Novel method for the synthesis of dinucleoside-(N3′→P5′)-phosphoramidothioates

• Published in: Tetrahedron letters Vol. 58; no. 23; pp. 2276 - 2279
• Main Authors: Kulik, Katarzyna, Kaczmarek, Renata, Baraniak, Janina, Ślepokura, Katarzyna, Gryaznov, Sergei
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 07.06.2017; Elsevier
• Subjects: Absolute configuration; Chemistry; Chemistry, Organic; Dinucleoside-(N3′ → P5′)-phosphoramidothioates; Nucleoside H-thiophosphonates; P-chirality; Physical Sciences; Science & Technology; X-ray diffraction analysis; Nucleoside H-thiophosphonates; P-chirality; Dinucleoside-(N3′→P5′)-phosphoramidothioates; X-ray diffraction analysis; Absolute configuration; POTENTIAL THERAPEUTIC AGENTS; TELOMERASE INHIBITORS; OLIGODEOXYRIBONUCLEOTIDE; Dinucleoside-(N3 ' -> P5 ')-phosphoramidothioates; ANTISENSE OLIGONUCLEOTIDES; CANCER
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2017.04.094

[Display omitted] •A new synthesis of dinucleoside-(N3′→P5′)-phosphoramidothioates has been developed.•Nucleoside H-thiophosphonates and 3′-amino-nucleosides were used as synthons.•A mixture of P-diastereomers of the dinucleosides was separated by chromatography.•The absolute configuration at the P-atom in the GNPSGNHTr has been assigned. A new approach for the synthesis of dinucleoside-(N3′→P5′)-phosphoramidothioates based on the Atherton–Todd reaction has been developed using nucleoside H-thiophosphonates and 3′-amino-2′,3′-dideoxynucleosides with an unprotected 5′-hydroxyl group. A mixture of P-diastereomers of dinucleosides was separated by column chromatography into fast migrating and slow migrating isomers. Based on single crystal X-ray diffraction analysis, the absolute configuration at the phosphorus atom in the slow eluting diastereomer of the dinucleoside-(N3′→P5′)-phosphoramidothioate GNPSGNHTr was assigned as Rp.