Hydrochloric Acid → HCID 5358230, compound

Participants

Reaction Conditions

Reaction Steps

In 800 ml of anhydrous tetrahydrofuran (THF) is dissolved 15.0 g of antibiotic Ansamitocin mixture (12% of Ansamitocin P-2, 71% of P-3 and 17% of P-4) and, under dry nitrogen gas streams, the solution is cooled to -50° C. in a dry ice-ethanol bath. Then, 13.0 g of lithium aluminum hydride (LAH) is added at one stroke and the mixture is stirred at a temperature from -50° C. to -22° C. for 2 hours. Then, at -28° C., a further 3 g of LAH is added and the reaction mixture is stirred at -28° C. to -22° C. for 80 minutes. Thereafter, at -50° C., 750 ml of 2 N HCl is added dropwise with caution and the reaction mixture is extracted three times with 2.6 l, 1.6 l and 0.8 l portions of ethyl acetate. The extracts are pooled, washed twice with a 100 ml each portion of saturated aqueous solution of sodium chloride and dried (MgSO4 , 250 g). The solvent is distilled off under reduced pressure and the residue (13.6 g) is chromatographed on a column of silica gel (1.2 kg), elution being carried out with ethyl acetate-water (98.5:1.5, V/V). The eluate is collected in 400-gram fractions. Fractions 35 through 52 are pooled, the solvent distilled off and the residue dried in vacuo to obtain 7.25 g of maytansinol. Then, fractions 53 through 68 are similarly treated to obtain 1.55 g of a substantially equimolar mixture of maytansinol and dechloromaytansinol. Similarly, fractions 69 through 86 yield 0.78 g of dechloromaytansinol.

Provenance & Evidence