13877-76-4Relevant academic research and scientific papers
Identification and Characterization of Enzymes Catalyzing Pyrazolopyrimidine Formation in the Biosynthesis of Formycin A
Ko, Yeonjin,Wang, Shao-An,Ogasawara, Yasushi,Ruszczycky, Mark W.,Liu, Hung-Wen
, p. 1426 - 1429 (2017)
Genome scanning of Streptomyces kaniharaensis, the producer of formycin A, reveals two sets of purA, purB, purC, and purH genes. The Pur enzymes catalyze pyrimidine assembly of purine nucleobases. To test whether enzymes encoded by the second set of pur genes catalyze analogous transformations in formycin biosynthesis, formycin B 5′-phosphate was synthesized and shown to be converted by ForA and ForB to formycin A 5′-phosphate. These results support that For enzymes are responsible for formycin formation.
Identification of the C-Glycoside Synthases during Biosynthesis of the Pyrazole-C-Nucleosides Formycin and Pyrazofurin
Ren, Daan,Wang, Shao-An,Ko, Yeonjin,Geng, Yujie,Ogasawara, Yasushi,Liu, Hung-wen
, p. 16512 - 16516 (2019)
C-Nucleosides are characterized by a C?C rather than a C?N linkage between the heterocyclic base and the ribofuranose ring. While the biosynthesis of pseudouridine-C-nucleosides has been studied, less is known about the pyrazole-C-nucleosides such as the formycins and pyrazofurin. Herein, genome screening of Streptomyces candidus NRRL 3601 led to the discovery of the pyrazofurin biosynthetic gene cluster pyf. In vitro characterization of gene product PyfQ demonstrated that it is able to catalyze formation of the C-glycoside carboxyhydroxypyrazole ribonucleotide (CHPR) from 4-hydroxy-1H-pyrazole-3,5-dicarboxylic acid and phosphoribosyl pyrophosphate (PRPP). Similarly, ForT, the PyfQ homologue in the formycin pathway, can catalyze the coupling of 4-amino-1H-pyrazole-3,5-dicarboxylic acid and PRPP to form carboxyaminopyrazole ribonucleotide. Finally, PyfP and PyfT are shown to catalyze amidation of CHPR to pyrazofurin 5′-phosphate thereby establishing the latter stages of both pyrazofurin and formycin biosynthesis.
Nucleolipids of the Nucleoside Antibiotics Formycins A and B: Synthesis and Biomedical Characterization Particularly Using Glioblastoma Cells
Rosemeyer, Helmut,Knies, Christine,Hammerbacher, Katharina,Bender, Eugenia,Bonaterra, Gabriel A.,Hannen, Ricarda,Bartsch, J?rg W.,Nimsky, Christopher,Kinscherf, Ralf
, (2019/04/08)
Two lipophilic derivatives of formycin A (1) and formycin B (5) carrying an O-2′,3′-(ethyl levulinate) ketal group have been prepared. These were base-alkylated at N(1) (for 1) and N(1) and N(6) (for 5) with both isopentenyl and all-trans-farnesyl residues. Upon the prenylation, side reactions were observed, resulting in the formation of nucleolipids with a novel tricyclic nucleobase (→4a, 4b). In the case of formycin B, O-2′,3′-(ethyl levulinate) (6) farnesylation gave the double prenylated nucleolipid 7. All new compounds were characterized by 1H-, 13C-, UV/VIS and fluorescence spectroscopy, by ESI-MS spectrometry and/or by elemental analysis. Log P determinations between water and octanol as well as water and cyclohexane of a selection of compounds allowed qualitative conclusions concerning their potential blood-brain barrier passage efficiency. All compounds were investigated in vitro with respect to their cytotoxic activity toward rat malignant neuroectodermal BT4Ca as well as against a series of human glioblastoma cell lines (GOS 3, U-87 MG and GBM 2014/42). In order to differentiate between anticancer and side effects of the novel nucleolipids, we also studied their activity on PMA-differentiated human THP-1 macrophages. Here, we show that particularly the formycin A derivative 3b possesses promising antitumor properties in several cancer cell lines with profound cytotoxic effects partly on human glioblastoma cells, with a higher efficacy than the chemotherapeutic drug 5-fluorouridine.
C-Nucleoside Studies. Part 17. The Synthesis of 3(5)-Carbamoyl-5(3)-β-D-ribofuranosylpyrazole (4-Deoxypyrazofurin) and 4-Amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole
Buchanan, J. Grant,Saxena, Naveen K.,Wightman, Richard H.
, p. 2367 - 2371 (2007/10/02)
4-Amino-3(5)-cyano-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (10) was converted into the diazopyrazole (11) by treatment with nitrous acid.On photolysis in aqueous dioxane using visible light compound (11) gave 3(5)-cyano-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (12) which formed the corresponding amide (13) (75percent) with alkaline hydrogen peroxide.Deprotection of compound (13) with methanolic ammonia afforded 3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (4) (74percent), the 4-deoxy analogue of pyrazofurin (3). 3(5)-Cyano-4-nitro-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (1) reacted with dihydropyran and toluene-p-sulphonic acid to give the N-tetrahydropyranyl) derivative (21) (66.5percent).Hydrolysis of the nitrile group of compound (21), using alkaline hydrogen peroxide, afforded the amide (22) (71percent) which was deprotected to give 3(5)-carbamoyl-4-nitro-5(3)-β-D-ribofuranosylpyrazole (23) (83percent).Catalytic reduction of compound (23) gave 4-amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (5) (83percent) which could be converted into formycin B (24) (69percent).
Pyrazolopyrimidine Nucleosides. 9. Studies of the Isomeric N-Methylformycins
Lewis, Arthur F.,Townsend, Leroy B.
, p. 2817 - 2822 (2007/10/02)
The syntheses of 4-methylformycin (7) and 6-methylformycin (8) are described.Structural assignements if 7 and 8 were based on UV, 1H NMR, and 13C NMR data.N-7-Methylformycin (9) was resynthesized by an alternative route and comparisons of the physicochemical properties of all five of the mono-N-methylformycins are presented. 6-Methylformycin (8) was found to be unstable in aqueous solution yielding three products, formycin B (2), N-7-methylformycin (9), and 6-methylformycin B (10). 6-Methylformycin B (10), 4-methylformycin B (11), and 1-methylformycin B (12) were prepared by a reaction of nitrosyl chloride with 8, 7, and 1-methylformycin (3), respectively.
