Sustainable Protocol for the Synthesis of 2′,3′-Dideoxynucleoside and 2′,3′-Didehydro-2′,3′-dideoxynucleoside Derivatives |
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Authors: | Virginia Martí n-Nieves,Yogesh S. Sanghvi,Susana Ferná ndez,Miguel Ferrero |
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Affiliation: | 1.Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33006 Oviedo, Spain;2.Rasayan Inc., Encinitas, CA 92024, USA; |
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Abstract: | An improved protocol for the transformation of ribonucleosides into 2′,3′-dideoxynucleoside and 2′,3′-didehydro-2′,3′-dideoxynucleoside derivatives, including the anti-HIV drugs stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), was established. The process involves radical deoxygenation of xanthate using environmentally friendly and low-cost reagents. Bromoethane or 3-bromopropanenitrile was the alkylating agent of choice to prepare the ribonucleoside 2′,3′-bisxanthates. In the subsequent radical deoxygenation reaction, tris(trimethylsilyl)silane and 1,1′-azobis(cyclohexanecarbonitrile) were used to replace hazardous Bu3SnH and AIBN, respectively. In addition, TBAF was substituted for camphorsulfonic acid in the deprotection step of the 5′-O-silyl ether group, and an enzyme (adenosine deaminase) was used to transform 2′,3′-dideoxyadenosine into 2′,3′-dideoxyinosine (ddI) in excellent yield. |
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Keywords: | 2′ ,3′ -dideoxynucleosides, 2′ ,3′ -didehydro-2′ ,3′ -dideoxynucleosides, synthesis, zalcitabine (ddC), didanosine (ddI), stavudine (d4T) |
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