High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries
| Autor: | Brett C. Bookser, Nicholas B. Raffaele |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Glycosylation
Time Factors Molecular Structure Trimethylsilyl Organic Chemistry Nucleosides Chemical synthesis chemistry.chemical_compound chemistry Triethanolamine Yield (chemistry) Databases Genetic medicine Structural isomer Organic chemistry Microwaves Trifluoromethanesulfonate Nucleoside medicine.drug |
| Zdroj: | The Journal of Organic Chemistry. 72:173-179 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo061885l |
| Popis: | The Vorbrüggen glycosylation reaction was adapted into a one-step 5 min/130 degrees C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl triflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base. |
| Databáze: | OpenAIRE |
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