Trichloroacetimidate procedure

In another application of catalytic glycosylation with triflic acid, two disaccharides were synthesized with donors bearing trichloroacetimidate function and then the disaccharides thus prepared were condensed in a similar manner to a tetrasaccharide757 (1,2-dichloroethane, 55°C, 1.5 h, 50-85% yields). The same protocol was used in the synthesis of a decasaccharide from mono-, tetra-, and pentasaccharide building blocks.758 The trichloroacetimidate procedure has been successfully used in the glycosylation of /3-cyclodextrins promoted by triflic acid.759 760... 

Grundler, G. and Schmidt, R. (1984) Glycosyl imidates, 13. Application of the trichloroacetimidate procedure to 2-azidoglucose and 2-azidogalactose derivatives. Liebigs Ann. Chem., (11), 1826-1847. 

The trichloroacetimidate procedure has been reviewed at various stages of its development [12,318-320],... 

Chemical 5-thioglycosylation has largely relied on the trichloroacetimidate procedure as exemplified by Pinto and co-workers of 1,2- as well as 1,6-connected gluco-disaccharides with the thiosugar at the non-reducing end [145]. Several examples of classical Koenigs-Knorr methodology have also been reported, just to mention the most frequently employed approaches. 

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... 

Glycosylation of the free hydroxyl-functions of the polymer-bound peptides 62-65 was achieved by the trichloroacetimidate glycosylation procedure.13 After glycosylation using the first donor, the perbenzoyl-D-galactosyltrichloroacetimidate... 

Trichloroacetimidates, CCl,C(NH)OR, have been prepared under mild conditions by the reactions of alcohols with trichloroacetonitrile under basic conditions promoted by catalytic amounts of tetra-n-butylammonium hydrogen sulphate [72]. The procedure is far superior to the standard methods which normally require anhydrous reaction conditions. 

Before this acid could be used in lipid A synthesis, its 3-hydroxyl group had to be protected most preferably by benzylation. This was performed as shown in Figure 6. Of the two benzylating procedures, that with trichloroacetimidate described recently by Iversen and Bundle (9) was preferable because of the shorter reaction time needed. Since this hydroxyl group is on the 3-carbon atom of the carboxyl function, strong alkali such as NaOH could not be used as it caused 3-elimination of benzyl alcohol from the product (J ). 

After developing procedures for the activation and coupling of anomeric trichloroacetimidate and glycosyl phosphate donors as well as for the deprotection of acetyl and levulinoyl esters, we designed a synthesis utilizing all aspects of our automated chemistry. Trisaccharide 24, composed of three... 

The high reactivity of glycosyl trichloroacetimidate can lead to side reactions or even decomposition of the donor before reaction with the acceptor. To improve yield and the stereocontrol of the reaction, the so-called inverse glycosylation procedure is often used. In this case the glycosyl acceptor and the catalyst are dissolved together followed by the addition of the glycosyl donor. 

Benzylation with benzyl trichloroacetimidate and a catalytic amount of triflic acid (TfOH) is a mild and efficient procedure (Scheme 2.1c).5 The acid protonates the nitrogen of the imidate moiety converting it into a very good leaving group. Nucleophilic attack by an alcohol introduces a benzyl ether. The procedure is often compatible with base- and acid-sensitive functionalities with esters, (7-isopropylidene and (7-benzylidene acetals. Benzyl trichloroacetimidate is commercially available but can easily be prepared by reaction of benzyl alcohol with trichloroacetonitrile in the presence of a mild base. 

The next section describes briefly the procedures for the preparation of anomeric halides, trichloroacetimidates and thioglycosides and their modes of activation. 

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