Synthesis of C-aryl-nucleosides and O-aryl-glycosides via cuprate glycosylation.
2'-Deoxy-C-aryl-nucleosides have found increasing importance in studying DNA-DNA and DNA-protein interactions, as unnatural DNA-base pairs, and as oligonucleotide based fluorophores. Access to the required C-aryl-nucleosides is provided by several glycosylation methods. Though useful in many cases, these methods often have drawbacks such as low yields or low economic efficiency. The necessity for intensive optimization of the reaction conditions and/or the use of hazardous and toxic reagents can render C-glycosylation reactions cumbersome. Herein we describe a robust and highly efficient C-glycosylation method. It is shown that aryl cuprates of the Normant-type reliably react with Hoffer's chlorosugar to deliver C-aryl-nucleosides in up to 93% yield. This method may substitute for the previously employed coupling with organocadmium or -zinc species. Peculiar reactivities are reported for C-glycosylation of Gilman-type aryl cuprates which required substantial arene-specific optimization. Interestingly, the glycosylation of Gilman cuprates was found to provide access not only to C-aryl-nucleosides but also to O-aryl-glycosides. The reactions of Gilman cuprates with Hoffer's chlorosugar 1 in the presence of oxygen provided the coresponding O-aryl-2'-deoxyribosides in up to 87% yield without concomitant C-glycosylation.
Hainke
Sven
S
Humboldt-Universität zu Berlin, Institut für Chemie, Brook-Taylor Strasse 2, D-12489, Berlin, Germany.
Singh
Ishwar
I
Hemmings
Jennifer
J
Seitz
Oliver
O
D002241:Carbohydrates / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry*; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D002241:Carbohydrates; D006027:Glycosides; D009705:Nucleosides; D009942:Organometallic Compounds; D003300:Copper