An Investigation of the Reactions between Azido Alcohols and Phosphoramidites

Abstract

The reactions of several β-, γ-, and δ-azido alcohols with dibenzyl and dimethyl N,N-diisopropylphosphoramidites were examined. Detailed analysis of the intermediates and products formed from the reactions under different conditions provided useful information to gain insights into their mechanisms involving intramolecular Staudinger reaction, as well as the structure-reactivity relationships of both substrates. The reactions of γ- and δ-azido alcohols with dibenzyl N,N-diisopropylphosphoramidite could produce 6- and 7-membered cyclic phosphoramidates, thereby providing a new synthetic method for these biologically important molecules.

Regiodivergent and stereoselective hydroxyazidation of alkenes by biocatalytic cascades

“…Herein, facile synthesis of chiral 1,2-amino alcohols ( R )- 7a (41%, >99% ee ) and ( S ) -8a (58%, >99% ee ) was achieved via a simple reduction reaction of ( R )- 3a and ( S )- 4a , respectively ( Figure 7 ). In addition, many other useful chiral heterocyclic scaffolds could be obtained according to previous studies of transformations of 1,2-azidoalcohols ( Ariza et al., 2001 ; Chakraborty et al., 2005 ; Ittah et al., 1978 ; Li et al., 2009 ; Sahasrabudhe et al., 2003 ; Sun et al., 2015 ; Wu et al., 2019 ; Yang and Lu, 2017 ). These representative transformations clearly demonstrate the versatilities of these enantiopure 1,2-azidoalcohols.…”

Azido Functionalized Nucleosides Linked to Controlled Pore Glass as Suitable Starting Materials for Oligonucleotide Synthesis by the Phosphoramidite Approach

“…Toluene was dried over CaH 2 and distilled onto 3 Å molecular sieve. 1 H, 13 C and 19 F NMR spectra were recorded on a Bruker Avance III 400 or 500 MHz instrument or a Bruker Avance Neo 600 MHz spectrometer. The chemical shifts were referenced to the residual…”

“…Expected Ratio of A* to dC [a] Detected Ratio of A* to dC [a] Normalized Ratio of A* to dC [a] ODN proton signal of the deuterated solvents relative to TMS: DMSO-d 6 (2.50 ppm) for 1 H NMR spectra; DMSO-d 6 (39.52 ppm) for 13 C NMR spectra. 19 F NMR spectra were indirectly referenced to CCl 3 F. [31] 1 H and 13 C assignments were based on COSY, HSQC and HMBC experiments. MS measurements were performed on a Bruker microflex MALDI-Tof MS with 3-hydroxypyridine-2-carboxylic acid (HPA) being used as a matrix.…”

“…The mixture was stirred for 30 min at room temperature after which the solvents were removed. The oily residue was co-evaporated three times with 10 ml toluene and purified by column chromatography (2 s, J = 1.3 Hz, 6H, OÀ CH 3 ), 3.25 (m, 2H, H2-C(5')), 2.96 (sept, J = 6.9 Hz, 1H, À CHÀ (CH 3 ) 2 ), 1.13 (J 1 = 0.9 Hz, J 2 = 6.9 Hz, 6H, À CHÀ (CH 3 ) 2 ); 13…”

“…[12] Furthermore, the reactivity of azides towards phosphoramidites has been used intentionally to produce cyclic phosphoramidates and phosphorazides. [13] Owing to this reactivity, azido modifications are often inserted into oligonucleotides enzymatically, [14,15] or chemically after solid phase ON synthesis has been concluded. [16][17][18] H-phosphonate or phosphotriester chemistry was also used instead of the phosphoramidite approach for the synthesis of azido-modified oligonucleotides, [19][20][21] or synthesis of 3'-terminal azido modified ODNs was conducted in reverse orientation from 5' to 3'-end.…”