Tlze by&h&..6 04 acy&Xc ana.&gues 06 2'-dw adeno~inine and 2'-dwxy.t&tidine which La& only tithe 2'-C/i2 06 the AUgah .i.~ deaai.bed. "il Te~ynthe& o,jdinucewa%.d66 @wmMese ana&gues & G.&O deai.kd.
Adenosine analogues have high potential as chemotherapeutic agents (1) but their practical value is often greatly reduced by their ready deamination in vivo by deaminases (2,3).
--Consequently, numerous investigations have been carried out to determine the relationship between structure and activity for both substrates and inhibitors of adenosine deaminase (4-10). Many of these studies have involved ring-opened analogues of adenosine (4,8,9,10).
Us Clercq has recently reported on the antiviral activity of a number of analogues of nucleosides and he found that (S)-9-(2,3dihydroxypropyl)adenine possesses selective antiviral activity (9). The 9-(Z-hydroxyethoxy) derivatives of adenine (10) and guanine (9,111 have proven to be very interesting compounds.
In addition to the interest in adenosine deaminase activity, ring-opened analogues of adenosine have been phosphorylated to provide novel nucleotide analogues (12-14). Smrt and his colleagues have looked at compounds J_ and 2 as flexible analogues (12) of natural enzyme substrates and in modified terminor and initiator codons (13). In addition Pandit reported the synthesis of several 4-hydroxy-3-(hydroxymethyljbutyl derivatives (2 of purines and pyrimidines with the reported intention of preparing nucleotide analogues from them (15). H T-3 d Hdd "V Hd 1 bH bH 2 (B = Ad,Cy,!th) We wish to describe the synthesis of the bis-(hydroxymethyl)methoxynmthyl derivatives of adenine (A*, 4, and thymine (T*, 21 and several dinucleoside monophosphates derived from them.
These compounds contain all of the functional characteristics (5'-hydroxyl,3'-hydroxyl,l'oxygen) of the natural nucleosides but they lack the rigid ring structure.