Studies on the Alkylation of Guanine. 2. The Synthesis of Acyclic Guanosine Analogs via the Precursor 7-Methyl-10-oxo-9,10-dihydropyrimido[1,2-a]purine.

New Approach to the Synthesis of N7‐Arylguanines and N7‐Aryladenines

“…In contrast to the guanine derivatives, o-phenanthroline as the base/ligand gave a better yield and higher N 7 selectivity than TMEDA (Table 5). We also observed the presence of 15 % N 9 -phenyladenine (18) in the reaction mixture when methanol was used as the solvent. The formation of N 3 -arylated adenine was not detected.…”

“…Herein we describe the application of this methodology to the preparation of N 7 -arylguanine and -adenine derivatives, respectively. To overcome the low solubility of guanine, its derivatives, 7-methylpyrimido[1,2-a]purin-10(3H)-one (1) [18] and N 2 -(dimethylamino)methyleneguanine (2), [19] which can easily be converted to unprotected guanine derivatives, were used as the starting compounds ( Figure 1). …”

Syntheses of 7‐(2‐Hydroxy‐1‐phenylethyl)‐ and 7‐(2‐Hydroxy‐2‐phenylethyl)guanine, DNA Adducts Derived from Styrene 7,8‐Oxide

“…A similar observation was reported earlier for alkylation of 5 with 4-bromobutyl acetate in the presence of different bases such as sodium hydride, potassium carbonate, triethylamine, thallium() ethoxide and lithium diisopropylamide. [12] The three alkylating agents used (8a, 8b and 9b) showed a similar reactivity but compound 8a gave somewhat lower yields with benzylic bromide (Scheme 4, Table 2). The products of alkylation were separated and pure N-1 isomers 19a or 19b were deprotected by hydrolytic cleavage followed by palladium-catalysed deallylation [18] to yield the N-7 guanine derivatives 2a and 2b, respectively.…”

“…Pyrimidopurine 5 was introduced by Kjellberg et al [12] as a more stable, if not more reactive, guanine precursor for alkylation at N-7 and N-9 positions than both imidazopurines 3 and 4. It can be prepared by condensation of guanine with methylmalondialdehyde as described by Moschel and Leonard.…”

“…Several precursors to guanine with enhanced selectivity of alkylation have been reported in the literature, such as 6,7-diacetoxy-5-acetyl-5,6,7,9-tetrahydro-9-oxo-3H-imidazo[1,2-a]purine (3), [11] 5-acetyl-6,7-bis(2-methylpropanoyloxy)-5,6,7,9-tetrahydro-9-oxo-3H-imidazo[1,2-a]purine (4), [11] 7-methyl-10-oxo-9,10-dihydropyrimido[1,2-a]purine (5) [12] and 2-amino-6-chloropurine (6). [6] In our preliminary report we described a synthetic route to compounds 2a and 2b based on the alkylation of 2-amino-6-chloropurine (6) with allyl-protected bromohydrins as synthetic equivalents to 1.…”