Mannosyl-phosphate

Leloir110(a) has described a conversion of D-mannosyl phosphate to D-mannose 6-phosphate by phosphoglucomutase, and here, too, the reaction requires catalytic quantities of a-D-glucose 1,6-diphosphate. The role of the latter is probably to generate a-D-mannose 1,6-diphosphate as follows. 

Although addition of activated phosphoramidite to hemiacetals of manno-pyranoses under thermodynamic control has been reported to deliver exclusively a-phosphates in some cases,43 anomeric mixtures with preponderance of a-anomer have been reported in other examples.10,44 Since formation of phosphorotetrazolidite is a rate-limiting step of the process, initial activation of phosphoramidite followed by addition of nucleophilic hemiacetal should accelerate condensation and favour the formation of the thermodynamic a-product. Indeed, reaction of hemiacetal 101 with dibenzyl phosphorotetrazolidite assured exclusive a-selectivity of the resulting glycosyl phosphate 102.43 The accumulation in the reaction mixture of mildly acidic 1H-tetrazole, which is liberated upon reaction of tetrazolidite with hydroxylic component, could also favour predominant formation of the a-phosphate (Scheme 18, A). Conventional hydrogenolysis afforded the a-mannosyl phosphate 103. 

In addition to the coupled-signal method just described, phosphorylated carbon signals can be detected by use of praseodymium chloride, which displaces a- and /8-carbon resonances of a,/8-D-mannose 6-phosphate and a-D-mannosyl phosphate downfield, with little effect on other resonances. Europium chloride has analogous properties, except that the displacements are upfield. With certain polysaccharides, such as the O-phosphonomannan of Hansenula capsulata (29), the sig-... 

Scheme 6.8 Formation of a-mannosides on cyclic mannosyl phosphate activation.

This enzyme [EC 2.4.1.83] which catalyzes the following reaction GDP-mannose + dolichyl phosphate to yield GDP -h dolichyl D-mannosyl phosphate. 

In the first Section, the dolichol pathway of protein glycosylation is introduced, and the reader is made familiar with the various reactions in the formation of the lipid and carbohydrate moieties of lipid-linked saccharides. Three different classes of compound are known so far (a) isoprenoid alcohol esters of monosaccharide monophosphates, such as D-mannosyl and D-glucosyl (dolichol phosphate), (b) such isoprenoid alcohol esters of saccharide diphosphates as dolichol diphosphate linked to 2-acetamido-2-deoxy-D-glucose and to oligosaccharides, and (c) retinol (D-mannosyl phosphate). The dolichol-linked sugars occur in all eukaryotes. 

The conversion of D-mannose 6-phosphate into D-mannosyl phosphate is catalyzed by phosphomannomutase, an enzyme distinct from phosphoglucomutase. Both enzymes have been detected by Mathe-son705 in cassia seeds, mung beans, orchid tubers, and pea seedlings. These enzymes from cassia seeds have been separated from one another by chromatography on DEAE- and O-phosphono-cellulose columns, and further characterized. Phosphomannomutase from animal sources requires the presence of either D-galactose 1,6-bisphosphate or D-mannose 1,6-bisphosphate for activity.708 D-Mannosyl phosphate may then be enzymically transformed into GDP-D-mannose in the... 

The action of /3-D-mannosidase finally degrades the D-manno-oligo-saccharides, to afford free D-mannose molecules details of this process were given in an earlier article.12 An enzyme identified as oligo-/J-D-mannosyl-(l- 4)-phosphorylase719 may also take part in the mobilization of D-galactomannan in seeds. This enzyme, in the presence of orthophosphate, acts on D-manno-oligosaccharides (obtained from partial hydrolysis of D-mannan), and yields /3-D-mannosyl phosphate. 

The aromatic phenol was varied to explore the scope of the O-to-C conversion with mannosyl phosphates. Using phosphate 9, the a-C-mannosides of 2-naphthol and 3-benzyloxy phenol (23 and 25, Table 1) were synthesized in excellent yield. O-Mannosides were obtained exclusively with less nucleophilic aromatic systems, such as 3-acetoxy phenol. Several non-phenolic aromatic systems were unsuccessful in the formation of C-aryl or O-aryl glycosides. Reaction of 9 with furan, thiophene, trimethoxybenzene, and indole in the presence of TMSOTf did not result in any product formation. Interestingly, activation of 9 in the absence of any aromatic nucleophiles gave 26 as the major product via an intramolecular C-glycosylation (Figure 1) (79). 

C-Alkyl glycosides are useful carbohydrate mimetics, commonly employed as enzyme inhibitors. The formation of various C-alkyl glycosides was evaluated with phosphates 9 and 12 (Table 3). Mannosyl phosphate 9 was activated with TMSOTf and coupled to allyltrimethylsilane to provide a-allyl glycoside 2 (18) in excellent yield (93%). Coupling of 9 to the cyclopentanone derived trimethylsilyl enol ether 35 afforded 34 as a mixture of diastereomers in 84%... 

Hashimoto and coworkers successfully applied their phosphite method to selective -manno-sylation [63,64,65] (O Scheme 21), Similar to the case of Crich s mannosylation, cyclic protection at the 4- and 6-positions is essential. Mannosyl phosphate and phosphoramidate were also investigated [65,66]. Toshima et al. used the glycosyl phosphites activated with a solid acid catalyst to give -mannoside predominantly [67,68]. 

Preliminary to a second-generation synthesis of the 3-(9-methyl-y-( 1 -4)-mannans, Kishi and co-workers screened a series of mannosyl phosphates for the influence of the 0-2 protecting group and the anomeric stereochemistry of the donor on the outcome of the glycosylation reaction. As may be seen from Scheme 26, the use of benzyl ether protection under these homogeneous solution-phase conditions gave selectivities that were insufficient, whereas the 2-benzoates gave exquisite a-selectivity.34... 

Scher and coworkers showed that an alkali-stable, acid-labile lipoid material was synthesized from GDP-D-mannose and an endogenous lipid in crude, cell-free preparations of Micrococcus lysodeik-ticus. This compound has been shown to be a polyisoprenyl (d-mannosyl phosphate) it can serve as a D-mannosyl donor in the enzymic synthesis of a homopolysaccharide of D-mannose. The poly-isoprenol was found to be a C55 compound containing two internal, trans double bonds. It was shown that only the D-mannosyl group of GDP-d -mannose is transferred to the polyisoprenyl phosphate ( undecaprenyl 1-phosphate ), and that the reaction is readily reversible. 

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