Anomeric phosphorylation

Additional problems of anomeric phosphorylation are the control of anomeric selectivity and the increased lability of the products. The preparation of anomeric sugar phosphates can be accomplished via two distinct methods. The first commences with a free anomeric hydroxyl and can be considered as a standard phosphorylation. The second approach... 

Anomeric phosphorylation by glycosylation methods In the above-discussed phosphorylation methods, the sugar hydroxyl acts as the nucleophile and the phosphorylating agent as the electrophile. However, phosphorylation of the anomeric centre may also be performed by another approach where the saccharide contains a leaving group. 

Ferrieres and Plusquellec described the synthesis of per-acetylated S-benzothiazolyl galactofuranosides from P-D-galactofuranose pentaacetate in the presence of BFs-EtaO in 83% yield as an anomeric mixture (52, 55). The obtained thioimidates were then deprotected and applied in anomeric phosphorylation. A number of acylated S-benzothiazolyl and S-(5-methoxy)benzothiazolyl derivatives of D-gluco, D-galacto, and D-ribofurano series have been reported by Khodair et al (34). While the syntheses of hexoses were accomplished from acetobromosugar and the corresponding sodium thiolates in MeCN, the synthesis of thioribofruunoside derivative was accomplished from ribofiiranose tetraacetate and trimethylsilylated thiols in the presence of TMSOTf (34). 

Subsequently, 22a was converted into the per-benzylated glycosyl donor 22b by sequential deacetylation and benzylation under standard conditions in 87 % yield. Glycosylation of acceptor 23 with 22b was performed in the presence of TMSOTf yielding the disaccharide 24 in 80 % yield with complete 1,2-cis stereoselectivity. Ferrieres and Plusquellec described the synthesis of per-acetylated thiopyrimidinyl furanosides and their application to anomeric phosphorylation 32, 33). 

A more complicated reaction sequence has been used by Ukita and Nagasawa (59) in their synthesis of 2-deoxy D-ribose 5-phosphate (2-deoxy D-erythro-pentose 5-(dihydrogen phosphate)), (29). They phosphorylated a mixture of the anomeric methyl deoxyribofuranosides (24)... 

The isomerism existing between the pairs of nucleotides was attributed to the different locations of the phosphoryl residues in the carbohydrate part of the parent nucleoside,49 63 since, for instance, the isomeric adenylic acids are both hydrolyzed by acids to adenine, and by alkalis or kidney phosphatase to adenosine. Neither is identical with adenosine 5-phosphate since they are not deaminated by adenylic-acid deaminase,68 60 and are both more labile to acids than is muscle adenylic acid. An alternative explanation of the isomerism was put forward by Doherty.61 He was able, by a process of transglycosidation, to convert adenylic acids a" and 6 to benzyl D-riboside phosphates which were then hydrogenated to optically inactive ribitol phosphates. He concluded from this that both isomers are 3-phosphates and that the isomerism is due to different configurations at the anomeric position. This evidence is, however, open to the same criticism detailed above in connection with the work of Levene and coworkers. Further work has amply justified the original conclusion regarding the nature of the isomerism, since it has been found that, in all four cases, a and 6 isomers give rise to the same nucleoside on enzymic hydrolysis.62 62 63 It was therefore evident that the isomeric nucleotides are 2- and 3-phosphates, since they are demonstrably different from the known 5-phosphates. The decision as to which of the pair is the 2- and which the 3-phosphate proved to be a difficult one. The problem is complicated by the fact that the a and b" nucleotides are readily interconvertible.64,64... 

The phosphate of ethylene glycol must derive from the ribitol phosphate moiety, which consequently is phosphorylated at a primary position, assumed to be 0-5 of (pro-D)-ribitol for biosynthetic reasons. In the proposed structure for the S10A repeating-unit (14), the anomeric natures of the sugar residues were not determined. The optical rotations of S10A and the hexasaccharide, [a]D +12° and +11°, respectively, indicate that they contain both a- and /3-D-linked sugar residues. 

Accordingly, phosphoric acid mono- and di-esters permit uncatalyzed glycosyl transfer from 0-(glycosyl)trichloroacetimidates (52a,55-57,58a,58b). The reaction is thus very useful in the synthesis of glycophos-pholipids (1,55), which are important constituents of cell membranes (1). Commonly, direct phosphorylation at the anomeric hydroxyl group leads to... 

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. 

Not surprisingly the procedures described in Section 3.7.2 for the phosphorylation of nonanomeric hydroxyl groups, that is, the phospho-triester, phosphite triester, and 77-phosphonate approaches, have been applied to the preparation of anomeric phosphates.103d,e 110... 

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