Tetrabutylammonium fluoride-assisted rapid N9-alkylation on purine ring: application to combinatorial reactions in microtiter plates for the discovery of potent sulfotransferase inhibitors in situ.
Tremendous efforts have been invested in the synthesis of purine libraries due to their importance in targeting various enzymes involved in different diseases and cellular processes. The synthesis of N9-alkylated purine scaffolds relied mostly on Mitsunobu conditions with a variety of alcohols or strong basic conditions with different organic halides. A more reliable and efficient way for the synthesis of N(9)-alkylated purine scaffolds is reported. This method uses tetrabutylammonium fluoride (TBAF) to assist such chemistry. In many cases, the reactions were completed within 10 min and gave the desired product in high yield and selectivity. Moreover, these mild reaction conditions permitted its use in combinatorial reactions in microtiter plates followed by in situ screening for the discovery of potent sulfotransferase inhibitors.
Brik
Ashraf
A
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Wu
Chung-Yi
CY
Best
Michael D
MD
Wong
Chi-Huey
CH
D000478:Alkylation; D020650:Combinatorial Chemistry Techniques / Q000295:instrumentation*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011687:Purines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D011687:Purines; D000644:Quaternary Ammonium Compounds; C009405:tetrabutylammonium; D015238:Sulfotransferases; C030985:purine