranosyl series of nucleoside analogs (Stoop et al, 2013), the development of an efficient and high-yielding phosphitylation procedure was crucial. The phosphitylation strategy had to be unique in nature, because extended reaction times under standard phosphitylating conditions, coupled with different protecting groups produced inadequate results (Meher et al, 2014). Since alternative phosphitylating reagents such as 2-cyanoethyl-N, N-diethylamino chlorophosphoramidite or 2cyanoethyl-N,N,N ,N -tetraethylamino phosphane were difficult to acquire and inherently more unstable, it was postulated that better results could be obtained through another strategy.…”

“…While attempting to chemically phosphitylate a series of novel nucleoside analogs based on a ribulofuranosyl sugar scaffold (1a-d; Meher and Krishnamurthy, 2011), it became clear that typical phosphitylating techniques would not efficiently produce the desired phosphoramidite products in decent yields or in a timely manner. To help expedite the phosphitylation process, microwave irradiation was employed (Meher et al, 2014). This approach was attempted to address the reported sensitivity of phosphitylating reagents and ribulosebased phosphoramidite products to elevated temperatures (Caruthers et al, 1987).…”