A General and Efficient Synthesis of Pyridin-2-yl C-Ribonucleosides Bearing Diverse Alkyl, Aryl, Amino, and Carbamoyl Groups in Position 6

• Published in: Journal of organic chemistry Vol. 75; no. 2; pp. 442 - 449
• Main Authors: Štefko, Martin, Slavětínská, Lenka, Klepetářová, Blanka, Hocek, Michal
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 15.01.2010; Amer Chemical Soc
• Subjects: Alkanes - chemical synthesis; Alkanes - chemistry; Carbamates - chemical synthesis; Carbamates - chemistry; Catalysis; Chemistry; Chemistry, Organic; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy; Molecular Structure; Monosaccharides - chemical synthesis; Monosaccharides - chemistry; Palladium - chemistry; Physical Sciences; Ribonucleotides - chemical synthesis; Ribonucleotides - chemistry; Science & Technology; Structure-Activity Relationship; POLYMERASE RECOGNITION; PURINE NUCLEOSIDE PHOSPHORYLASE; DNA; GENETIC ALPHABET; BIOLOGICAL EVALUATION; MODULAR SYNTHESIS; OPTIMIZATION; UNNATURAL BASE-PAIR; NICOTINAMIDE ADENINE-DINUCLEOTIDE; PALLADIUM-CATALYZED AMINATION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo902313g

An efficient and practical methodology of preparation of 6-substituted pyridin-2-yl C-ribonucleosides was developed. A one-pot two-step addition of 2-lithio-6-bromopyridine to TBS-protected ribonolactone followed by acetylation gave 1β-(6-bromopyridin-2-yl)-1-O-acetyl-2,3,5-tri-O-(tert-butyldimethylsilyl)-d-ribofuranose in high yield. Its reduction with Et3SiH and BF3·Et2O afforded the desired TBS-protected 6-bromopyridine C-ribonucleoside as pure β-anomer in good overall yield of 63%. This intermediate was then subjected to a series of palladium catalyzed cross-coupling reactions, aminations and aminocarbonylations to give a series of protected 1β-(6-alkyl-, 6-aryl-, 6-amino-, and 6-carbamoylpyridin-2-yl)-C-ribonucleosides. Deprotection of silylated nucleosides by Et3N·3HF gave a series of title free C-ribonucleosides (12 examples).