L-Rhamnose methyl 1,2-orthoacetate

Similar results were obtained with 3,4-dimethyl-L-rhamnose methyl 1,2-orthoacetate. Hydrolysis of the glycosidic group took place so quickly in acid solution that the first stage of the reaction could not be followed polarimetrically. The rotation of the substance in pure water, +36°, changed wuthin one minute after addition of the acid... 

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... 

Carbohydrate orthoesters, first reviewed by Pacsu more than 60 years ago [8], were reported by Fischer et al. [9] as by-products of the Koenigs-Knorr reaction [3] of acetobromo-L-rhamnose (1) with methanol. Orthoacetate 3 was isolated along with the expected a- and P-methyl rhamnosides 2 (Scheme 5.2). However, its true structure was assigned only 10 years later by several research groups [10-12]. 

These conclusions do not comply with the explanation given by Haworth, Hirst and Samuels and by Pacsu for the reaction mechanism of the acid-catalyzed hydrolysis of the rhamnose and turanose orthoesters, respectively. It seems, however, that the experimental data of these authors can be re-interpreted without difficulty, to fit into the picture given for the reaction mechanism of the maltose orthoester. The first and very rapid reaction, which Haworth and coworkers associated with the removal of a methoxyl residue, would, as in the maltose orthoester, involve the rupture of the bond between the central carbon atom and that oxygen atom which is linked to carbon atom 1. This process liberates the 3-form of L-rhamnose substituted at position 2 by a methyl hydrogen orthoacetate residue. However, since this intermediate is... 

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