Adenosine dideoxynucleosides

Singhal D, Ho NF and Anderson BD (1998) Absorption and Intestinal Metabolism of Purine Dideoxynucleosides and an Adenosine Deaminase-Activated Prodrug of 2/,3/-Dideoxyinosine in the Mesenteric Vein Cannulated Rat Ileum. J Pharm Sci 87 pp 569-577. 

Another route for the synthesis of azidonucleosides involved the transformation of preformed 3 -azido-2, 3 -dideoxynucleosides. These transformations usually follow standard procedures in nucleoside chemistry. 3 -Azido-2, 3 -dideoxy-inosine 7d has been prepared by deamination of the adenosine analogue 7a with adenosine deaminase [54]. A variety of 3 -azido-2, 3 -dideoxycytidine derivatives, such as 7b [36-38, 50], 7g [38], 7h [38], and 7i [38] have been prepared from the corresponding 3 -azido-2, 3 -dideoxyuridine and thymidine derivatives following known procedures for the amination at position 4. 3 -Azido-2, 3 -dideoxyuridine 7f has also been used as starting material for the synthesis of a variety of 3 -azido-2, 3 -dideoxy-5-substituted uridines, such as 7j-7m and 7p-7t [38, 51, 53]. 

The precursor for the synthesis of the anti-HIV inactive compound, 2-iododideoxy-adenosine, 7 (Scheme 4), was the 2-amino-6-chloropurine 2 ,3 -dideoxynucleoside, 5 Compound 5 and its 5 -derivatives 6 (e.g., 5 -acylatcd) exhibit in vitro anti-HIV activity with ECjn values in the range of 5-10 pM. Compound 5 is a substrate for the enzyme, ADA, and the mechanism of its antiviral activity appears to be associated with its cellular conversion by ADA to ddG (Fig. 1). Several other prodrugs of ddG have also been synthesized by us. 

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