Two-stage activation

The two-stage activation strategy has also been employed for the synthesis of Lewis [19-21] and globotriaosylceramide-related structures [22,23]. 

An additional version of the two-stage activation used glycosyl sulfoxides to glycosylate thioglycoside acceptors [25-28]. The thioglycosides are then readily activated as sulfoxides using oxidation with m-chloroperbenzoic acid. 

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According to the two-stage activation (or preactivation) approach, both glycosyl donor and glycosyl acceptor initially bear the same type of a leaving group (LGa). 

Figure2.7 Two-stage activation procedure using glycosyl fluoride and thioglycoside as glycosyl donor.

G. Oligosaccharide synthesis from glycosyl fluorides and sulfides and the two-stage activation procedure 317... 

H. Application of two-stage activation procedure to complex molecule synthesis 321... 

G. Oligosaccharide Synthesis from Glycosyl Fluorides and Sulfides and the Two-Stage Activation Procedure... 

The two-stage activation procedure for the synthesis of complex oligosaccharides developed in these laboratories [23] combines the chemistries of glycosyl fluorides and sulfides. It is, therefore, instructional to discuss first, the use of these two classes of glycosyl donors in oligosaccharide synthesis, before describing the two-stage activation method. 

Scheme 9 The two-stage activation procedure for glycoside bond formation [23].

H. Application of Two-Stage Activation Procedure to Complex Molecule Synthesis... 

Numerous applications of the two-stage activation procedure have already been recorded. In this chapter, we highlight schematically the synthesis of the following complex mole-... 

Hakeos, W. H., Miao, H., Sirachainan, N., Kemball-Cook, G., Saenko, E. L., Kaufman, R. J. and Pipe, S. W. (2002). Hemophilia A mutations within the factor VIII A2-A3 subunit interface destabilize factor Villa and cause one-stage/two-stage activity discrepancy. J. Thromb. Haemost. 88, 781-787. 

Nicolaou used glycosyl fluorides as donors and thioglycosides as acceptors, and the procedure took advantage of the ready conversion of thioglycosides into glycosyl fluorides with NBS and DAST [17]. The two-stage activation procedure is illustrated by the synthesis of a phytotoxic oligosaccharide (78), a member of rhynchosporosides [18] (Scheme 5.13). 

The two-stage activation procedure for oligosaccharide synthesis, which was developed by Nicolaou and applied to his synthesis of avermectin Bia [10]> was also employed in his total synthesis of efrotomycin [15] (Scheme 12.11). The chemo- and stereoselective glycosidation of the... 

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