Synthesis of Disaccharides

In the first step, an a-D-glucopyranosyl residue is transferred from the glycosyl nucleotide donor to D-glucopyranose 6-phosphate, to yield the 6 -phosphate of a, a-trehalose (7). 

Analysis of the enzymically synthesized product by chemical and enzymic methods, as well as by optical rotation, showed that it was identical with the trehalose phosphate isolated from the fermentation products of dry yeast.  

The formation of trehalose 6 -phosphate by the yeast enzyme appears to be irreversible. This must be attributed to some factor other than an unfavorable equilibrium, since reversibility of the reaction could not be demonstrated even when n-glucose 6-phosphate dehydrogenase or uridine 5-(a-D-glucopyranosyl pyrophosphate) dehydrogenase were added in an attempt to drive the reaction in the opposite direction. An upper limit of 4400 cal. was calculated for the —AF° of hydrolysis of the glucosidic bond of a,a-trehalose 6 -phosphate this value is admittedly unreliable. 

In the second step, a,a-trehalose 6 -phosphate is hydrolyzed by a phosphatase to the free disaccharide. The phosphatase from flies has been purified to a high degree and shown to be specific for a,a-trehalose 6 -phosphate.  

It has been shown by Leloir and others that the synthesis of sucrose can occur in extracts from a number of plants by two different reactions. 

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Figure 10.32 Applications of bidirectional chain extension for the synthesis of disaccharide mimetics and of annulated and spirocyclic oligosaccharide mimetics using tandem enzymatic aldol additions, including racemate resolution under thermodynamic control.

Huang, S.S., Yu, H. and Chen, X. (2007) Disaccharides as sialic acid aldolase substrates synthesis of disaccharides containing a sialic acid at the reducing end. Angewandte Chemie-International Edition, 46, 2249-2253. 

M. Wilstermann and G. Magnusson, Synthesis of disaccharide glycosyl donors suitable for introduction of the /i-D-Galp-0 >3)-a- and -jS-D-GalpNAc groups, Carbohydr. Res., 272 (1995) 1-7. 

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

Anomeric alkylation has been extensively studied by Schmidt and co-workers,62 and the main alkylating agents used were dialkyl sulphates, benzyl bromide, allyl bromide63 or various O-triflates, allowing the synthesis of disaccharides.64 The stereochemical outcome of anomeric alkylation is known to depend on many parameters such as the base, the solvent and its effect on solubility and concentration, the temperature, chelation effects, presence of additives, and nature of the electrophilic species.62 65... 

A Michael addition-Nef reaction sequence was used in a synthesis of disaccharides. Addition of the sodium salt of 1-thio-D-glucose to sugar nitroolefin 112 gave a mixture of isomers 113. The subsequent deacetylation, followed by a Nef reaction, afforded the S -disaccharides 114 and 115 (Scheme 35).82... 

Fig. 39 Dipolar cycloaddition methodology in the synthesis of disaccharide derivatives.

Scheme 2.12 Synthesis of disaccharides using a polymer-bound thioethyl glucosyl donor.

It has long been recognized that polymeric supports for oligosaccharide synthesis do not need to be insoluble.33 Wang et al. applied the sulfoxide glycosylation method to the synthesis of disaccharide 79 (Scheme 3.14). The key feature of this work was the base-labile linker. Sulfoxide 74 was used to glycosylate polyethylene glycol... 

Scheme 10.6 General strategy for the liquid-phase synthesis of disaccharides using glycosidases.

The synthesis of disaccharide 61 is reasonably efficient (10 steps from 53,17% overall yield) and is readily amenable to scale up. Nevertheless, in contemplating extensions of this chemistry to the synthesis of differentially protected derivatives of D-olivose (e.g., 63, Figure 18) needed for construction of the olivomycin CDE trisaccharide, it became apparent that this approach is unattractive because the required starting... 

J. C. McAuliffe and O. Hindsgaul, The synthesis of disaccharides terminating in D-septanosyl residues using acyclic intermediates, Synlett (1998) 307-309. 

Scheme 2.2.5.17 Synthesis of disaccharide analogues with variable configuration and tether length from generic dialdehyde precursors by Barbier allylation and tandem a.co-aldolization.

S. J. Danishefsky, Route from glycals to mannose p-glycosides, J. Org. Chem. 59 1892 (1994) G. Stork and G. Kim, Stereocontrolled synthesis of disaccharides via the temporary silicon connection, J. Am. Chem. Soc. 114 1081 (1992) P. J. Garegg, Saccharides of biological importance Challenges and opportunities for otganic synthesis, Acc. Chem. Res. 25 575(1992). 

Synthesis of disaccharides corresponding to the linkage between lipid A and KDO. 

Starting from 1,5-anhydro-2,3,4-tri-0-benzoyl-6-deoxy-D-ura >/ o-hex-1 -enitol (48), an unusual approach to the synthesis of disaccharides of serogroup A and D has applied the allylic rearrangement glycosylation procedure of Ferrier [127] to obtain an a-D-< rj//zTO-hex-2-enopyranosyl residue in the disaccharide 49a. Reduction of the 2-enopyranose double bond gave both the paratose (ribo) 49b and tyvelose (arabino) 49c products [28]. 

The activation of [bis(acyloxy)iodo]arenes with BF3 Et20 enables the conversion of protected glycals to frans-l,2-bis(acyloxy)glycosides (Scheme 17) [44]. In the presence of triflic acid, these compounds are excellent 2-acyloxygly-cosyl donors and can be utilized in situ with carbohydrate-based alcohols for the synthesis of disaccharides. 

P. Y. Goueth, G. Ronco, and P. Villa, Synthesis of ether-linked di- and trisaccharide derivatives. 1. Synthesis of disaccharides from 5,6-anhydro-D-glucose derivatives, J. Carbohydr. Chem., 13 (1994) 679-696. 

Iodine has been used to activate methyl thioglycosides for the synthesis of disaccharides.49 Similarly, it has been reported that the use of IBr allowed for the... 

SCHEME 3.15 Synthesis of disaccharide 33 using glycosyl sulfoxide. Piv, pivaloyl. 

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