Direct Assignment of the Absolute Configuration of a Distinct Class of Deoxyribonucleoside Cyclic N-Acylphosphoramidites at Phosphorus by M-GOESY Nuclear Magnetic Resonance Spectroscopy

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• 作者：Andrzej Wilk ; Andrzej Grajkowski ; Thomas E. Bull ; Ann M. Dixon ; Daró ; n I. Freedberg ; and Serge L. Beaucage
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：February 20, 2002
• 年：2002
• 卷：124
• 期：7
• 页码：1180 - 1181
• 全文大小：40K
• 年卷期：v.124,no.7(February 20, 2002)
• ISSN：1520-5126

文摘

The determination of the absolute configuration of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus toward the synthesis of P-stereodifined phosphorothioated oligodeoxyribonucleotides is easily accomplished with computer-assisted molecular modeling and M-GOESY NMR spectroscopy. Specifically, computer-modeling diasteromeric phosphoramidite 3 has identifed a proximal (2.55 Å) through-space interaction between benzylic H-5 and sugar H-2' ', which can predictably be detected by M-GOESY NMR in S_P-3 but not in R_P-3 because of being too distant (5.85 Å). Consistent with computer-assisted modeling predictions, M-GOESY NMR spectra of S_P-3 and R_P-3 revealed NOE signals generated from nuclei near the selectively excited H-2' ' that are common to both S_P-3 and R_P-3, namely those of H-2', H-4', H-3', and H-1'. In addition, a diagnostic NOE signal at 5.5 ppm (benzylic H-5) is, as predicted, only detected in S_P-3 and thus provides an unequivocal assessment of the configuration of the diastereomer at phosphorus. M-GOESY NMR data also confirm that the condensation of deoxyribonucleoside cyclic N-acylphosphoramidites with base-activated nucleosidic or nucleotidic 5'-hydroxyls proceeds via a single nucleophilic event.