The Trichloroacetimidate Method

In basic medium, the kinetic derivative 44 eq is slowly transformed into the thermodynamically more stable 44 ax, which is obtained as single product using NaH as base. In contrast, the use of a weak base such as potassium carbonate allows isolation of the (f-trichloroacetim-idate in good yield. The (5- and the a-trichloroacetimidates are stable adducts which can be directly isolated and easily stored [139]. 

8 Selective Glycosidation Reactions and Their Use in Medicinal Chemistry 

A dramatic effect has recently been observed in the case of nitriles as participating solvents in glycoside reactions [140,141], In these solvents, a high preference for (5 glycosidation was noticed. 

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The trichloroacetimidate method has also been used to prepare bivalent Lex oligosaccharides to study the conformational details of carbohydrate clusters by NMR spectroscopy [437] TWo Le trisaccharides were covalently linked through... 

The trichloroacetimidate method has also found wide applications in the synthesis of various complex oligosaccharides. In the course of the development of chemically defined glycoconjugate vaccines against shigellosis, a decasaccharide, corresponding to two consecutive repeating units of the O-specifk polysaccharide of Shigella... 

Scheme 3.52), whereas the corresponding acetyl-protected donor gave little product under the same reaction conditions [512], Additionally, the trichloroacetimidate method has also been applied to synthesize other natural products, such as bupres-tin A and B [517], macrophylloside D [518] and neomycin mimetics [519]. 

In addition, a novel fluorous support has been developed recently as an alternative to traditional polymer supports and applied successfully to oligosaccharide synthesis in combination with the trichloroacetimidate method [541]. Each intermediate in the fluorous oligosaccharide synthesis [542,543] could be obtained by simple fluorous-organic solvent extraction, and the reactions could be monitored by TLC, NMR and MS, in contrast to solid-phase reactions. Moreover, the new liquid-phase technique is anticipated to be easily applicable to the large-scale synthesis. 

ANOMERIC-OXYGEN ACTIVATION FOR GLYCOSIDE SYNTHESIS THE TRICHLOROACETIMIDATE METHOD... 

The trichloroacetimidate method for glycoside synthesis extended its versatility right at the outset (51,52a) by exhibiting an especially smooth reaction of 0-(glycosyl)trichloroacetimidates with Bransted acids. Without the addition of any catalyst, simple Bransted acids are able to substitute the trichloroacetimidate group at room temperature in high yields, as shown (17) for la-a in Scheme 6. Because of anomerization of possible / products... 

The requirements for new glycosylation methods outlined at the beginning of this chapter, namely convenient diastereocontrolled anomeric O-ac-tivation (first step) and subsequent efficient diasterecontrolled glycosylation promoted by genuinely catalytic amounts of a catalyst (second step), are essentially completely fulfilled by the trichloroacetimidate method. This is clearly shown by the many examples and references given in this article. In terms of stability, reactivity, and applicability toward different acceptors, the... 

II. THE TRICHLOROACETIMIDATE METHOD A. Trichloroacetimidate Formation (Activation Step)... 

J. Rademann and R. R. Schmidt, Solid-phase synthesis of a glycosylated hexapeptide of human sialophorin, using the trichloroacetimidate method, Carbohydr. Res. 269 217 (1995). 

High a-selectivities were observed when the D-galactosyl donor 10 was used for the coupling with secondary hydroxy groups in carbohydrate acceptors including 9 (see Scheme 5). With the trichloroacetimidate method [5], the yields of disaccharides derived from 6 and 7 were 85% (10 1, a/p) and 87% (only a), respectively. The condensation of 10... 

This is the first glycosylation in this synthesis. There are several methods to build a new glycosydic C-O bond. Very important methods are the Koenigs-Knorr25 and related reactions and the trichloroacetimidate method.26 It depends on the carbohydrates themselves, what kind of method is useful and which donor and acceptor you have to use. 

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