P-Disaccharides

The evidence thus far indicates the PBP1 set as functioning in cylindrical cell wall synthesis. PBP 1A has the higher affinity for (3-lactam compounds. Inhibition of PBP 1A function alone by these antibiotics is not necessarily lethal to the cell, however. It is imperative that both PBPs be inhibited to effect cell lysis. The two enzymes catalyze transglycosylation and transpeptidation utilizing the bactoprene-P-P-disaccharide-pentapeptide (see Fig. 6-4). 

Coupling of the ketone glycosyl donor 90 and acceptor 91 was conducted by addition of Tf20 to the mixture of 90, 91, and DTBMP to provide a mixture of a-disaccharide 94 and its anomeric p-disaccharide (4 1) in 74% yield (Scheme 5). Glycosylation of acceptor 93 with glycosyl donor 92, on the other hand, carried out under the different reaction condition for the synthesis of P-mannoside 96. Thus, the donor 92 was first activated by the addition of Tf20 and then reacted with the acceptor 93 to afford exclusively the P-disaccharide 96 in... 

This methodology was further enhanced by the realisation that an acyl protecting group at the C-2 position effectively hinders the formation of a carbonium ion intermediate [31]. This phenomenon was exploited by Paulsen and co-workers in the coupling of mannoside donor 11 with the GlcNAc precursor acceptor 12 by activation with silver silicate, to afford the P-disaccharide 13 in a 65% yield (Method 1) [32]. 

The first experiments with iodides revealed that better alkylating agents are required. Excellent reactivity was found for triflates providing, for instance with 2,3-0-isopropylidene-D-ribose and derivatives, Spending on the reaction conditions, very high yields of a- and p-disaccharides respectively. ... 

The coupling reaction is stereoselective for formation of the p-disaccharide. Removal of the ester protecting groups and hydrolysis of the methyl glycoside are required to complete... 

In the nomenclature of oligosaccharides, trivial names are still used for a number of substances (e.g. maltose, cellobiose or trehalose. Figure 4.5). In the case of reducing disaccharides, systematic nomenclature takes as its basis the name of the monosaccharide with a free hemiacetal hydroxyl group, which is preceded by the name of the substituted monosaccharide and the respective anomeric configuration is indicated (a- or P-). Disaccharide maltose (Figure 4.5), formed by condensation of... 

Scheme 13. Synthesis of a 2 -deoxy-P-disaccharide with a glycal epoxide as glycosyl donor.

Scheme 18. Stereoselective syntheses of 2 -deoxy 2 -phenylseleno-a- and P-disaccharides.

When the donor is correctly adjusted to the acceptor, yields are high (64-97%). However, acidic conditions of the glycosylation reaction may induce partial anomerization at the reducing end of the obtained disaccharide. In that case, more reactive A -phthaloylglucosamine donors can be used a sequential treatment converts then the A -phthaloyl group into the required Af-formyl substituent. Radical deamination at C-2 through an isonitrile delivered 2 -deoxy-P-disaccharides 132 in 65 89% overall yields (Scheme 29). 

Insoluble silver salts such as silver silicate favor direct Sn displacement of an anomeric bromide by alcohols [88]. When applied to 2-deoxy-pyranosyl bromides, this procedure can lead to 2 -deoxy-P-disaccharides with a good stereoselectivity. For instance (Scheme 32), bromide 141, where an ester group at 0-4 can also favor [85] P-glycoside formation, reacted with the sugar alcohol 142 in the presence of silver silicate to give the disaccharide 143 in 85% yield (P a 5.4 1) [89]. 

Anomeric a,P-S -phosphorodithioates can also be obtained [99] from glycal epoxide 58. After pivaloylation at 0-2, they can be activated by methyl triflate to give with sugar alcohols exclusively P-disaccharides in good yields Selective deoxyge-... 

---