Solvent Participation in a One‐Pot Glycosylation Strategy (SPOG)

Abstract

Solvent participation in a one-pot glycosylation strategy (SPOG) was developed on the basis of the low concentration b-selective glycosylation method. This strategy enables the production of a b-glycosidic bond in a one-pot oligosaccharide synthesis without or with minimal use of any C-2 participating function.Keywords: low concentration glycosylation; nitriles; one-pot process; reactivity-based reaction; solvent participation Oligosaccharide synthesis involves the coupling of carbohydrate units in a regio-and stereospecific manner. [1,2] This process can be accelerated by a onepot glycosylation strategy [3] and automated solidphase synthesis.[4] One-pot glycosylation refers to cascade coupling of three or more carbohydrate units in one shot.[5] A key element in these reactions is the stereochemical control of glycosidic bond formation, which often relies on traditional methods. A point in case is the use of neighbouring group participation for the construction of a 1,2-trans b-glycosidic bond. [6] However, such an approach requires the selective introduction of a C-2 participating function and it occasionally suffers from side reactions that decreases the yield of glycosylations. [7,8] Although alternative methods are available, only few of them are adapted to one-pot oligosaccharide synthesis. [9,10] Recently, a low concentration b-selective glycosylation (LCG) method was developed.[11] This method makes use of: (i) a CH 2 Cl 2 /CH 3 CN/EtCN solvent system; (ii) low substrate concentrations (10-15 mM); and (iii) low reaction temperature (À70 to À60 8C) to construct the 1,2-trans b-glycosidic bond without reliance on any C-2 participating function. A search in the literature revealed that the solvent effect on reactivity of glycosyl donors has been explored for onepot oligosaccharide synthesis, but the participation effect of an alkyl nitrile solvent on one-pot glycosylation has not been investigated. [12,13] This lack of information motivated us to develop a new one-pot glycosylation strategy on the basis of the LCG method. As the participation effect of an alkyl nitrile solvent is explored, we coin this approach as a solvent participation in one-pot glycosylation (SPOG) strategy.According to the order of solvent addition, two SPOG procedures were studied (Figure 1). In the first procedure, all glycosylation steps are performed under LCG conditions. As such, oligosaccharides with 1,2-trans b-glycosidic bonds are prepared (Figure 1 a). [10] In the second procedure, CH 2 Cl 2 and a conventional substrate concentration are employed for the first glycosylation step. Upon completion of this reaction, calculated amounts of CH 3 CN and EtCN are added to the mixture providing the LCG conditions for the next glycosylation reaction (Figure 1 b). The merit of the second procedure is to allow adjustment of the solvent mixture for the construction of a-and b-glycosidic bonds.Before exploiting the SPOG procedures, it was crucial to know if the LCG method would apply to nonthioglycoside donors. Thus, perbenzyl thiog...

Recent advances in reagent-controlled stereoselective/stereospecific glycosylation

“…As we discussed before, Mong et al applied DMF as an additive to control the selectivity in thioglycosyl donor successfully. Recently, they applied solvent effect in various glycosyl donors simultaneously and one-pot strategy to synthesize oligosaccharides [64]. DMF was also applied to control the selectivity of synthesizing α-and β-O-glycosyl serine conjugates with anomeric-protection-free glycosyl donors by Gin's group (Scheme 12) [61].…”

Modulating glycosylation with exogenous nucleophiles: an overview

“…79 With the glycosyl building blocks 94, 95, and 96 in hand, the protected tetrasaccharide core 100 was assembled in good 60% yield by the application of the low concentration one-pot glycosylation method (Scheme 20c). 80,81 The subsequent post-glycosylation modification and global deprotection of 100 concluded the first synthesis of the glycoglycerolipid 101 and two structural truncated analogues 102 and 103 for studies on immunological properties.…”

A general and convergent synthesis of diverse glycosylphosphatidylinositol glycolipids

“…40 Glycosylation with per-O-benzylated galactosyl trichloroacetimidate 41 using Pd(CH 3 CN) 4 (BF 4 ) 2 as a catalyst in dichloromethane or acetonitrile, however, suffered from low conversion. With the same set of coupling partners using TMSOTf as the activating reagent at low temperatures in a 1 : 2 : 1 CH 2 Cl 2 -MeCN-EtCN solvent mixture, 42 reactions also proceeded sluggishly and signicant production of the rearranged imidate side product was observed. In an attempt to eliminate the possibility of glycosylating agent rearrangement per-O-benzylated galactosyl phosphate 45 was employed.…”