Synthesis and Anti-HIV Activity of Alkyl Steroidal 3′-Azido-3′-deoxythymidin-5′-yl Phosphotriesters as Prodrugs of AZT

Nucleotides. Part XLVII. Synthesis of 3′‐Deoxyadenylyl‐(2′–5′)‐3′‐deoxyadenylyl‐(2′–5′)‐3′‐O‐(2‐hydroxyethyl)adenosine and 3′‐Deoxyadenylyl‐(2′–5′)‐3′‐deoxyadenylyl‐(2′–5′)‐3′‐O‐{2‐[(cholest‐5‐en‐3β‐yloxy)carbonyloxy]ethyl}adenosine: A New Type of (2′–5′)Adenylate Trimer Conjugate

“…More recently, it was shomn [12] that the antiviral activity of the cordycepin trimer core 3'd(A2'p5'A2'p5'A) can be augmented up to 1000-fold by the introduction of lipophilic moieties such as cholesterol (cholest-5-en-3P -01). Cholesterol improves most likely cell penetration of the polyanionic oligonucleotides [13][14][15][16][17][18][19][20]. Contrary to the wide-spread practice using phosphordiester bonds for conjugate coupling [21], Wusner et al [ 121 attached the cholesterol moiety via ester linkages to the 2'and 5'-end of the cordycepin trimer core.…”