Reactions at Oxygen Atoms
2.1
167
3.4 Silylation
Anomeric silyl ethers have been prepared from 1-OH sugars and the corresponding silyl chloride in the presence of a base. When the hydroxyl group at C-2 is unprotected silyl group
migrations away from the anomeric center have been observed [458].
3.5 Phosphorylation and Phosphitylation
Glycosyl phosphates are intermediates in biological glycosyl transfer and are constituents of
cell membranes [459]. Both chemical and enzymic methods are available for the synthesis of
specific phosphates. In the preparation of certain glycosyl phosphates, enzymic synthesis with
the appropriate phosphorylase provides the simplest preparation. In this fashion, α-D-glucopyranosyl phosphate is readily prepared by the phosphorolysis of starch or glycogen [460].
Chemically, synthesis of glucosyl phosphates also may involve two different approaches based
either on activation of the glycosyl oxygen or activation at the anomeric carbon. In the latter,
glycosyl acetates [461], orthoesters [462], glycosyl halides [463], trichloroacetimidates [464],
vinyl glycosides [465], glycals [466], or 1,2-orthoesters [467] are used as glycosyl donors and
they are not the aim of this chapter. The above two-step procedures ensure in most cases the
anomeric purity of the final glycosyl phosphates.
On the other hand, several alternative procedures for the synthesis of glycosyl phosphates
involving 1-OH activation have been developed. The thallium salt of the anomeric hydroxyl
readily undergoes substitution with a phosphochloridate in benzene or acetonitrile
( > Scheme 82) [468]. The configuration of an organo-phosphate moiety introduced at the
anomeric position is strongly influenced by the choice of solvent, so that a preponderance
of either the α- or β-phosphate may be attained. These differences are reminiscent of solvent effects observed in syntheses of O-acyl esters and reflect differences in the anomeric
composition in the reducing sugars as well as in the relative reactivities of the two anomers.
Similarly, α-phosphates of N-acylglucosamine are prepared in high yields via the reaction of
the corresponding 1-O-lithium salts with phosphorochloridate at low temperatures [469].
⊡ Scheme 82
Preparation of aldosyl phosphates
2.1
167
3.4 Silylation
Anomeric silyl ethers have been prepared from 1-OH sugars and the corresponding silyl chloride in the presence of a base. When the hydroxyl group at C-2 is unprotected silyl group
migrations away from the anomeric center have been observed [458].
3.5 Phosphorylation and Phosphitylation
Glycosyl phosphates are intermediates in biological glycosyl transfer and are constituents of
cell membranes [459]. Both chemical and enzymic methods are available for the synthesis of
specific phosphates. In the preparation of certain glycosyl phosphates, enzymic synthesis with
the appropriate phosphorylase provides the simplest preparation. In this fashion, α-D-glucopyranosyl phosphate is readily prepared by the phosphorolysis of starch or glycogen [460].
Chemically, synthesis of glucosyl phosphates also may involve two different approaches based
either on activation of the glycosyl oxygen or activation at the anomeric carbon. In the latter,
glycosyl acetates [461], orthoesters [462], glycosyl halides [463], trichloroacetimidates [464],
vinyl glycosides [465], glycals [466], or 1,2-orthoesters [467] are used as glycosyl donors and
they are not the aim of this chapter. The above two-step procedures ensure in most cases the
anomeric purity of the final glycosyl phosphates.
On the other hand, several alternative procedures for the synthesis of glycosyl phosphates
involving 1-OH activation have been developed. The thallium salt of the anomeric hydroxyl
readily undergoes substitution with a phosphochloridate in benzene or acetonitrile
( > Scheme 82) [468]. The configuration of an organo-phosphate moiety introduced at the
anomeric position is strongly influenced by the choice of solvent, so that a preponderance
of either the α- or β-phosphate may be attained. These differences are reminiscent of solvent effects observed in syntheses of O-acyl esters and reflect differences in the anomeric
composition in the reducing sugars as well as in the relative reactivities of the two anomers.
Similarly, α-phosphates of N-acylglucosamine are prepared in high yields via the reaction of
the corresponding 1-O-lithium salts with phosphorochloridate at low temperatures [469].
⊡ Scheme 82
Preparation of aldosyl phosphates