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Experimental for the Formation of Molecule 63 from Molecules 14, 61, and 62

Wang, Z.-G.; Warren, J. D.; Dudkin, V. Y.; Zhang, X.; Iserloh, U.; Visser, M.; Eckhardt, M.; Seeberger, P. H.;

Danishefsky, S. J.; Behar, V.; Randolph, J. T.; Lloyd, K. O. J. Am. Chem. Soc. 1995, 117, 5701-5711.

Synthesis of Molecule 63:
A 1.00 g (3.04 mmol) sample of D-galactal derivative 61 was azeotropically dried using benzene before being dissolved in 20 mL of dry CH2Cl2 under N2. The solution was cooled to 0 ºC, and 50 mL (4.5 mmol) of 3,3-dimethyldioxirane solution was added with stirring. The solution was stirred at 0 ºC for 40 min, at which time TLC (1:1 EtOAc:hexanes) indicated no trace of 61. The solvents were evaporated using a dry N2 stream to give a 1,2-anhydro derivative, which was dried in vacuo. To the flask containing the 1,2-anhydro derivative under N2 was added, via cannula, a solution of 1.60 g (4.90 mmol) of D-glucal derivative 14, which had been azeotropically dried using benzene, in 10 mL of dry THF. The stirred solution was cooled to -78 ºC and 5.0 mL of 1.0 M ZnCl2 in Et2O was added. The mixture was maintained at -78 ºC for 2 h and then allowed to slowly warm to room temperature and stirred an additional 10 h. The reaction mixture was quenched using 50 mL of saturated aqueous sodium bicarbonate and partitioned between 50 mL of water and 100 mL of ethyl acetate. The aqueous layer was extracted twice with 100 mL of ethyl acetate. The combined organic layers were dried over MgSO4 and the crude product was purified by column chromatography on silica gel (1:3 EtOAc:hexanes. A mixture of 600 mg (0.89 mmol) of the resultant product and 1.00 g (2.29 mmol) of α-L-focusyl fluoride donor 62 was azeotropically dried using benzene and placed under N2. This mixture was dissolved in 20 mL of dry THF and 2.5 mL (11.1 mmol) of di-tert-butylpyridine, and the resulting solution was added via cannula to a flask containing 1.15 g (2.80 mmol) stannous triflate and powdered 4 Å molecular sieves (2.0 g) at 0 ºC under N2. The mixture was stirred at 0 ºC for 4 h and then partitioned between 200 mL of saturated sodium bicarbonate and 100 mL of ethyl acetate. The aqueous layer was extracted twice more with 100 mL of ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the crude product was purified by column chromatography on silica gel (1:4 EtOAc:hexanes). Trisaccharide glycal 63 was obtained as a colorless glass (0.66 g, 67%): [α]22D = -76.5 º (c 1.9, CH2Cl2); FTIR (thin film) 2940, 2865, 1816, 1650, 1454, 1366, 1245, 1168, 1100, 1050, 883, 736, 697; 1H NMR (400 MHz, CDCl3) δ 7.40-7.22 (m, 25 H), 6.32 (d, 1 H, J = 6.2 Hz), 5.02 (d, 1 H, J = 3.6 Hz), 4.96 (d, 1 H, J = 11.6 Hz), 4.86-4.78 (m, 4 H), 4.77-4.72 (m, 2 H), 4.67-4.61 (m, 2 H), 4.60-4.56 (m, 3 H), 4.53 (d, 1 H, J = 12.0 Hz), 4.45 (d, 1 H, J = 12.0 Hz), 4.12-4.03 (m, 3 H), 4.02 (m, 1 H), 3.95 (m, 1 H, J = 6.4 Hz), 3.87-3.77 (m, 5 H), 3.71 (m, 1 H, J = 5.4 Hz), 3.64-3.58 (m, 2 H), 1.09-1.00 (m. 24 H); 13C NMR (CDCl3) δ 153.74, 144.25, 138.65, 138.49, 138.44, 138.39, 137.95, 128.46, 128.37, 128.34, 128.20, 128.19, 128.17, 127.88, 127.85, 127.73, 127.60, 127.55, 127.43, 127.34, 99.83, 98.64, 97.43, 78.92, 77.46, 76.43, 76.21, 75.46, 74.78, 73.88, 73.80, 73.64, 73.39, 73.03, 72.88, 72.52, 71.42, 70.50, 67.77, 67.16, 61.53, 17.87, 17.84, 16.53, 11.76; HRMS (FAB) calculated for C63H78O14SiNa 1109.5060, found m/z 1109.5069 (M + Na).

D-galactal derivative 61:

Azeotropically dried: to remove the water from by azeotropic distillation, which involves the technique of adding another component to generate a new lower-boiling azeotrope that is heterogeneous, such as the addition of benzene to water and ethanol

Benzene: