Experiments on the synthesis of pyrazine nucleosides

Abstract

Pyrazine nucleosides were prepared by condensation of acylglycosyl halides with trirnethylsilyloxypyrazines in benzene i n the presence of si her pe rc hl orate. Reaction of 2,3,4,6 -tetra -0 -acet \/ la-Dg I ucopyra nosy l bromide (1 ) with 2,3-bis(trimethylsilyloxy) pyrazine (2) gave 1.4-dihydro-I ,4-bis-(2,3,4,6-tetra-0-acetyl-@-~-glucopyranosyl)pyrazine-2,3-dione ( 3 ) . Similar reactions of 2,3.5-tri-O-benzoyl-~-ribofuranosyl chloride (4) with the pyrazine ( 2 j and 1 -benzyl-3-trirnethylsilyloxypyrazine-2(1H)-one ( I 4) afforded 1,4-dihydro-l,4-bis-($-~ribofuranosyl)pyrazine-2,3-dione (6) and 1 -benzyl-l,4-dihydro-4-(~-~-ribofuranosyl)pyrazine-2,3-dione (1 6). respectively, via their 2'.3',5'-tri-O-benzoates [ ( 5) and (1 5)]. 1 -Benzyl-l,4-dihydropyrazine-2,3-dione (1 2) w a s prepared by acid-catalysed cyclization of N-benzyl-N'-(2,2-dimethoxyethyl)oxamide ( 9), which w a s obtained by condensation of ethyl N-(2,2-dimethoxyethyl)oxamate (7) with benzylamine.of Chemistry, Queen Elizabeth College, Campden Hill Road, London W8 7AH PVRAZINE nucleosides are analogues of the naturally occurring pyrimidine nucleosides. Under certain conditions unnatural nucleosides may bc incorporated into RNA which will block cell division and growth. Such nucleosides are potential anti-tumour agents since tumour cells metabolize faster than normal cells and tend to incorporate antagonistic compounds prefer-entia1ly.l In attempts to synthesize a pyrazine analogue (17) of uridine, we have isolated the pyrazine nucleosides (6) and ( 16), which gave negative results when tested against Ridgeway osteogenic sarcoma and L.1210.2 showed that direct glucosidation of the silver or mercury salt of pyrazine-2 (1H) -one furnished the O-glucoside and

Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

“…A modification of the Cheeseman pyrazinedione synthesis was employed for P2 subunit production (Scheme 3). 29,25 Addition of aminoacetaldehyde dimethylacetal to oxamate 42 25 afforded the cyclization precursor 43. Refluxing oxamide 43 in acetic acid, with a catalytic amount of HCl, affected cyclization to the crude pyrazinedione 44.…”

Development of a Scaleable Synthesis of a 3-Aminopyrazinone Acetamide Thrombin Inhibitor

“…Preparation of the Pyrazinone 4. The preparation of ethyl 2-(2,3-dioxo-1,4-dihydropyrazinyl)acetate 4 was based on the methods of both Cheeseman and Fleitz …”

2(1H)-Pyrazinones from acyclic building blocks: methods of synthesis and further derivatizations

“…The key steps of this strategy involve the formation of the C-3-N-4 bond and a cyclization between N-1 and C-6. 68 This synthetic route starts with diethyl oxalate reacting with an equimolar quantity of 2,2-dimethoxyethylamine to afford oxamate 44 that is converted with benzylamine into the corresponding N-benzyl-N ′ -(2,2-dimethoxyethyl)oxamide 45 (Scheme 10a). This N-1-protected oxamide undergoes cyclization under reux in acetic acid with a catalytic amount of HCl.…”

“…The key steps of this strategy involve the formation of the C-3–N-4 bond and a cyclization between N-1 and C-6. 68…”