Method for the synthesis of uric acid derivatives.
A general procedure to obtain tetra-substituted uric acid by stepwise N-alkylation is described. 2,6-Dichloropurine (1) was condensed with 1-propanol by Mitsunobu reaction to give 9-propyl congener (2). Treatment of 2 with ammonia gave adenine derivative (4a), which was converted to the 8-oxoadenine (5b) in 3 steps. Methylation of 5b proceeded site-specifically to give 6-amino-2-chloro-7,8-dihydro-7-methyl-9-propylpurin-8-one (6) as a sole product. Compound 6 was successively treated with NaNO2 and iodomethane to give 2-chloro-1,6,7,8-tetrahydro-1,7-dimethyl-9-propylpurin-6,8-dione (9) accompanied by the O6-methyl product (8) in 75% and 6.9%, respectively. After nucleophilic substitution of 9 with NaOAc, the product (11) was reacted with iodomethane to give the uric acid (12) and the 2-methoxy product (13) in 46% and 15.5%, respectively. However, the reaction of 11 with the benzylating agents gave only O-benzyl products (14a,b).
Maruyama
T
T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan. maruyama@ph.bunri-u.ac.jp
Kozai
S
S
Sasaki
F
F
D000433:1-Propanol / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000478:Alkylation; D000641:Ammonia / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D013058:Mass Spectrometry; D008745:Methylation; D011687:Purines / Q000737:chemistry; D014527:Uric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D006847:Hydrocarbons, Iodinated; D011687:Purines; C002992:8-hydroxyadenine; D014527:Uric Acid; C031268:2,6-dichloropurine; C024829:8-hydroxyguanine; D006147:Guanine; D000641:Ammonia; D000433:1-Propanol; C014055:methyl iodide; D000225:Adenine