Mannosyl bromide

Mannosides are difficult to obtain since here a 2-O-acyl group blocks the -position. 2-O-Benzyl-a-mannosyl bromides give, however, high yields of pure -glycosides with a heterogeneous silver silicate catalyst preventing anomerization and SnI reaction of the bromide H. Paulsen, 1981 B, Q. 

Methyl a-D-mannopyranoside was treated in succession with p-toluene-sulfonyl chloride, carbonyl chloride, and benzoyl chloride, and, without isolating the intermediates, there was obtained in 37% yield methyl 4-0-l enzoyl-2,3-O-carbony 1-6-0-(p-tolylsulfonyl ) -D-mannoside. The tos-yloxyl group of the latter was replaced by iodine, and hydrogenation of the 6-iodo derivative in the presence of a nickel boride catalyst gave methyl 4-0-benzoyl-2,3-0-carbonyl-6-deoxy- -D-mannoside. Treatment of the latter with hydrogen bromide in acetic acid gave crystalline 4-0-benzoyl-2,3-0-carbonyl-6-deoxy-a-D-mannosyl bromide (8) (16). The... 

On the other hand, the synthesis of p-mannosides continues to be a major obstacle. The most commonly used procedure involves mannosyl bromides as donors and insoluble silver salts as promoters [3j. However, the coupling often gives appreciable amounts of the undesired a-anomer. Recent approaches to p-mannosides are based on participation from the 2-position [4], and the desired p-anomers can thereby be obtained exclusively. However, these procedures often require multiple steps for preparation of the key interme-diate(s). 

Following this work, Reichstein and coworkers15 effected the first partial synthesis of a naturally occurring cardenolide, convallatoxin. Convalla-toxin [3/3-0-(6-deoxy-a-n-mannopyranosyl) strophanthidin (9)] is considered to be the most potent of all the known, naturally occurring cardenolides, and is obtained from the blossoms of the lily-of-the-valley (Convallaria majalis). The coupling of strophanthidin (2) with 2,3,4-tri-0- acetyl-6-deoxy-a- L-mannosyl bromide was performed using silver car-... 

In Reichstein s synthesis15 of convallatoxin (9), 2,3,4-tri-0-acetyl-6-deoxy-a-L-mannosyl bromide (13) (a 1,2-trans halide) was employed. In contrast to the preparation of simple glycosides, the use of silver carbonate did not lead to orthoester formation instead, glycoside formation took... 

Because of the expensive nature of the bromide (30), pilot experiments were carried out by using the known" 2,3,4,6-tetrarO-acetyl-a-D-mannosyl bromide (31) in order to establish optimum conditions for the coupling of (30) with (2). Coupling of the acetylated D-mannosyl bromide (31) with strophanthidin (2) was performed in 1,2-dichloroethane with exclusion of light, using freshly prepared silver carbonate. The water was removed azeotropically in the usual manner, and the reaction products... 

This method has been applied also to mannosyl bromide and galactosyl bromide.4 Because alkoxyalkyl radicals are nucleophilic radicals, only alkenes with electron-withdrawing substituents can be usedJ The 1,5-anhydroglycitol side product 11 Is formed in amounts that increase with the decreasing reactivity of alkene 4. 

Composition of Products from Reaction of Tetra-O-acetyl-a-D-mannosyl Bromide with Methanol in the Presence of Silver Carbonate10... 

The compound of Micheel and Micheel was obtained in small amount after treatment of 2,3,4,6-tetra-O-acetyl-a-D-mannosyl bromide with tri-methylamine the bulk of the material remained unchanged. The product apparently resulted from hydrolysis by moisture from the air. The composition was established by analyses, but the identification was reported with a question mark. A 2,3,4,6-tetra-O-acetyl-D-mannose with different physical constants (m.p. 93°, [c ]d +26.3°) was obtained by Levene and Tipson63b by the deliberate addition of water and silver carbonate to tetra-O-acetyl-D-mannopyranosyl bromide its structure was confirmed by conversion to the known pentaacetates. If Micheel and Micheel were correct in their identification, the two acetates could be anomers. The acetylation and deacetylation reactions performed by Maurer and Bohme are additional evidence in favor of this relationship. 

The discussion so far has been concerned primarily with the mechanism of solvolysis of the cis halides. There is no reason to suppose that the trans halides react by a different mechanism, and indeed, tetra-O-acetyl-a-n-mannosyl bromide has been shown to undergo unimolecular solvolysis. On the basis of an SnI mechanism as promoted by the lactol ring oxygen, and of the steric influence of all the groups in the molecule, it should be possible to interpret the reactions of both the cis and the trans halides and to explain the nature of the products from each. 

A different approach to control the stereoselectivity of glycosylations is through the use of heterogeneous catalysis. Catalysts such as silver silicate were developed for this purpose [46]. Reactions of glycosyl halides on the surface of silver silicate are thought to proceed by a concerted mechanism providing, for example, (3-D-mannopyranosides 44 from a-D-mannosyl bromide 43 (Scheme 4.7). 

The effect of the electron-withdrawing acyl group on the stereoselectivity seems to be position-dependent. Systematic studies by van Boeckel and coworkers revealed an interesting effect of the acyl group in the variously protected mannosyl bromide 19 [32] (O Scheme 10). Compared... 

The most successful insoluble silver promoters used thus far in this context have been silver silicate43 and silver zeolite.44 Other insoluble promoters described, earlier starting from a-mannosyl bromides carrying non-participating substituents at 0-2 are silver oxide,45-47 silver oxide and silver perchlorate,48 silver salicylate 49 and silver carbonate.50 The point of using an insoluble promoter together with an... 

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