Purine Nucleosides. I. The Synthesis of Certain 6-Substituted-9-(tetrahydro-2-pyranyl)-purines as Models of Purine Deoxynucleosides¹

Abstract

2,3-Dihydro-4H-pyran and various 2-substituted 2,3-dihydro-4H-pyrans have been shown to react with certain 6-substituted purines in the presence of a catalytic amount of acid to give the corresponding 6-substituted-9-(tetrahydro-2-pyrany1)-purines. This reaction provides a new synthetic route to the preparation of valuable models of certain purine deoxynucleosides which possess significant antitumor activity. The tetrah ydropyran molecule greatly increases the s o hbility of purine derivatives in organic solvents and provides a useful blocking group which can be readily used to prevent undesirable side reactions due to the presence of the imidazole hydrogen. Acid hydrolysis regenerates the purine.( 5 ) The synthetic route employed in the synthesis of N-methylalloxan and of N-phenylalloxan start~ nlth the appropriate monosubrtituted urea and cyano.cetic-corboxyl-C'~ acid to yield RNH-CONHC*OCHsCN, which undergoes ring closure in the pruence of

Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents

“…9H-purine (2) 30 p-TSA (0.01 g) was added to a solution of 6-chloropurine (0.15 g, 1 mmol) in dry THF at reflux. After 3,4-dihydro-2H-pyran (0.098 g, 1.18 mmol) was added and the mixture refluxed for 15 h. After cooling to ambient temparature the reaction mixture was treated with 1 mL 25% NH 4 OH and sitirred for 5 min.…”

“…The solution was evaporated in vacuo and treated with 25 mL EtOAc, washed with brine and water. The organic phase was dried over Na 2 SO 4 , the solvent was evaporated in vacuo, and recrystallized from hexane petroleum ether to yield 2 (220 mg; 95%): mp 69-71 °C (67-69 °C 30 …”

“…The N-9 position in the starting compound 6-chloropurine (1) was protected as the tetrahydropyran-2-yl (THP) derivative 2 30 by reacting 1 with the carbocation formed in situ from 3,4-dihydro-2H-pyran and catalytic amount of p-TSA in refluxing THF. We prepared the 6-(substituted phenyl)purines 3-9 by Suzuki coupling reaction.…”

6‐Substituted Purines as Inhibitors of 15‐Lipoxygenase; a Structure‐Activity Study

“…All measurements of 15-lipoxygenase activities were carried out in a Shimadzu UV-160A spectrophotometer (Shimadzu, Kyoto, Japan) at 20Ϫ22°C. Compounds available by literature methods: 1a and 1b [15], 1c, 7c and 8c [16], 2 and 7n [17], 4a and 4b [3], 7a, 7b, 8a and 8b [1], 7h [4], 7k [18], 7l, 7m and 9a [19].…”

“…The active compounds did not exhibit significant scavenging of the radical diphenylpicrylhydrazyl (DPPH) and we proposed that the purine derivatives were so-called non-antioxidant inhibitors; they exert their activity by a direct interaction with the enzyme. 15-LO has been implicated in oxidation of low-density lipoproteins (LDL), a process believed to be important for the development of atherosclerosis [5,6], as well as for instance in prostate cancer [7,8], and spontaneous abortions [9]. Even though the clinical importance of these effects in humans is currently not known, development of potent and selective inhibitors of 15-LO appears to be an important task.…”