Reaction Steps
(From Mandal et al, J. Med. Chem. 2009, 52, 6126-41) To a solution of oxalyl chloride (8.0 mmol) in 30 mL of dry CH2Cl2, stirred at −78° C. under argon was added DMSO (16.0 mmol) via syringe dropwise with vigorous stirring. After 20 min, a solution of Fmoc-D-threoninol benzyl ether (5.0 mmol) in 20 mL of dry CH2Cl2, was added while maintaining the bath temperature at −78° C. Stirring was continued further for 30 min. Dry and distilled DIEA (30 mmol) was then added using a syringe and the reaction mixture then allowed to warm to room temperature without removing bath. The reaction mixture then quenched with 20 mL of ice-cold water and extracted with CH2Cl2 (3×80 mL). The combined organic layers were washed with 1N HCl (3×30 mL), brine (1×30 mL) and dried (MgSO4) and concentrated under vacuum. The crude aldehyde was used immediately for the next step without characterization. A mixture of the Fmoc-amino aldehyde (4.0 mmol) and benzyl (triphenylphosphoranylidene)-acetate (4.4 mmol) in dry CH2Cl2 (20 mL) was stirred for 3 h. The progress of the reaction was monitored by thin layer chromatography. After completion the solvent was removed in vacuo and the residue was purified by silica gel chromatography using EtOAc in hexane. Yield: 1.55 g (68%), white powder. 1H NMR (CDCl3, 300 MHz) δ 1.22 (d, J=5.7 Hz, 3H), 3.7 (m, 1H), 4.2 (t, J=6.6 Hz, 1H), 4.3-4.45 (m, 4H), 4.58 (d, J=11.7 Hz, 1H), 5.2 (s, 2H), 5.98 (d, J=15.3 Hz, 1H), 6.98 (m, 1H), 7.28-7.38 (m, 14H), 7.58 (d, J=7.5 Hz, 2H), 7.74 (d, J=7.5 Hz, 2H). 13C NMR (CDCl3, 75 MHz) δ 16.5, 47.3, 66.3, 66.9, 71.1, 75.1, 120.0, 121.7, 125.0, 127.0, 127.7, 127.8, 127.9, 128.3, 128.5, 128.6, 135.9, 137.7, 141.3, 143.8, 143.9, 147.2, 165.8. Anal (C35H33NO5) C, H, N: Calc'd: C, 76.76; H, 6.07; N, 2.56. Found: C, 76.61; H, 6.06; N, 2.55. HRMS (M+H) Calc'd: 548.2437. Found: 548.2451.
