- High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
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The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate 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.
- Bookser, Brett C.,Raffaele, Nicholas B.
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p. 173 - 179
(2007/10/03)
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- A New Direct Glycosylation of Pyrimidine, Pyrazole, Imidazole and Purine Heterocycles via their N-tetrahydropyranyl (THP) Derivatives
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Pyrimidine, pyrazole, imidazole and purine N-tetrahydropyranyl (THP) derivatives have been converted in one-pot and in a regio- and stereo-selective manner into the corresponding β-D-2',3',5'-tri-O-benzoyl ribofuranosyl nucleoside derivatives on treatment with 1-β-acetyl-2',3',5'-tri-O-benzoyl-ribofuranose, hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCl), and trimethylsilyl triflate (TMST).
- Manfredini, Stefano,Baraldi, Pier Giovanni,Bazzanini, Rita,Guarneri, Mario,Simoni, Daniele
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p. 583 - 584
(2007/10/02)
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