Ingrid 't Hart

80 Chapter 4 4 Compound 22 was acetylated by treatment with ace�c anhydride in pyridine to provide compound 23 (81%). The anomeric TDS group was cleaved by HF·Pyridine to provide lactol 24 , which was converted into trichloroace�midate 8 by reac�on with trichloroacetonitrile in the presence of Cs 2 CO 3 (81%, 2 steps: Scheme 3). Scheme 3. Chemical synthesis of GlcNAc-II trichloroace�midate donor 8 . Reagents and condi�ons: (a) i. Ac 2 O, Pyridine, ii. HF·Pyridine, Pyridine; (b) i. NCCCl 3 , DBU, CH 2 Cl 2 , 0 °C; (c) ClC(NPh)CF 3 , Cs 2 CO 3 , CH 2 Cl 2 , 0 °C to r.t., 4 Å MS. Chemical glycosyla�on of donor 8 and acceptor 9 provided disaccharide 13 in a high yield (72%). The acetyl esters was easily removed under Zemplén condi�ons ( cat . NaOMe, MeOH) to form disaccharide acceptor 11 (Scheme S1). Galactose donor 7 contains flexible protec�ng groups to furnish neighbouring group par�cipa�on (OBz), acceptor forma�on (OLev) and a sulfa�on site (ONap) (Scheme 4). Star�ng from compound 25 30 , the C-2 hydroxyl was protected by a benzoyl ester ( 26 , 80%). Next, selec�ve opening of the benzylidene by TFA and Et 3 SiH in DCM at 0 °C, smoothly provided compound 27 . Protec�on of the C-4 hydroxyl of compound 27 by treatment with levulinic acid in the presence of EDC/DMAP/Et 3 N resulted in 50% conversion to 28 . Silica column purifica�on provided 28 and star�ng material 27 , which was submi�ed for Lev protec�on once more, providing a total yield of 75% of compound 28 . The axial hydroxyl of galactose is known to have a low reac�vity, especially when bulky electrophiles are used. 31 Scheme 4. Chemical synthesis of Gal-III donor 7 . Reagents and condi�ons: (a) BzCl, pyridine; (b) i. TFA, CH 2 Cl 2 , 0 °C, ii. LevOH, EDC, DMAP, Et 3 N; (c) i. TFA, NIS, H 2 O ii. DBU, CH 2 Cl 2 , 0 °C. Ini�ally, thioglycoside donor 28 was used for a glycosyla�on with acceptor 11 employing NIS/TfOH as the promotor system at 0 °C or -30 °C. However, in both cases an inseparable anomeric mixture of 14 was formed. Therefore, donor 7 was synthesized from compound 28 by subsequent hydrolysis of the anomeric thiol ether by NIS/TFA/H 2 O and forma�on of the trichloroace�midate (Scheme 4). Glycosyla�on of donor 7 with acceptor 11 at -70 °C provided 14 as product, which was confirmed to be the β-anomer by 1D and 2D NMR spectroscopy (Scheme S2). O O O NapO OR SPh Ph O OBn LevO NapO OBz O CCl 3 NH O BnO HO NapO OBz SPh O BnO LevO NapO OBz SPh b b 25 : R = H 26 : R = Bz, 80% 27 , 95% 28 , 75% 7 , 54% c e O NPhth BnO HO BnO OTDS O NPhth BnO AcO BnO O CCl 3 NH O NPhth BnO AcO BnO OTDS a b 23, 81% 24 , 90% 8, 90% 22 c O NH 2 HO HO HO 8 steps OH HCl