Glycosyl trichloroacetimidate

Trichloroacetonitrile reacts with glycosidic hydroxy groups of protected sugars to form glycosyl trichloroacetimidates (R. R. Schmidt, 1980, 1984,1985,1986 B. Wegmann, 1988). The imidate is substituted by alcohols in the presence of trimethylsilyl trifluoromethanesulfonate... 

Glycosyl trichloroacetimidate donors in the presence of selenoglycoside acceptors can be used with triethylsilyl triflate as promoter. 

This review covers the recent advances in the use of O-glycosyl imidates in oligosaccharide and glycoconjugate synthesis, with emphasis on literature published between 1999 and 2006. However, because of the large volume of work in this area, only the most representative applications will be presented. One can refer to the similar preceding review [381] published in 2000 and another quite comprehensive review [375] on trichloroacetimidate method published in 1994 for earlier application of glycosyl trichloroacetimidates. Trifluoroacetimidate method will be discussed separately in this review in the light of its less popularity in carbohydrate chemistry. 

Conventionally, the use of NaH or Cs2C03 as a base for the reaction of glycosyl hemiacetals with C13CCN often yields the thermodynamically favored a-glycosyl trichloroacetimidates, whereas the use of K2C03 often yields kinetically controlled P-glycosyl trichloroacetimidates (Scheme 3.26). The use of l,8-diazabicyclo[5.4.0] undec-7-ene (DBU) often provides a/p mixtures, mostly favoring a-products. 

In addition, the fulvestrant could be glycosylated effectively at its 17-OH position with pivaloylated glycosyl trichloroacetimidates, which suppressed the competing transacylation side reaction and led to improved yields of the desired glycosides (Scheme 3.48d) [503]. In this synthesis, the inverse procedure (i.e. addition of a trichloroacetimidate donor to a mixture of an acceptor and a promoter) was found to be superior for glycosylations. Very recently, a stepwise synthesis of branched... 

Typical Procedure for the Glycosylation with O-Glycosyl Trichloroacetimidates... 

Ultimately the significance of the 0-glycosyl trichloroacetimidates must be based solely on their glycosylation potential under mild acidic catalysis. This potential has indeed been confirmed overwhelmingly in various laboratories and is presented in comprehensive detail in this article. 

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... 

Accordingly, phosphoric acid mono- and di-esters permit uncatalyzed glycosyl transfer from 0-(glycosyl)trichloroacetimidates (52a,55-57,58a,58b). The reaction is thus very useful in the synthesis of glycophos-pholipids (1,55), which are important constituents of cell membranes (1). Commonly, direct phosphorylation at the anomeric hydroxyl group leads to... 

The great interest in C-glycosyl compounds is reflected in the extensive research in this field (204). Successful investigations with O-glycosyl trichloroacetimidates as glycosyl donors and phenol ethers (199,207,208), silyl enol ethers (205,206), trimethylsilyl cyanide (205,206), and allyltrimethylsi-lane (206) as C-acceptors underline the wide scope of these highly reactive glycosyl donors. 

The first application of (9-glycosyl trichloroacetimidates as glycosyl donors for the glycosylation of an acceptor attached to Merrifield resin was reported by our group in... 

A major contribution to the use of glycosyl trichloroacetimidates in the solid-phase synthesis of oligosaccharides came from the group of T. Ogawa (Scheme 4.7).5... 

To date, heptasaccharide 47 is the largest oligosaccharide assembled on a solid support using only monosaccharide building blocks. This turns out to be an excellent demonstration of the efficiency of the (9-glycosyl trichloroacetimidate approach. 

Glycosyl Trichloroacetimidates Attached to the Solid Support via Silyl Linkers... 

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