An Efficient Approach to the Synthesis of Nucleosides: Gold(I)‐Catalyzed N‐Glycosylation of Pyrimidines and Purines with Glycosyl ortho‐Alkynyl Benzoates

Abstract

Überredet mit Gold: Die Titelreaktion liefert in Gegenwart von [Ph3PAuNTf2] (Tf=Trifluormethansulfonyl) bequem und hoch regioselektiv die jeweiligen Nucleoside (siehe Schema). Sogar Purinderivate können umgesetzt werden, weil die milden Bedingungen den Einsatz von Schutzgruppen ermöglichen, die mit den gängigen N‐Glycosylierungsbedingungen inkompatibel sind.

Characterization of the Isochromen‐4‐yl‐gold(I) Intermediate in the Gold(I)‐Catalyzed Glycosidation of Glycosyl ortho‐Alkynylbenzoates and Enhancement of the Catalytic Efficiency Thereof

“…Our previous puzzles, that the gold(I)-catalyzed glycosylation reaction could not proceed in the present of a base [1c] and that addition of TfOH could accelerate greatly the reaction rate, [6] have thus been solved. Moreover, a solution to lower the catalyst loading in the gold(I)-catalyzed glycosylation has emerged.…”

“…[1][2][3][4][5][6] Moreover, the unprecedented activation mechanism has endowed this protocol with unique merits, including 1) the absence of competitive nucleophilic species (which usually occur in the leaving entity or promoter in classical glycosylation reactions), which enables glycosylation-initiated polymerization of tetrahydrofuran to proceed smoothly; [3] 2) the lack of deteriorative electrophilic species (such as the soft Lewis acidic species used as promoters in classical glycosylation reactions), which enables flavonol 3-OH derivatives vulnerable toward electrophiles to be glycosylated efficiently;…”

Characterization of the Isochromen‐4‐yl‐gold(I) Intermediate in the Gold(I)‐Catalyzed Glycosidation of Glycosyl ortho‐Alkynylbenzoates and Enhancement of the Catalytic Efficiency Thereof

“…We have recently developed a new glycosylation protocol with glycosyl ortho ‐alkynylbenzoates as donors and a gold(I) complex (e.g., [Ph 3 PAuOTf], OTf=O 3 SCF 3 ) as catalyst 1. The power and versatility of this gold(I)‐catalyzed glycosylation method have been demonstrated in the effective construction of a wide variety of glycosidic linkages and the total synthesis of complex oligosaccharides and glycoconjugates 1–6. Moreover, the unprecedented activation mechanism has endowed this protocol with unique merits, including 1) the absence of competitive nucleophilic species (which usually occur in the leaving entity or promoter in classical glycosylation reactions), which enables glycosylation‐initiated polymerization of tetrahydrofuran to proceed smoothly;3 2) the lack of deteriorative electrophilic species (such as the soft Lewis acidic species used as promoters in classical glycosylation reactions), which enables flavonol 3‐OH derivatives vulnerable toward electrophiles to be glycosylated efficiently;4 and 3) the mild and nearly neutral conditions, which allow the extremely acid‐labile aglycones, such as the N ‐Boc‐protected purine derivatives (Boc= tert ‐butoxycarbonyl) and dammarane derivatives, to be glycosylated effectively 5.…”

“…Moreover, the unprecedented activation mechanism has endowed this protocol with unique merits, including 1) the absence of competitive nucleophilic species (which usually occur in the leaving entity or promoter in classical glycosylation reactions), which enables glycosylation‐initiated polymerization of tetrahydrofuran to proceed smoothly;3 2) the lack of deteriorative electrophilic species (such as the soft Lewis acidic species used as promoters in classical glycosylation reactions), which enables flavonol 3‐OH derivatives vulnerable toward electrophiles to be glycosylated efficiently;4 and 3) the mild and nearly neutral conditions, which allow the extremely acid‐labile aglycones, such as the N ‐Boc‐protected purine derivatives (Boc= tert ‐butoxycarbonyl) and dammarane derivatives, to be glycosylated effectively 5. 6…”

“…Our previous puzzles, that the gold(I)‐catalyzed glycosylation reaction could not proceed in the present of a base1c and that addition of TfOH could accelerate greatly the reaction rate,6 have thus been solved. Moreover, a solution to lower the catalyst loading in the gold(I)‐catalyzed glycosylation has emerged.…”