Isoquinoline‐1‐Carboxylate as a Traceless Leaving Group for Chelation‐Assisted Glycosylation under Mild and Neutral Reaction Conditions

Abstract

Glycosyl isoquinoline‐1‐carboxylate was developed as a novel benchtop stable and readily available glycosyl donor. The glycosylation reaction was promoted by the inexpensive Cu(OTf)2 salt under mild reaction conditions. The copper isoquinoline‐1‐carboxylate salt was precipitated from the solution and thus rendered a traceless leaving group. Surprisingly, the proton from the acceptor was absorbed by the precipitated metal complex and the reaction mixture remained at neutral pH. The copper‐promoted glycosylation was also proven to be completely orthogonal to the gold‐promoted glycosylation, and an iterative synthesis of oligosaccharides from benchtop stable anomeric ester building blocks becomes possible under mild reaction conditions.

Glycosyl ortho-(1-phenylvinyl)benzoates versatile glycosyl donors for highly efficient synthesis of both O-glycosides and nucleosides

“…We envisioned that orthogonal one-pot synthesis of oligosaccharides based on glycosyl PVB could also be explored to streamline chemical synthesis of oligosaccharides in one-pot, whose sulfated derivatives exhibit significant proangiogenic activity 60 . It was noted that stepwise orthogonal glycosylation approach afforded tetrasaccharide 15 in only 39% overall yield 61 . Replacing the above acceptor 2c with the poor 4-OH acceptor 2b, tetrasacchaide 16 was still obtained in satisfactory 59% overall yield in one pot by successive coupling of TACI 10, ABz 11, PVB 12, and acceptor 2b (Fig.…”

Synthesis of Glycosyl Chlorides and Bromides by Chelation Assisted Activation of Picolinic Esters under Mild Neutral Conditions

“…In response to the potential transesterification side reactions, we recently reported isoquinoline-1-carboxylate (ISQ) as a readily available, traceless, and bulkier anomeric leaving group, which successfully blocks the attack of hydroxylic acceptors on the carbonyl carbon center (Scheme ). While screening potential copper­(II) sources for the activation of isoquinolinic esters, we discovered that using CuCl 2 produced no O -glycosides but instead led to the formation of the corresponding glycosyl chloride in high yield. The glycosyl halide was formed under conditions that were mild enough to facilitate inclusion of previously unavailable protecting groups that have low stability in acidic solutions.…”

“…The isoquinolinic ester was advantageous over the picolinic ester for the glycosylation reaction, because the carbonyl group in the latter could be attacked by the OH group in the glycosyl acceptor to form a transesterification product while no transesterification was observed for the former . We began our investigation by comparing the isoquinolinic esters and picolinic esters and their ability to produce the corresponding glycosyl chloride in order to examine potential differences in reactivity.…”

O-Glycosylation Enabled by N-(Glycosyloxy)acetamides

“…Glycosyl donor 17 was prepared according to the procedure for the preparation of 7 (0.62 g, 79%) as a white solid. mp: 94.3−95.8 °C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.72 (br s, 1H), 8.06−7.28 (m, 20H), 6.00 (t, J = 9.5 Hz, 1H), 5.75 (t, J = 9.2 Hz, 1H), 5.64 (t, J = 8.7 Hz, 1H), 5.20 (br s, 1H), 4.72 (d, J = 11.9 Hz, 1H), 4.54 (dd, J = 12.2, 4.6 Hz, 1H), 4.30−4.21 (m, 1H), 1.98 (s, 3H); 13 Phthalimidyl 2,3,4,6-Tetra-O-benzoyl-α-D-mannopyranoside (22). The same procedure for the synthesis of 19 was applied, yielding 22 (0.36 g, 79%) as a white solid.…”

“…Among various glycosyl donors, there is a class of glycosyl donors which could be activated with the assistance of vicinal exoanomeric-atom or remote functional-substituent on leaving group. Elegant studies on glycosyl donors such as n-pentenyl glycosides, 12 n-pentenyl esters, 13 glycosyl benzyl phthalates, 14 alkynoates, 15 glycosyl pentenoates, 16 glycosyl o-alkynylbenzoates, 11b 2-(2-propylsulfinyl)benzyl glycosides, 17 propargyl 1,2orthoesters, 18 o-(p-methoxyphenylethynyl)phenyl glycosides, 19 S-benzoxazolyl (SBox) glycosides, 20 S-thiazolinyl (STaz) glycosides, 21 and glycosyl isoquinoline-1-carboxylates, 22 were reported. These donors possess auxiliary activation functional groups such as alkenyl, alkynyl, SCN and heterocyclic substituents, and they could be easily activated by either an electrophilic reaction or a chelating reaction under mild conditions (Scheme 1a).…”