Abstract
Search for a new α-methylene-γ-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, 5′-Methyl-5′-[(6-substituted-9H-purin-9-yl)methyl]-2′-oxo-3′ methylenetetrahydrofurans (H, Cl, I, CH3, NH2, SH, >C=O) (6a-g). These include 5′-Methyl-5′-[(9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6a), 5′-Methyl-5′-[(6-chloro-9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6b), 5′-Methyl-5′-[(6-iodo-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6c), 5′-Methyl-5′-[(6-methyl-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6d), 5′-Methyl-5′-[(9H-adenin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6e), 5′-Methyl-5′-[(6-mercapto-9H-purin-9-yl) methyl]-2′-oxo-3′-methylenetetrahydrofurans (6f) and 5′-Methyl-5′-[(9H-hypoxanthin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans (6g) which were made by the Reformatsky-type reaction of ethyl α-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone, (5b), 1-(6-iodo-9H-purin-9-yl)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (5e), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of K2CO3 (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic α-methylene-γ-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity (IC50 ranged from 1.4 to 4.3 μg/ml) with the compound 5′-methyl-5′-[(9H-hypoxanthin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofuran (6g) showing the least antitumor activity.
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Kim, J.C., Kim, SH., Kim, JA. et al. Potential antitumor α-methylene-γ-butyrolactone-bearing nucleic acid base. 3. Synthesis of 5′-Methyl-5′-[(6-substituted-9H-purin-9-yl)methyl]-2′-oxo-3′-methylenetetrahydrofurans. Arch. Pharm. Res. 21, 458–464 (1998). https://doi.org/10.1007/BF02974643
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DOI: https://doi.org/10.1007/BF02974643