m-Chloroperbenzoic acid → Cryptophycin-292

Participants

Reaction Steps

A solution of Cryptophycin 289 (13.2 g, 20.2 mmol) in chloroform (43 mL) is stirred and treated with m-chloroperbenzoic acid (m-CPBA) (95% pure, 5.19 g, 30.1 mmol). After stirring overnight at room temperature, the solution is diluted with chloroform until clear, washed with sodium bicarbonate (saturated aqueous, 100 mL), sodium sulfite (saturated aqueous, 100 mL), sodium chloride (saturated aqueous, 100 mL), dried (magnesium sulfate), filtered, and the filtrate evaporated (40° C., 20 mm Hg) to provide 14 g of the Cryptophycin-292 as a mixture of epoxide isomers, as a white foam. The foam is dissolved in chloroform, cooled to −63° C., and treated with chlorotrimethylsilane (23.5 mL, 185 mmol) via syringe. The mixture is stirred at −63° C. for 5 hours, then allowed to stand in the freezer at −20° C. overnight. The mixture is again cooled to −63° C. and treated with sodium bicarbonate (saturated aqueous, 60 mL) with vigorous stirring. The cold bath is removed and the mixture allowed to warm to room temperature over a 1 hour period. The layers are separated and the aqueous layer extracted with chloroform. The organic layers are washed with sodium bicarbonate (saturated aqueous, 60 mL), sodium chloride (saturated aqueous, 100 mL), dried (magnesium sulfate), filtered, and the filtrate evaporated to 14 g of a white residue. The residue is chromatographed on silica gel (70×160 mm of silica gel, packed and eluted in 2:1:1 tBuOMe/CH2Cl2/hexanes) to provide 4.51 g of Cryptophycin 296 as a colorless foam (32%)

Provenance & Evidence