A CAUTIONARY NOTE ON THE USE OF THE ³¹P NMR SPECTROSCOPY IN STEREOCHEMICAL CORRELATION ANALYSIS

Abstract

Stereoselectivity in condensation of protected ribonucleoside 3'-H-phosphonates with hydroxylic components was investigated using 31P NMR spectroscopy. The correlation between absolute configuration at the phosphorus center and the chemical shifts of the produced H-phosphonate diesters and the corresponding phosphorothioates, was studied.

Discovery and characterization of stereodefined PMO-gapmers targeting tau

“…X-ray crystal structure of a TA dinucleotide was obtained to unambiguously determine the absolute stereochemistry of phosphorus atom and to deduce the absolute stereochemistry of activated A monomer given that the presumed mechanism of the coupling reaction would involve inversion of configuration at the phosphorus stereogenic center (37). The phosphorus stereochemistry of the rest of the dinucleotides and the activated monomers were then assigned based on the relative 31 P NMR chemical shift comparison with those of PMO A dinucleotide and monomer (38, 39).…”

“…The phosphorus stereochemistry of the rest of the dinucleotides and the activated monomers were then assigned based on the relative 31 P NMR chemical shift comparison with those of PMO A dinucleotide and monomer (38,39).…”

Chemistry and stereochemistry of internucleotide bond formation by the H-phosphonate method

“…Therefore, such correlation must be treated with care and as a provisional guide only. 42 In a typical condensation, a triethylammonium salt of the nucleoside 3 0 -H-phosphonate of type 1 and a nucleoside (both appropriately protected) are dissolved in pyridine and ca. 3 equiv.…”

“…This paper summarises the studies into stereoselective condensations of ribonucleoside 3 0 -H-phosphonates with alcohols and nucleosides that have been conducted in our laboratory in recent years. 41,42,45,46,52,53,60 The collected data indicate that these reactions owe their stereoselectivity to a dynamic kinetic asymmetric transformation (DYKAT) type of asymmetric induction, which is based on diverse reactivity of D P and L P diastereomers of the reactive intermediate, H-phosphonic-pivalic mixed anhydride, towards alcohols.…”

Novel bile acid derived H‐phosphonate conjugates: Synthesis and spectroscopic characterization

“…The structures of these newly synthesized Hphosphonate and phosphoramidate bile acid conjugates have been well confirmed by IR, 31 P NMR, 1 H NMR, and HRMS. Because the phosphorus in every H-phosphonate group is chiral and can readily change configuration between R and S, one bile acid H-phosphonates conjugate was in fact the mixture of several diastereoisomers [17,18]. Considering the fact that the corresponding carbons on the steroid nucleus (3-C, 7-C, and 12-C) are also chiral atoms, the splitting caused by the presence of diastereoisomers can be observed in both 31 P and 1 H NMR spectra.…”