0-Glycosyl trichloroacetimidates, reactions

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... 

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... 

Trichloroacetimidate Glycosyl acceptor Reaction conditions Reference... 

Even controlled-pore glass (CPG) could be successfully employed as solid support with (9-glycosyl trichloroacetimidates as glycosyl donors. Thus, limitations of solvents and reaction temperatures in the glycosylation step, as experienced with the Merrifield resin, are restricted to those observed in solution-phase synthesis. Therefore, regio- and stereocontrol of the glycosylation reactions should be available from well-established solution-phase methodologies. 

Soluble polyethylene glycol (PEG) as polymer support was also successfully investigated. Precipitation after each reaction step in order to remove excesses of reagents and soluble byproducts seemed to work well. Another topic of great interest is direct glycosylation of solid support connected peptides in order to arrive finally at glycopeptides. (9-Glycosyl trichloroacetimidates also proved successful in this endeavor. 

Besides oxygen, other nucleophiles have also been successfully employed as acceptors. For instance, N-, C-, S-, and / -glycosyl derivatives have been obtained from corresponding nucleophiles and O-glycosyl trichloroacetimidates in the presence of acid catalysts [1 ]. For instance, aryl-C-glycosjdes have been recently synthesized from phenols in an efficient Fries-type rearrangement reaction [37]. 

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. 

Hoffman, M G, Schmidt, R R, O-Glycosyl imidates. 19. Reaction of glycosyl trichloroacetimidates with silylated C-nucleophiles, Liebigs Ann. Chem., 2403-2419, 1985. 

In the first part of this review, the basic principles of chemical glycosylation reactions are discussed this way the advantages of 0-glycosyl trichloroacetimidates and related systems as glycosyl donors become obvious. Many new methods for the generation of 0-glycosyl trichloroacetimidates and for their use as glycosyl donors have been introduced which are... 

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