Sialosides acceptor

BF3-OEt2 Unnatural P-sialoside derivatives are produced preferentially by using O-acetylated glycosyl fluoride donor and BF3-OEt2 as the promoter. When P-sialyl fluoride derivative 28 was reacted with acceptor 22 in the presence of BF3-OEt2 in dichloromethane, the P-sialoside 28 was obtained in a mixture of anomers (a/p 17/83) (Scheme 2.11) [44],... 

An efficient a-sialylation that took advantage of the highly reactive sialyl donors having C5 cyclic imides, especially phthalimide (NPhth), by virtue of the fixed-dipole moment effects, was also reported [42], For example, the use of the sialyl donor 4 and acceptor 6 at -78°C supplied the sialoside 7 as a only with 92% yield on 50 mg scale. The scale-up in batch process, however, significantly decreased the yield and stereoselectivity. This decrease in sialylation efficiency might be a result of... 

Efficient activation of the N-acetylated sialyl donor required l.Oequiv. of the Lewis acid under -78°C, giving the disaccharide 16 in 77% yield with excellent a selectivity (a/p=96/4, Table 8.2, entry 1). The conditions in entry 1 were reproducible under the microfluidic conditions (entry 2, 89% yield, a/p=94/6). Because the excess donor 15 inhibited the purification of sialoside 16 from the glycal by-product due to similar polarities on silica gel, the ratio between the donor and the acceptor... 

As depicted in O Scheme 36 [106], the results of glycosylations of the primary hydroxyl of glucosyl acceptor 22 with A-Troc, A-TFAc, and AA -diacetyl sialyl donors (104,102, and 94) promoted by NIS-TfOH in MeCN at —35 °C also showed a similar hierarchy of the a-sialyla-tion efficiency between these donors A-Troc sialoside 119 was obtained in 91% (a/)3 = 89/11), A-TFAc sialoside 107 in 92% (aip = 92IS), and AA -diacetyl sialoside 134 in 65% yield (a/p = 62/38), respectively. On the basis of these results, it can be concluded that the efficiency of a-sialylation with a AA -diacetyl sialyl donor is less constant than the corresponding A-Troc and A-TFAc derivatives, depending on the reaction system. 

Several non-natural a2,6-linked sialosides 36-40 with azide or alkyne-modified sialic acid residues were also prepared in excellent yields (86%-93%) from their C2- or C6- modified ManNAc or mannose bearing corresponding azide or alkyne functional groups 30-34 using the one-pot three-enzyme approach and GaipOMe (35) as an acceptor for Pd2,6ST (Scheme 5). 

Scheme 5. One-pot three-enzyme chemoenzymatic synthesis of a2,6-linked sialosides containing non-natural substitutents using GaljSOMe as an acceptor.

The Trypanosoma cruzi trani-sialidase catalyzes the reversible transfer of NeuAc from a NeuAc-a-2,3-Gal-)8-OR sequence to an acceptor hearing the Gal-)8-OR motif (Scheme 42) [54], The enzyme is a particularly useful sialidase because it has very little hydrolytic activity and tends to almost exclusively catalyze transsialylation to a galactose. However a major drawback to this method is that to drive the gly-cosylation to completion, there is a need for large quantities of complex a-2,3-linked sialyl donors, which are generally difficult to obtain from natural sources. Other natural donors with a-2,6- or a-2,8-linked sialic acids have been examined but were discovered to be poor sialyl donors for a-2,3-sialylations catalyzed by T. cruzi trans-sialidase [55]. Simple aryl a-sialosides, such as the 4-nitrophenyl glycoside 122 and methylumbelliferone glycoside 130 (Scheme 43), have been found to be excellent... 

Figure 22 Biosynthesis of sialosides. Sialic acid aldolases catalyze the aldol condensation of W-substituted mannosamines with pyruvate to produce sialic acids. CMP-sialic acid synthetases produce CMP-sialic acid from CTP and sialic acid. Sialic acid is transferred to acceptor molecules by sialyltransferases.

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