Glycosylation reactions timing

Several other studies concerning tetrazole-containing compounds were leptorted. The 1-bromo-glycosyl cyanide 15 was converted to the tetrazole derivative 16 in 72% yield by treatment with 2 eq LiNs/DMF/S d <96T9121>. Shorter reaction times led to formation of the 1-azido-pyranosyl cyanide. (Hydroxyphenyl) carbenes could be formed by thermal decomposition of the appropriate 5-substituted tetrazoles 17 <96JOC4462>. 

This improvement allowed achieving the synthesis of 2-deoxy disaccharide 103 with high stereoselectivity and good yield in short reaction times. The composition of the reaction mixture was found to be practically independent of the configuration of the S-(2-deoxy-D-glucopyranosyl)phosphorothioate. These results seem to provide an evidence that this glycosylation procedure proceeds via the SN1 displacement reaction mechanism. 

Furthermore some O- and. S -glycosylated pyropheophorbide-a derivatives have been prepared.75 The O-glycosylated pyropheophorbide derivative 97 was obtained by carbohydrate per-acetate glycosylation acid catalyzed method of derivative 96 (Fig. 10). The reagent proportions and the reaction times have been shown to rule the reaction yield. The best results were found when the reagents ratio was 2 1 2 (glycoside pyropheophorbide Lewis acid). Under these conditions the reaction yield was 36% with 83% of anomeric purity. The glycosylated derivatives 97 are diastereomeric mixtures. 

All the described solid-phase glycosylation protocols required long reaction times to proceed in reasonable yields because of the slower reaction kinetics on support than in solution. Furthermore, since no analytical means were available to monitor the progress of the reaction on the bead, development of optimal reaction conditions was difficult. The approach described by Guthrie and coworkers in the early 1970s for... 

Two repeated exposures of resin 38 to the catalyst (9% mol) for 18 h in dichloromethane at room temperature afforded the expected allyl lactoside in an encouraging isolated yield of 81% from resin 35 (90% per step). Traces of dimerized compounds resulting from cross-metathesis were detected as the only side products. Extension of the oligosaccharide chain was subsequently performed first by deacetylation (excess NaOMe in 4/1 CH2Cl2/MeOH at r.t.) and glycosylation with known lactosyl donor 40 in conditions similar to those mentioned above. Cleavage was performed twice as described above, but with a reduced reaction time of 6 h in this case tetrasaccharide 42 was isolated in 51% yield from 35 (84% per step). No dimerized products were detected. 

The standard conversion of alcohols into their xanthate esters through reaction with carbon disulphide and an alkylating agent is improved by the addition of a quaternary ammonium salt [69]. Excellent yields (>90%) are obtained in relatively short reaction times under mild conditions. The formation over relatively short reaction times of O-glycosyl xanthates from partly protected glycosides has been described using a stoichiometric amount of the quaternary ammonium salt [70]. 

It is therefore recommended that the glycosyl halide should be added slowly to a solution of the alcohol in order to maintain as high a concentration of the latter as possible. Further, it was suggested that for maximum efficiency the activity of the silver salt should be ascertained before use by polarimetric means so that optimal reaction times can be employed. The beneficial effects of iodine which is often used in the reaction are suggested to result from the specific inhibition of the side reactions. Rather surprisingly, however, the Koenigs-Knorr condensation was found to occur more slowly in the presence of iodine than in its absence, so the effect would not appear to be direct. 

The utilization of compound 54 in the aldolization showed higher yield of the product (92%) after 30 min, compared to that (73%) of a trityl catalyzed reaction. The similar results were obtained in the glycosylation reaction 85% (o/p ratio 9 91) and 72% (cx/p ratio 10 90) respectively. The application of the highly hindered tetrakis[pentafluorophenyl]borate anion is remarkably advantageous for the stabilization of the positive charge in the carbocation 54 and at the same time promotion of its accessibility to the interaction with a carbonyl species. 

Some examples of the behavior of unsaturated ketonucleosides under alkaline conditions have also been reported. The enol acetate 61a is more stable than the parent ketonucleoside 36a. In 0.1 M methanolic sodium hydroxide, free theophylline was detected only after 4 h, by which time, loss of the acetyl group was complete a reaction time of more than 18 h was needed for complete cleavage of the glycosylic bond.51 In alcoholic solution, the unsaturated 4 -ketonucleoside 66 was very sensitive to nucleophilic attack, and decomposed rapidly, with elimination of the nitrogenous base.31 Thus, treatment with sodium borohydride at — 70° led to complete decomposition within 10 min but, when sodium borohydride was added to a solution of 66 in 1,2-dichloroethane containing acetic acid, fast reduction occurred, and no degradation was observed.31... 

Although the anomeric configuration of the glycosyl phosphate in natural lipid A had not been elucidated at that time, it was assumed to be a and we employed a sufficient long reaction time for this phosphorylation to secure formation of a-phosphates in the following synthesis. Meanwhile the natural glycosyl configuration was established to be a (6) and our choice is fortunately correct. 

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