Dimetalation of pyrazines. a one-pot synthesis of multisubstituted pyrazine C-nucleosides.
As a part of our efforts to pursue direct, convergent, and concise methodologies for the synthesis of pyrazine C-nucleosides, we have successfully established a sequential dilithiation-addition method, which allows one to introduce two different functional groups to a pyrazine ring in a one-pot fashion. 2,6-Dichloropyrazine was dilithiated at -100 degrees C and then allowed to react with an electrophile, such as bromine, iodine, or disulfides, followed by a reaction with a protected ribonolactone to afford C-nucleosides. After reduction and deprotection, tetrasubstituted pyrazine C-nucleosides, including 2,6-dichloro-3-iodo-5-(beta-D-ribofuranosyl)pyrazine and 2-bromo-3,5-dichloro-6-(beta-D-ribofuranosyl)pyrazine, were obtained. A tandem reaction sequence occurred when disulfides were used, resulting in the formation of 5,6-bis-methylthio-2-chloro-3-(beta-D-ribofuranosyl)pyrazine and 6-(beta-D-ribofuranosyl)-2,3,5-tris-phenylthiopyrazine.
Liu
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W
Department of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry, College of Literature, Science, and the Arts, The University of Michigan Ann Arbor, Michigan 48109, USA.
Wise
D S
DS
Townsend
L B
LB
D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011719:Pyrazines; D011741:Pyrimidine Nucleosides