A versatile new synthetic route to 2,4-diamino-6-substituted pteridines is described. Reaction of an -ketoaldoxime with aminomalononitrile gives 2-amino-3-cyano-5-substituted pyrazine 1 -oxides which yield 2,4diamino-6-substituted pteridine 8-oxides upon cyclization with guanidine. 2,4-Diaminopteridines are then obtained by deoxygenation of the corresponding 8-oxides, or alternately by prior deoxygenation of the above pyrazine 1-oxides, followed by cyclization with guanidine. The conversion of 2-amino-3-cyano-5-methylpyrazine 1-oxide to the corresponding 1,4-dioxide, and a number of chemical transformations of this latter intermediate, are also described.

Several new substituted trityl protecting groups have been prepared and investigated. They are di(p-benzyloxyphenyl )phenylmethanol (2a), (p-hydroxyphenyl )diphenylmethanol (2b), (p-acetoxyphenyl )diphenylmethanol (2c), (m-hydroxyphenyl)diphenylmethanol ( 2d), (m-acetoxyphenyl)diphenylmethanol (2e), and (p-bromophenacyloxyphenyl)diphenylmethanol (2f). Comparison of the rates of detritylation of the corresponding 5'trityladenosine derivatives by acetic acid showed that the (p-hydroxyphenyl )diphenylmethyl group could be removed under mild conditions in a reasonable length of time. However, this group cannot be used directly in oligonucleotide synthesis, without protection of the phenolic function. Consequently the trityl chloride (pbromophenacyloxyphenyl)diphenylmethyl chloride (BPTrCl) (3f) was used as the phenacyl ester is cleaved by mild reduction with zinc and acetic acid to give the p-hydroxytrityl group. Two dinucleoside monophosphates TpT (5a) and d-UpT (5b) have been synthesized using the BPTr group for protection of the 5'-hydroxyl position.The removal of the protecting group was studied both in the presence and absence of other acyl protecting groups.Application to the ribose series was investigated by the preparation of the dinucleoside monophosphate 5'-BPTr-UpU ( 12) and the trinucleoside diphosphate 5'-BPTr-UpUpU (15). Removal of the BPTr group from these compounds was achieved with 20% acetic acid and zinc dust. However, it was found that the presence of other acyl protecting groups complicated the detritylation when using zinc and acetic acid, so that for further synthetic work detritylation was achieved with formic acid. (1960),(2) The system of abbreviations used in this paper is that of H. G. Khorana's group; compare, for example, H.