Glycosyl phosphates automation

The coupling protocols described in the two previous examples can be combined to allow for the synthesis of branched carbohydrates.19 The automated solid-phase synthesis of a tetrasaccharide is illustrated in Scheme 4. Both glycosyl phosphate and glycosyl imidate building blocks were used along with acetate and levulinate esters as temporary protecting groups. 

TABLE II Automated Coupling Cycle Used with Glycosyl Phosphates 1 ... 

Scheme 3. Automated carbohydrate synthesis using glycosyl phosphates.

Automated Synthesis of /J-Glucans Using Glycosyl Phosphates. 47... 

Given our success with the use of trichloroacetmidate donors, we sought to explore the use of glycosyl phosphates in an automated protocol.1... 

The phytoalexin elicitor (PE) family of /1-D-glucans (Fig. 5) was selected as a target because these oligosaccharides had been synthesized previously in solution48,49 and on the solid support.50,51 It was our intention to investigate not only the application of glycosyl phosphates to automated solid-phase synthesis, but also to compare our method to the previously described reports of PE syntheses. 

After developing procedures for the activation and coupling of anomeric trichloroacetimidate and glycosyl phosphate donors as well as for the deprotection of acetyl and levulinoyl esters, we designed a synthesis utilizing all aspects of our automated chemistry. Trisaccharide 24, composed of three... 

Melean, L G, Love, K R, Seeberger, P H, Toward the automated solid-phase synthesis of oligoglucosamines systematic evaluation of glycosyl phosphate and glycosyl trichloroacetimidate building blocks, Carbohydr. Res., 337, 1893-1916, 2002. 

Glycosyl phosphates, building blocks in automated solid-phase synthesis of complex oligosaccharides, were prepared via a 1,2-epoxide (O Scheme 13). Oxidation of the appropriately substituted D-glucal 28 with DMDO followed by reaction with dialkyl phosphate provided the -phosphate 33, which anomerized further to the a-analog [31]. 

Scheme 11.2-2 Automated oligosaccharide synthesis with glycosyl phosphates. Initial glycosylation of resin-bound acceptor produces a coupling product that may be subsequently deprotected. Iteration of coupling and deprotection cycles with phosphate donors 4-8 followed by cleavage of the resin-bound oligosaccharides and purification gives 1-3.

This chapter desribes the synthesis of glycosyl phosphates and their use as glycosylating agents. Their use in die construction of complex oligosaccharides, both in solution and on solid support, is presented. Their ease of synthesis in combination with their rapid activation have made them ideal glycosylating agents to be used for automated solid phase oligosaccharide synthesis. 

Figure 4. Automated solid-phase synthesis using glycosyl trichioroacetimidates and glycosyl phosphates.

Soybean plants can produce the antibiotic phytoalexin when exposed to a fungal /1-glucan. A phytoalexin elicitor hexasaccharide was synthesized by automation using glycosyl phosphate building blocks (Scheme 7). The functionalized resin was submitted to building blocks in a five-fold excess with stoichiometric amounts of trimethylsilyl trifluoromethanesulfonate for 15 minutes at - 15 °C. The resin was washed and treated with hydrazine to affect the deprotection of the C6 hydroxyl. The sequence was repeated three times,... 

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