Progress in the Chemical Synthesis of 2-Deoxy-glycosides

Abstract

2-Deoxy-glycosides are monosaccharides in which the hydroxyl group at C-2 is replaced with a hydrogen atom. They exist widely in natural products and show various bioactivity. The recent advances in organic synthesis of 2-deoxy-glycosides are summarized mainly focusing on direct etherification, direct glycosidic bond formation, temporary protecting groups, synthesis from non-sugar and so on. Keywords 2-deoxy-glycosides; oligosaccharides; chemosynthesis methodology

A Glycal Approach to the Synthesis of Pregnane Glycoside P57

“…[13] These poor β-selectivities could be attributed to the α-favored anomeric effect as well as the incapable of participation from the C2 or C3 substituents of the cymarosyl donors. [21][22][23][24][25][26][27][28] Glycals are capable donors for the synthesis of 2-deoxyglycosides under the action of triphenylphosphine hydrobromide (TPHB). [29][30][31] In McDonald and Reddy's synthesis of digitoxin, the glycosylation of the steroid aglycone was achieved with a trisaccharide glycal in the presence of TPHB (82%, β/α＝3 : 2).…”

Regioselective Direct Difunctionalization of Glycals: Convenient Access to 2‐Deoxyglycoconjugates Mediated by Tetra‐n‐butylammonium Iodide/Sodium Periodate

“…In view of appreciable medicinal values, the synthesis of 2-deoxyglycosides in stereo and regioselective manners continues to attractc onsiderable attention and remains an ontrivial task. [3,4] Traditionally,2 -deoxy-a-glycosides are synthesized in at wo-step process;c hemical glycosylation employing 2-deoxy-2-haloglycopyranosyl acetates as donors, [5] and post-glycosylation reductiveelimination or dehalogenation from the C2 position. [6] On the other hand, the oxidative glycosylation of glycals with acceptors in the presence of electrophilic iodine( iodonium ion, I + )r eagents such as molecular iodine in combination with Cu salts, [7a,b] N-iodosuccinimide (NIS), [7c,d] or iodonium-di-sym-collidine perchlorate (IDCP) [7e,f] provides 2-deoxy-2-iodoglycosides with 1,2-trans-diaxial, amanno as major product.…”

2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

“…1a). 3,4 Hence, the stereochemistry control in glycosylation is one of the central topics and difficult tasks in carbohydrate chemistry, [5][6][7] particularly in the synthesis of -configured 2-deoxy-and 2-azido-2-deoxy-glycosides, [8][9][10][11][12][13][14] which are important structural components or synthetic precursors of numerous drugs and bioactive molecules such as digoxin, landomycin, hyaluronic acid, and lipid A. 15,16 Owing to the anomeric effect, glycosylation with 2-deoxy-or 2-azido-2-deoxy-glycosyl donors tends to give -glycosides as the major product.…”

“…15,16 Owing to the anomeric effect, glycosylation with 2-deoxy-or 2-azido-2-deoxy-glycosyl donors tends to give -glycosides as the major product. 3,4,10 Thus, extensive studies have been devoted into the construction of the more challenging -glycosides, [8][9][10][11][12][13][14] employing donors/intermediates via SN2/SN2-like pathway, [17][18][19][20] -face steric hindrance, [21][22][23][24] 2-halo participation, 25,26 -glycosyl lithium, 27,28 triflate acceptor, 29 2,3-anhydrosugar, 30 de novo synthesis, 31,32 oxidative activation with I2, 33 etc. However, their application in complex carbohydrate synthesis was usually case by case, hampered by narrow substrate scope, low efficiency, tedious steps, or harsh conditions.…”