CARB 6 |
| The 2'- and 3'-hydroxyls play important roles in nucleic acid chemistry. The 3'-OH is the leaving group in cleavage of RNA, protein synthesis, and phosphate ester exchange reactions. 2'-OH acts as nucleophile in the cleavage of RNA, and participation of 2'-OH in the catalysis of peptide bond formation by peptidyl transfer reaction has been reported. Kinetic isotope effect analysis provides detailed information about the transition state of a chemical reaction. To apply this method toward the vicinal hydroxyl groups of the ribose sugar requires the efficient synthesis of 2'- and 3'-18O labeled nucleosides. Here we report the syntheses of 2'- and 3'-18O-adenosine with 18O enrichment of >90%. 18O-Propionic acid was prepared by acidic hydrolysis of propionitrile. The 3'-18O-adenosine was first prepared according to a reported approach, with an improvement in the regioselectivity for 18O incorporation by addition of an imidazolium salt. A new route via sequential SN2-SN2 reactions has been developed to provide 3'-18O-adenosine in 13 steps, with high efficiency in 18O incorporation. |
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Nucleosides, Nucleotides and Oligonucleotides
9:00 AM-11:40 AM, Sunday, 10 September 2006 Hilton San Francisco -- Yosemite C, Oral
Division of Carbohydrate Chemistry |