Sustainable Protocol for the Synthesis of 2′,3′-Dideoxynucleoside and 2′,3′-Didehydro-2′,3′-dideoxynucleoside Derivatives

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.

Automated summary

An improved protocol for the transformation of ribonucleosides into anti-HIV drugs and other nucleoside derivatives has been established. The protocol uses environmentally friendly and low-cost reagents for deoxygenation reactions and can substitute hazardous reagents commonly used.