Sialosyl donors

Novel sialosyl donors, S-benzoxazolyl and S-thiazolyl sialosides, have been synthesized [170], Both SBox and STaz sialosides proved to be excellent glycosyl donors... 

Synthesis of N-5-Derivatives of Neuraminic Acid and Their Application as Sialosyl Donors... 

This review summarizes the latest developments in the chemistry of sialic acid which involve modifications of the natural 5-acetamido function (NHAc) into a) N-acetylacetamido (NAca), b) azido (N3), c) N-trifiuoroacetamido (NHTFA) and d) N-trichloroethoxycarbonyl (NHTroc). Last section is dedicated to protecting groups that have been introduced at the N-position but fiieir potential as sialosyl donors has not emerged yet, e.g. tert-Butoxycarbonyl (Boc), Benzyloxycarbonyl (Z or CBz) and 9-Fluorenylmethoxycarbonyl (Fmoc). 

The synthesis of S-N-azido derivatives of N-acetylneuraminic acid has been accomplished by both enzymatic and chemical methods. In particular, SchmidP and Wong described the introduction of the azido group from known sialosyl donors 11a and 11b respectively by using trifluoromethanesulfonyl azide (triflic azide, TfNs) as the diazo transferring reagent (Scheme 3). 

Recently, phosphite sialosyl donors bearing a C-S trifluroacetamido group were applied to the synthesis of a(2-9) oligomers (Scheme 5). ... 

Based on these results, sialosyl donors bearing N-Troc (37, entry 2), N-TFA (51, entry 8) and N-trichloroacetate (52, entry 9) gave the best yields and stereoselectivity. 

Recently, De Meo reported the application of the SBox approach to stereoselective a-sialylation and to the convergent synthesis of a GM3 analog (74). In the latter synthesis, selective activation of the SBox moiety of the sialosyl donor over the S-ethyl moiety of the galactosyl acceptor was conveniently achieved in the presence of AgOTf The obtained disaccharide was used in subsequent coupling directly to afford the desired GM3 trisaccharide sequence in good overall yield. 

When the above glycosylation reactions were repeated with the active arylthio-oc-sialosyl donors 4 and 5 [23] under the same reaction conditions (CH2CI2, room temperature) the yields were similar and the stereoselectivity was only marginally reduced (entries 3 and 4 in Table 1). The reaction was faster for the more reactive donor 5 compared to 4. Changing the solvent from CH2CI2 to a 1 1 mixture of CH3CN CH2Cl2 had two beneficial effects (nitrUium effect) [38]. The reacticm time... 

Table 1 Sialylation of glycosyl acceptor 8 with sialosyl donors 2-7...

Following the classical syntheses of aromatic a-sialosides by phase transfer catalysis starting with the per-O-acetylated sialosyl chloride methyl ester, further aromatic a-sialosides could be prepared with sesamol (4), 2-chloro -nitrophenol (5), and 4-chloro-5-methyl-4-nitrophenol (6) [36]. In TcTS-sialylations none of these modified donor substrates showed any sialylation of methyl p-lactoside (7) to give the methyl sialyllactoside (8). It may be assumed that both steric and electronic factors affect interactions with aromatic and/or hydrophobic amino acid residues in the enzyme (Scheme 1). 

As previously shown, 3-fluoro sialosyl fluorides could be employed as donor substrates for TcTS. Due to the fluoro substituent and its pronounced electron-withdrawing features at the anomeric center, these derivatives show delayed reactions with acceptor structures [28]. This effect proved to be useful in determination of essential mechanistic aspects, since the intermediate enzyme substrate complex could be crystallized and studied [25, 26]. By further modification via introduction of a 9-benzamide function as in compound 24 this effect was increased. In contrast to the expected outcome the enhanced binding of this aromatic residue was unexpectedly due to its location in the acceptor-binding site rather than in the glycerol sidechain binding domain, as evidenced by X-ray structural studies (Fig. 11) [52]. 

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