Purine Nucleoside Analogues. 10. A New Synthetic Route to 8-Substituted-7(9)-Alkoxyalkylguanines

Abstract

The N-alkoxyalkylation of 8-bromo-N'-acetylguanine I with α-halogen and a-acetoxy ethers has been investigated. Treatment of I with 2-haloethyl chloromethyl ethers in the presence of potassium carbonate afforded 8-bromo-7-and 8-bromo-9-alkoxyalkyl-N 2 -acetylguanines in high overall yields. Without added base the replacement of the bromine atom for chlorine at the 8 position of the heterocycle occurred providing 8-chloro-7-and 8-chloro-9-alkoxyalkylated products. The acid catalyzed reaction of I with 2-acetoxyethyl acetoxymethyl ether afforded 8-bromo-7-and 8-bromo-9-(2-acetoxyethoxymethyl)-N 2 -acetylguanines.

The Determinative Influence of the O6-(Diphenylcarbamoyl) Group on the Exocyclic Nitrogen Benzylation in 2-Amino-6-oxopurine Derivatives

“…4 To determine the benzylation site in product 4f, it was deprotected to the corresponding 8-bromo-9-(3bromobenzyl)-2-[(3-bromobenzyl)amino]-1,9-dihydro-6H-purin-6-one (13a) whose NCH 2 group proton singlet at d = 5.37 corresponded to that in the similar N 9 -substituted purines. 10 The structure of product 6 was established as 9-(2-oxo-2-phenylethyl)purine by assuming that the reaction of purine 1 with bromide 2j follows the same direction as in the case of other arylalkylating agents used. The N 2 -arylalkylated derivatives of 2-(acetylamino)-6-(diphenylcarbamoyloxy)purine were also characterized by their 13 C NMR spectra.…”