Ingrid 't Hart

81 Chemical synthesis of sulfoglycolipid analog SM1a-core3 4 Trisaccharide acceptor 4 was obtained a�er removal of the Lev-ester by hydrazine acetate. It was noted that hea�ng (50 °C) was required to drive the reac�on to comple�on. Complete conversion to product 4 was required, since a mixture of compounds 14 and 4 was inseparable by silica column chromatography. Disaccharide 12 was synthesized from donor 5 and acceptor 6 in a similar fashion as in Chapter 2 of this Thesis. 32 Earlier studies showed that the benzylidene acetal on a Galβ1,3GalNAc disaccharide donor provided low reac�vity and poor anomeric selec�vity. 32 Also, replacement of the benzylidene for 4- and 6-O acetyl esters decreased donor reac�vity dras�cally, providing only traces of product (data not shown). Therefore, the benzylidene acetal was selec�vely opened by treatment with Cl 2 BPh and Et 3 SiH to obtain a C-4 benzyl ether and C-6 hydroxyl. The exposed C-6 hydroxyl was protected by an acetyl ester providing intermediate disaccharide 10 (55%, 2 steps). The anomeric silyl protec�ng group (TDS) was cleaved by treatment with HF·pyridine and the intermediate lactol was converted into the N -phenyl trifluoroace�midate, providing donor 3 (62%, 2 steps; Scheme S3). Glycosyla�on of disaccharide donor 3 and trisaccharide acceptor 4 successfully provided pentasaccharide 2 (40%). Deprotec�ons and sulfa�on of compound 2 will provide target compound 1 ; a sulfoglycolipid- O -glycan hybrid. SM1a-core 3 will be screened in a microarray binding study as the poten�al cancer specific an�gen HAE3. Conclusions New cancer-associated an�gens have been discovered among the sulfoglycolipids, but li�le is known about their mechanisms of ac�on. Sulfoglycolipid SM1a was detected as a ligand for the cancer specific an�body HAE3 in a glycan microarray screening. It is known that HAE3 binds mucin-type O -glycans and a search for epitopes similar to SM1a provided a set of core 3 O -glycans. Therefore, a SM1-core3 hybrid was proposed as a ligand for HAE3. Here we report the first total synthesis of a protected SM1-core3 glycan with a reducing α-aminopentyl linker for immobiliza�on. A�er global deprotec�on and sulfa�on, a microarray study will reveal the HAE3 binding proper�es to SM1-core 3. A binding interac�onwill support the presence of SM1-core 3 and similar sulfated O -glycans in the mucin glycoproteins. This will encourage the search for sulfated mucin glycans as a new class of cancer biomarkers. Furthermore, the op�mized synthe�c strategy will be useful for future synthesis of sulfoglycolipids and its analogs. Experimental sec�on Chemical synthesis NMR nomenclature The monosaccharides of glycan SM1-core3 have been labeled as shown in Figure S1. Star�ng from the reducing end these were labeled GalNAc-I, GlcNAc-II, Gal-III, GalNAc-IV and Gal-V.