High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries

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• 作者：Brett C. Bookser ; Nicholas B. Raffaele
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：January 5, 2007
• 年：2007
• 卷：72
• 期：1
• 页码：173 - 179
• 全文大小：142K
• 年卷期：v.72,no.1(January 5, 2007)
• ISSN：1520-6904

文摘

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The Vorbrüggen glycosylation reaction was adapted into a one-step 5 min/130 C microwave assistedreaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for theneutralization 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 librarysynthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogencontaining 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, twopyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yieldedsingle regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparableregioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yieldisolable 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 ofwhich 15 had not previously been accessed directly from glycosylation/deprotection of a readily availablebase.