Stereochemical Features of Lewis Acid-Promoted Glycosidations Involving 4‘-Spiroannulated DNA Building Blocks

• Published in: Journal of organic chemistry 2004-10, Vol.69 (22), p.7442-7447
• Main Authors: Paquette, Leo A, Seekamp, Christopher K, Kahane, Alexandra L, Hilmey, David G, Gallucci, Judith
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemistry; Carbohydrates. Nucleosides and nucleotides; Catalysis; Chemistry; Crystallography, X-Ray; DNA - chemistry; Exact sciences and technology; Glycosides - chemistry; Models, Molecular; Molecular Conformation; Molecular Mimicry; Molecular Structure; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Preparations and properties; Spiro Compounds - chemistry; Stereoisomerism; Tin Compounds - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048904g

Tin tetrachloride-catalyzed glycosidation of persilylated nucleobases with acetate donor 6 in CH2Cl2 solution followed by deprotection gave rise very predominantly to α-spironucleosides. These stereochemical assignments stem from the determination of NOE interactions and an X-ray crystallographic analysis of the latter product. Computational studies revealed that these results are consistent with the fact that the C5‘ substituent shields the β-face of the oxonium ion involved in the coupling reaction while the C3‘ substituent is projected away from the α-underside. Attack from the more open direction is therefore kinetically favored. Entirely comparable calculations suggested that donor 19 should behave comparably. Experimentation involving this donor gave results consistent with this model although more equitable α/β spironucleoside product ratios were seen when acetonitrile was employed as the reaction medium.