Synthesis and Cytostatic Activity of Substituted 6-Phenylpurine Bases and Nucleosides:  Application of the Suzuki−Miyaura Cross-Coupling Reactions of 6-Chloropurine Derivatives with Phenylboronic Acids

Abstract

The Suzuki-Miyaura reaction of protected 6-chloropurine and 2-amino-6-chloropurine bases and nucleosides with substituted phenylboronic acids led to the corresponding protected 6-(substituted phenyl)purine derivatives 6-9. Their deprotection yielded a series of substituted 6-phenylpurine bases and nucleosides 10-13. Significant cytostatic activity (IC(50) 0.25-20 micromol/L) in CCRF-CEM, HeLa, and L1210 cell lines was found for several 6-(4-X-substituted phenyl)purine ribonucleosides 12 (X = H, F, Cl, and OR), while the 6-phenylpurine and 2-amino-6-phenylpurine bases 10 and 11, as well as 2-amino-6-phenylpurine ribosides 13, were entirely inactive against these cell lines.

Simple method for fast deprotection of nucleosides by triethylamine-catalyzed methanolysis of acetates in aqueous medium

“…Therefore, multi-step synthesis frequently requires the introduction of protective groups and their subsequent removal. [10][11][12][13] Typical methods for removing the acetate groups in acetylated nucleosides rely on the use of methanolic ammonia, [14][15][16] metal alkoxides, [16][17][18] and hydrolytic enzymes, 19 often in good yields. Although all of the above procedures offer certain benefits, they also suffer from drawbacks such as long reaction times, high costs, the use of unstable or noxious reagents, harmful conditions, and the need for special safety precautions, which represent major disadvantages due to environmental concerns.…”

Synthesis of Some Novel Thiocyanotopurine Derivatives and Investigation of Their Antimicrobial Activity and DNA Interactions

“…chromatography to provide the compounds 2-10 in moderate to good yields. The structure of compounds 2-10 were confirmed by FT-IR, 1 H-NMR, 13 C-NMR and MS spectra or elemental analyses. The IR spectra of the synthesized compounds exhibited a band in the region of 2164-2181 cm −1 which can be assigned to the characteristic band of stretching vibrations of CN group.…”

“…12) Replacement of the oxygen atom at position 6 in guanine and in hypoxanthine with sulfur gave clinically widely used anticancer drugs, thioguanine (NSC752) and 6-mercaptopurine (NSC755). 13) Structurally related nucleoside sulfinosine [2-amino-9-(β-D-ribofuranosyl)purine-6-sulfinamide] also exhibited unique antitumor properties. 14) 6-Methylmercapto-9-(β-D-ribofuranosyl)purine is one of the most potent inhibitors of de novo purine synthesis.…”

“…The disappearance of band at 3443 cm −1 (-N-H stretching frequency) is good evidence for the structure of the compounds 2-10. 13 C-NMR spectra showed a characteristic peak at δ 106 ppm for CN group.…”

Synthesis of Fluorine-Containing 6-Arylpurine Derivatives <i>via</i> Cp*Co(III)-Catalyzed C–H Bond Activation

“…6-Arylpurines have anti-mycobacterial, anti-hepatitis C virus (HCV), and cytostatic activities, [35][36][37][38] and the purine moiety works as a good directing group for C-H bond activation with transition metal catalysts. [39][40][41][42][43][44][45][46][47][48][49] During the course of our investigation of Cp*Co(III)-catalysis, 47,48,[50][51][52][53][54] we became interested in catalytic C-H bond functionalization of 6-arylpurine derivatives, and recently reported C-H allylation 47) and trifluoromethylthiolation 48) reactions.…”