Ingrid 't Hart

19 Introduc�on 1 1.5 Chemical synthesis of GSL oligosaccharides Whereas oligonucleo�des (DNA and RNA) and pep�des can be obtained by general (automated) chemical synthe�c methods, no such general method is available for oligosaccharide synthesis. Therefore, individual synthe�c strategies are required to obtain the desired oligosaccharide(s). 87,86 Controlling stereo- and regioselec�vity are key challenges in carbohydrate synthesis and various solu�ons have been developed over �me. Glycosidic linkages are formed through chemical glycosyla�on, where a glycosyl donor and acceptor are coupled in the presence of an ac�vator. Neighboring group par�cipa�on, solvent systems and temperature can influence the stereoselec�ve outcome of a chemical glycosyla�on. 87,96,97 The most efficient and robust way to obtain 1,2- trans linkages is through neighboring group par�cipa�on. The C-2 hydroxyl on the glycosyl donor is protected with an ester func�onality and the trans glycoside is formed through the dioxolenium ion intermediate (Scheme 2A). This method provides β-linked products for sugars such as glucose or galactose and α-linked products for sugar such as mannose. 87 Scheme 2. ( A ) Neighbouring group par�cipa�on by the C-2 ester provides trans products. ( B ) A chiral auxiliary provides 1,2- cis products through a trans-decalin intermediate. ( C ) The forma�on of 1,2- cis linkages can be obtained by a bulky di- tert -butyl-silane on galactose C-4 and C-6 posi�ons. Adapted from Boltje et al., 2009. 87 O OLG O O O O O O R O R O R O O O R OR 1 R 1 OH activator 1,2- trans -glycoside dioxolenium ion oxa-carbenium ion donor acceptor A O OLG O O O 1,2- cis -glycoside beta-sulfonium ion SPh Ph activator O O SPh Ph OR 1 O OLG O O O OR 1 R 1 OH activator SPh Ph O R 1 OH O S Ph Ph O OSi O OSi O O Si O OSi B C 1,2- cis -glycoside