Monosaccharide acceptor

Although aliphatic alcohols are typically poor acceptors in the Mitsunobu-type glycosylation, Szarek and coworkers have highlighted one advance to this end [95]. For the triphenylphosphine and diethylazodicarboxylate promoted glycosylation of a monosaccharide acceptor, the addition of mercuric bromide is necessary to promote the reaction. For example, the (1,6)-disaccharide 44 was obtained in 80% yield using this modified Mitsunobu protocol. Unlike previous examples with phenol or N-acceptors, preactivation of the hemiacetal donor was performed for 10 min at room temperature prior to addition of the aliphatic alcohol nucleophile. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

Glycosyl esters with remote functionality constitute a relatively new class of O-carbonyl glycosyl donors, which fulfill the prospect of mild and chemoselective activation protocols (Scheme 3.22). For example, Kobayashi and coworkers have developed a 2-pyridine carboxylate glycosyl donor 134 (Y = 2-pyridyl), which is activated by the coordination of metal Lewis acid (El+) to the Lewis basic pyridine nitrogen atom and ester carbonyl oxygen atom [324]. In the event, 2-pyridyl (carbonyl) donor 134 and the monosaccharide acceptor were treated with copper(II) triflate (2.2 equiv) in diethyl ether at —50 °C, providing the disaccharide 136 in 70% (a P,... 

Fig. 13. Universal building block 18, photo linker resin 19, and CSPOS sequence to the fully benzylated, resin-bound monosaccharide acceptors 21, 22, 23, and 24. Reactions (a) loading, (b) transesterification, (c) TBDPS cleavage, (d) alkylation, (e) ring opening [—> 6-OH], (f) ring opening [—> 4-OH], (g) acidic TBDPS cleavage, (h) neutral/acidic benzylation.

Fig. 14. CSPOS sequence to disaccharides 25, 26, and 27 via the fully benzylated, resin-bound monosaccharide acceptors 21,22, and 23. Reagents and conditions (a) DMTST, 18 (2.0 equiv.), MS 4 A, CH2C12, two runs.

Employing glycosyl donors of the above type and a simple monosaccharide acceptor such as methyl 2-0-benzyl-4,6-0-benzylidene-a-D-mannopyranoside or the... 

FIGURE 8.4 a-Selective glycosylation of monosaccharide acceptors with KDO using the microfluidic method. 

KDO glycosylations using monosaccharide acceptors were also examined [22], Combination of TfOH as catalyst and CH3CN as solvent gave better results than other catalysts (TMSOTf, TBSOTf) and solvents (CPME, CH2C12, toluene). The a selectivity was increased under microflow conditions, though the yields between batch (86%, a/p=85/15) and microflow conditions (83%, a/p=92/8) were comparable (Fig. 8.4). 

TentaGel-N, linked via the succinoyl linker to a monosaccharide acceptor was utilized using trichloroacetimidate chemistry to prepare disaccharides [34] and trisaccharides [78]. It was observed that TentaGel is slightly unstable under the acidic conditions required by trichloroacetimidate chemistry [78], most likely due to the acid sensitivity of PEG [79]. No similar sensitivity was observed in similar applications employing Argogel [78]. 

Scheme 5. Solid-phase enzymatic synthesis of a Lewis tetrasaccharide using a linker of 71 atoms between the monosaccharide acceptor and the Sepharose matrix. Reagents i) 1. cacodylate buffer pH 7.5, 5 mM MnCb, a-lactalbumin, GT, UDP Gal (3 eq.), CIAP, 37 °C, 5 days 2. cacodylate buffer pH 7.35, 0.1% triton X-100, ST3, CMP-NeuAc (2.5 eq.), 3 him MnCb, 0.02% NaNj, 35 °C, 5 days 3. cacodylate buffer pH 6.5, 5 mM MnCL, FT, GDP-Fuc (4 eq.), 37 °C, 5 days ii) 1. DTT, 0.1 M phosphate buffer 2. BioGel P-2, 57% from 14.

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