ChemicalBook CAS DataBase List DM4

DM4 synthesis

6synthesis methods

Product Name:DM4
CAS Number:796073-69-3
Molecular formula:C38H54ClN3O10S
Molecular Weight:780.37

A solution of N-methyl-N-(4-methyldithio-4-methyl-1-oxopropyl)-L-alanine (36.6 mg, 0.313 mmol) and 1,3-dicyclohexylcarbodiimide (13.51 mg, 0.065 mmol) was prepared in CH2Cl2 (0.5 mL) in a round bottom flask equipped with a stir bar and maintained under an argon atmosphere. The solution stirred vigorously at room temperature for 30 minutes as the symmetrical anhydride formed. The reaction mixture was filtered through glass wool and added to a reaction flask containing maytansinol (12.3 mg, 0.022 mmol) and zinc bis[bis(trimethylsilyl)amide] (42.5 mg, 0.109 mmol) prepared in CH2Cl2 (1 mL). The reaction proceeded at room temperature under an argon atmosphere with stirring. After 3 hours, an additional 5 equivalents of zinc bis[bis(trimethylsilyl)amide] (42.5 mg, 0.109 mmol) were added to the reaction vessel and the reaction proceeded overnight. Analytical thin layer chromatography (Analtech Uniplate, 2.5×10 cm, 250 micron), eluting in a mixture of methylene chloride and methanol (95:5, v/v) indicated the formation of the desired N-methyl-L-alanyl ester of maytansinol at C3. The degree of conversion of the reaction was determined by analytical HPLC analysis using a Vydac protein & peptide C18 column (4.6×250 mm) at a flow rate of 1.50 mL/min, eluting with a gradient of water and acetonitrile, as follows: Time (min) % A (water) % B (acetonitrile) 0 95 5 2.5 95 5 32 5 95 35 5 95 Under these conditions the thiol containing product eluted at 20.75 min with no detected D-isomer. MS: m/z found 780.8 (M+Na+) calculated 781.4.