反应详情

A diamine side chain is first synthesized in a manner analogous to the side chain of quinacrine. Specifically, mono-phthaloyl protected 1,4-diaminobutane (27) is reacted with 6,9-dichloro-2-methoxyacridine (28) in phenol (J. Am. Chem. Soc. 66:1921-1924, 1944). The reaction mixture is then poured into an excess of 2 N NaOH and extracted with ether. The ether extract is washed with 1 M NaHCO3, then H2O, and dried over MgSO4. The crude product is recrystallized from H2O-alcohol. The phthaloyl protecting group is removed using anhydrous hydrazine in MeOH (Bioconjugate Chem. 2:435-440, 1991) to yield the aminoacridine, (29). Aminoacridine (29) is then conjugated with vitamin B12 monocarboxylic acid (2, 3, 4) to yield a cyanocobalamin-acridine conjugate (30).

1. extractionextracted with ether
2. extractionThe ether extract
3. washis washed with 1 M NaHCO3
4. dry with materialH2O, and dried over MgSO4
5. customThe crude product is recrystallized from H2O-alcohol
6. customThe phthaloyl protecting group is removed