Mannose 1,2-orthoesters

Self-Condensation of Mannose 1,2-Orthoesters Ready Access to (1 2)-Linked Mannose Oligosaccharides... 

Compound 147 was prepared by mannose 1,2-orthoester 146 using terr-butyl-diphenylsilyl chloride and imidazole in DMF or, better, pyridinium triflate in pyridine. 0-Acetylation or 0-benzylation of 147 gave orthoesters 148a,b. 

In continuation of their studies of the resolution of myo-inositol derivatives via their orthoesters with sugar derivatives, Evstigneeva et al. [296] converted the racemic 1,2 3,4-di-O-cyclohexylidene-wyo-inositol (431) by transesterification with the mannose orthoester (425) into a mixture of diastereoisomers (426) formed by esterification of the 5- and 6-positions of (431). One of the four possible isomers was separated by crystallisation and the other three were obtained by preparative TLC. Partial hydrolysis of the resolved isomers gave both enantiomers of 1,2-0-cyclohexylidene-myo-inositol (432). 

Shvets and co-workers (298) have also prepared chiral 1-O-benzyl-myo-inositols by benzylation of the mannose orthoesters (427) and (428) with subsequent acidic hydrolysis. They were also prepared by partial benzylation of chiral l,2 5,6-di-<9-and 2,3 4,5-di-<9-cyclohexylidene-/ny< -inositols. These chiral monobenzyl ethers are potential intermediates for the synthesis of chiral inositol pentakisphosphates. Reaction of the orthoester (427) [299] with benzoyl chloride or diphenylphospho-chloridate in pyridine at 20 °C gave little reaction, whereas at 80 °C the orthoester group was replaced and both hydroxyl groups of the inositol derivative were acylated (or phosphorylated). 

The synthesis of myo-inositol 1,4,5-triphosphate has been achieved from myoinositol derivatives by formation of D-mannose orthoester derivatives. 

Solvent percv- ture, °C. O-Acetyl-mannose, % O-Acetyl orthoester, % O-Acetyl-0-manno-side, % O-Acetyl-a-manno-side, %... 

The first observation of the instability of carbohydrate orthoesters toward alkali came from Haworth, Hirst and Miller in connection with their experiments on the simultaneous deacetylation and methylation of L-rhamnose methyl 1,2-orthoacetate. These authors noticed that methylation by methyl iodide and silver oxide in the presence of solid sodium hydroxide resulted in the formation of crystalline methyl tri-methyl-/3-L-rhamnopyranoside. A similar result was obtained by Bott, Haworth and Hirst on the simultaneous deacetylation and methylation of triacetyl-D-mannose methyl 1,2-orthoacetate by the use of excessive quantities of dimethyl sulfate and alkali. The reaction produced a mixture of a. and /3 forms of methyl tetramethyl-D-mannopyranoside but the yield was only 40%. When the acetylated orthoester was submitted to methylation with silver oxide and methyl iodide in the presence of sodium hydroxide, the product was mainly trimethyl-rhamnose methyl 1,2-orthoacetate. This result indicates that for the alkaline hydrolysis of orthoesters, hydroxyl ions are necessary. Such ions are present in the dimethyl sulfate-alkali process, but are absent in the methyl iodide treatment except when the reaction mixture contains a little water either by accident or from the decomposition of the sugar molecule. Haworth, Hirst and Samuels examined the behavior of dimethyl-L-rhamnose methyl 1,2-orthoacetate in alkaline solution. When the substance was heated under various conditions with 0.1 A alkali at 70 there was no appreciable hydrolysis at the end of ninety minutes, whereas at 80 for... 

Figure 3.35 Reactions of acylated glycosyl halides under solvolysis conditions. The two canonical forms for the dioxanyl cation are drawn only with mannose and only the predominant exo forms of the orthoester products are shown.

A long series of papers by Shvets and co-workers is devoted to synthesis of asymmetrically substituted myo-inositols and, in particular, inositolphos-phatides. Their route to optically active compounds from wyo-inositol consists of the formation of diastereoisomeric orthoesters in the reaction of a suitably protected racemic myo-inositol derivative with the orthoacetate of D-mannose, followed by the separation of the diastereoisomers and hydrolysis. Naturally occurring ( + ) and (-) bomesitols (3- and 1-0-methyl-sn-myo-inositols) were obtained in this way, among many other enantiomerically pure chiral myo-inositol derivatives. ... 

Regioselective debenzoylation of nucleoside 2, 3 5-tri-O-benzoates using hydrazine hydrate has been reported. With 1 mol reagent in acetic acid-pyridine the 3 5-di-O-benzoyl derivative was produced when the bases were adenine, guanine, or indole, whereas with excess hydrazine hydrate in 1 1 chloroform-methanol, 98% of the 5-O-benzoyl derivative was produced (base = adenine or uracil). 3, 5-Di-O-benzoyl-2-deoxy-nucleosides gave a 90% yield of a 1 1 mixture of 3 - and 5-O-benzoyl nucleosides with 1 mol hydrazine hydrate in pyridine. Treatment of the mannose orthoacetate (5) with benzoyl chloride in pyridine gave 2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl chloride and ethylbenzoate, whereas the related orthoester of mu co-inositol (6) gave 66% of the correspond-... 

D-mannose compounds have been prepared including the orthoester (4)... 

A synthesis of the pseudotrisaccharide destomycin C has been described, using mannose and deoxystreptamine to form a pseudodisaccharide which was then coupled to destonic acid to form the orthoester linkage inversion at the mannose C-4 centre gave the antibiotic. 

The first representative of the orthoester type was prepared by Fischer, Bergmann, and Rabe (19), who, by reacting tri-O-acetyl-a-L-rhamnosyl bromide with methyl alcohol in the presence of silver carbonate, obtained a compound with the same analysis as an acetylated methyl L-rhamnoside but which exhibited the unique property of having one acetyl group resistant to alkaline hydrolysis. A similar derivative of D-mannose was then reported by Dale (20). 

The glycosidic hydroxyl undergoes preferential alkylation when the sugar is alkylated with one equivalent of dimethyl sulfate and alkali 49,4 0 ). The procedure is particularly valuable for obtaining methyl glycosides of the D-mannose type for which the Koenigs-Knorr reaction fails because of orthoester formation. Alkylation of tetra-0-acetyl-/3-D-fructopyranose with silver oxide and methyl iodide leads to the methyl /8-D-fructopyranoside tetraacetate 50). 

Linear Homotrisaccharides. - The nephritogenoside trisaccharide unit a-D-Glc-(1- 6)-P-d-G1c-(1- 6)-a-D-Glc has been prepared by application of the glycosyl sulfoxide procedure. Cellotriose can be made from cellobiose by use of a sesame seed transferase which also transfers from other disaccharide substrates. Treatment of highly concentrated aqueous solutions of D-mannose with an a-mannosidase from Aspergillus niger has resulted in the isolation of the trimers a-D-Man-(l- 2)-a-D-Man-(l->6)-D-Man and a-D-Man-(l 2)-a-D-Man-(1 ->2)-D-Man, and this latter trisaccharide has been formally synthesized by Fraser-Reid and colleagues in studies of the mannan components of phosphatidylinositol membrane anchors. In the course of the work they used the orthoesters 4 as versatile synthetic intermediates. ... 

Exposure to mercury(II) bromide and 2,4collidine converted acetylated gly-cosyl halides to 1,2-orthoesters. Formation of orthoesters under kinetic control (ketene dimethylacetal, pTsOH, DMF) gave 4,6-derivatives 64-66 from d-glucose, D-mannose and methyl a-D-glucopyranoside, respectively, and product 67 from methyl 4,6-0-isopropylidene-a-D-mannopyranoside. Mild acid hydrolysis of 67 gave specifically the 2-0-acetate. This method has been applied to the selective acetylation of monoisopropylidenated furanoses an example is given in Scheme 3. ... 

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