Glycosylation inverse procedure

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... 

The efficiency of this approach could be demonstrated in a-fucosylation with donor 32a and the acceptors 19C and 33A-D (Table XXXIII). Thus, with the help of this inverse procedure, the versatile building blocks for syntheses of the Lea, Le, Ley, and H antigen determinants are readily accessible (176). Presumably, this procedure may become of general importance when reactive glycosylating agents are employed. Alternatively, the reactivity of the fucosyl donor could be decreased, as has been recently proven very successfully (177). 

Schmidt, R R, Toepfer, A, Glycosylimidates, 50. Glycosylation with highly reactive glycosyl donors efficiency of the inverse procedure. Tetrahedron Lett., 32, 3353-3356, 1991. 

For the synthesis of the block, 36 was glycosylated with 34 using the inverse procedure [10] affording a high yield of disaccharide (37) (Scheme 5.6). Reductive ring-opening of the benzylidene acetal gave the 4-OH derivative (38), which was coupled with the imidate (35) to yield the trisaccharide block (32). 

Oligosaccharide synthesis with tri-chloroacetimidates] general aspects, 290 glycopeptide, 306 glycosyl phosphates, 294, 307, 308 hexasaccharide, 299 inverse procedure, 294 kinetic, thermodynamic effects, 293 Lewis acid catalysis, 289 neighboring group participation,... 

Another interesting solvent effect is associated with the application of the inverse procedure (IP) which consists of the addition of the glycosyl donor to a mixture of acceptor and acid catalyst [47,48]. In this way, particularly with highly reactive glycosyl donors often dramatic glycosylation yield improvements could be obtained [49]. This result seems to be based on a cluster effect between the catalyst and acceptor molecules hence, on penetration of the donor into this cluster, activation of the donor and following glycoside bond formation takes place within the cluster in a practically intramolecular fashion. Obviously, this effect is critically dependent on the acceptor type, the solvent, and the temperature therefore it requires often some experimentation for its successful application. 

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. 

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