Design, synthesis,?and biological evaluation of C1-phosphonamidate analogues of 2-deoxy-d-ribose-1-phosphate

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• 作者：Maurizio Quintiliani ; Jan Balzarini ; Christopher McGuigan
• 关键词：Deoxyribose ; Phosphorylation ; Phosphonates ; Phosphonamidates
• 刊名：Tetrahedron
• 出版年：2013
• 出版时间：28 October, 2013
• 年：2013
• 卷：69
• 期：43
• 页码：9111-9119
• 全文大小：464 K

文摘

A novel series of phenoxy C1-phosphonamidate derivatives of 2-deoxy-d-ribose have been synthesised as stable analogues of 2-deoxy-¦Á-d-ribose-1-phosphate. A number of synthetic routes were explored for the preparation of these targets. The successful approach involved the synthesis of a protected C1-phosphonate ester dFont"">17 via Michaelis-Arbuzov reaction, which was then hydrolysed and coupled with different amino acid esters using aldrithiol. Subsequent hydrogenolysis afforded the targets dFont"">2a-dFont"">g, which were isolated as a mixture of diastereoisomers. The compounds were assayed for inhibition of thymidine phosphorylase (TP) and uridine phosphorylase (UP) and for antiviral and cytostatic activity.