The synthesis of a series of purine analogues of the acyclonucleoside compound A* (A-Star, 1) is described. Compounds in this series have been shown to have pronounced activity against herpesviruses. These compounds have been designated "the glycerosides". The glyceropurines are described in this report. Nucleotides have been constructed containing glyceroadenine (A*, compound 1). These nucleotides are resistant to degradation by phosphodiesterases. The compound A* is both a poor substrate and a poor inhibitor of adenosine deaminase.

Can. J . Chem. 60, 3005 (1982). The chemical synthesis of 9-[[2-hydroxy-l-(hydroxymethyl)ethoxy]methyl]guanine is described. This compound, known a s BIOLF-62, is active against herpesviruses. This compound is a member of a novel class of nucleoside analogues which lacka rigid carbohydrate ring, but which possess all of the functional groups of naturally occurring deoxynucleosides. I The search for biologically active molecules has ' focused a great deal of attention on modified nucleosides (1-3). For several years we have been i developing a nucleoside analogue structure intended to interfere with viral and bacterial systems. The I structure was designed to lack the rigid conformal tional feature (syn-anti) of natural nucleosides but i at the same time retain the essential chemical features of natural nucleosides (e.g., purine or I pyrimidine ring, 03', 0 4 ' , and Os'oxygen functionalities). In a preliminary report (4) we described the synthesis of the adenine analogue 9[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]adenine. This compound was neither a substrate nor an inhibitor for adenosine deaminase, a key enzyme in animal systems that inactivates in vivo most adenine derivatives that show promising biological activity in vitro. In this report we wish to describe the synthesis of another member of this series, the potent antiviral compound 9[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (5) which is known as BIOLF-62. Results and discussionThe first route fully explored for the synthesis of BIOLF-62 involved the condensation of 6-chloro-I

Several routes for the synthesis of triquinacene (1) and 2,3-dihydrotriquinacen-2-one (3) are described using Thiele's acid as starting material.

; i/c S l~c i~h i~o o X~~, Shci.hi.ooXc (Qirc;.). C'cillcitl(i J I K ZRI Received Fehruar! 27. 1979 T h i~ piipci. is cladic,atrd f r j Prof. Knrel W i e~i~r i . orl the oc~ccision of his 60th hirtlzd~?.PIERRE DESLONGCHAVPS, UKKEN OUSEPH CHERIYAN, and ROLAND J. TAILLEFER. Can. J. Chem. 57. 3262 (1979).The synthesis and the hydrolytic behavior of the cyclic imidate salts 7,8, and 9 is reported. Under acidic conditions, the salt 7 gives the ester ammonium salt 21 and the salt 9 gives a 1 : 1 mixture of the ester ammonium salt 22 and the amide alcohol 23 as the rotamer 23B only. Under basic conditions, the salt 7 (or 8) gives a 2:8 (or 1 :9) mixture of the amide alcohol rotamers 25A and 25B (or 27A and 27B) under kinetically controlled conditions. The salt 9 gives, as the kinetic product, the amide alcohol rotamer 23B only. These results can be rationalized on the basis of the stereoelectronic theory for the cleavage of tetrahedral intermediates and by taking into account that the nitrogen in tetrahedral intermediates must be either protonated under acidic conditions, or hydrogen bonded with the solvent under basic conditions, in order to observe the cleavage of a C-N bond.

9-[[2-Hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (BIOLF-62) is highly synergistic with either phosphonoformate or phosphonoacetate when used in combination against herpes simplex virus types 1 and 2 in vitro. Acycloguanosine did not show significant synergism with these two compounds. Bromovinyldeoxyuridine and phosphonoformate were highly synergistic against herpes simplex virus type 2, but not against type 1.