Disaccharide Formation

G. Posner and D. S. Bull, Molecular sieves promote stereocontrolled a,a-disaccharide formation via direct dimerization of free sugars, Tetrahedron Lett., 37 (1996) 6279-6282. 

Figure 10. Methodfor the introduction ofa variety of fatty acyl residues after disaccharide formation.

An original way to increase the yield of disaccharides by condensation of monosaccharides has been introduced [10]. The solution of substrates is circulated through columns of immobilized enzyme and activated carbon connected in series. The procedure is based on the preferred adsorption, by activated carbon, of di- over monosaccharides. By eliminating the products from the system, the equilibrium is continually shifted toward disaccharide formation. This method has also been applied to trisaccharide syntheses [11]. 

Thioglycosides are activated for disaccharide formation" by means of an NBS-triflate salt combination. 

Glycosylation by trityl sugars. Disaccharide formation catalyzed by AgC104-SnCl4 makes it possible to use the more stable trityl sugars (in situ detritylation) as nucleophiles. 

Table III. Yield of Glycosidase-catalyzed Disaccharide Formation at Various Substrate Concentrations...

These reactions can be rationalized by envisaging a glycosyl cation intermediate that is subject to competitive interception either by the hydroxyl group of another sugar, leading to disaccharide formation, or by water, leading to overall hydrolysis (Figure 5.2). 

Scheme 10.6 (a) Disaccharide formation by glycosylation reaction of protected mannoside (glycosyl donor) and galactoside (acceptor), (b) Glycosylation reaction involving mannosyl donor and acceptor to form dissacharide. Orthoester was also formed. 

After disaccharide formation, the lipid A 4 kinase, catalyzes the transfer of the y-phosphate from ATP to the 4 position of DS-l-P to form tetraacyldisaccharide l,4 -ftw-phosphate (also known as lipid IVa) (Figure 2) [34], Incorporation of the 4 phosphate is required for subsequent reactions in lipid A biosynthesis [35], Also, lipid A-like molecules are maximally active as activators of signal transduction in mammalian cells when both the 1 and 4 phosphates are present [13, 36, 37],... 

Disaccharide Formation. Treatment of glycoside (3) with 2,2 -dipyridyl disulfide and Tri-n-butylphosphine in CH2CI2 rapidly yields thiopyridyl derivative (4) as a mixture of anomers. Activation of (4) with iodomethane, followed by treatment with glycoside acceptor (5), affords the disaccharide fragment of aver-mectin (6), exclusively a-linked in 78% yield (eq 4). Although other methods are available, this protocol offers advantages in practicality and stereoselectivity. 

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