维生素B_(12)环B酰亚胺前体及琥珀胺类药物不对称合成的研究

Studies on the Asymmetric Synthesis of Precursor of Vitamin B_(12) Ring-B Imide and Succinimide Drugs

从γ-丁内酯合成了维生素 B1 2 环 B酰亚胺前体及琥珀酰胺类药物的 3个衍生物 ,进行了其中不对称季碳的构筑 ,改进了 Ti Cl3还原硝基乙烯类化合物的反应 。

From γ butyrolactone 1, we synthesized ( S ) 2 methyl 2 nitroethenyl butyrolactone ( S ) 3 by the mean of direct enantioselective construction of molecule with quaternary carbon stereocenter on the bases of our previous research. ( S ) 3 was obtained in 36% overall yield with 94% optical purity. We established a set of conversions from(±) 3 to the precursor of Vitamin B 12 ring B imide 8 under mild conditions and complete the synthesis of three derivatives of ethosuximide 6_8 at the same time. By remolding TiCl 3 reduction of nitroolefins the yield of 2 methyl butyrolactone 2 acetaldehyde 4 from 3 can be increased to 88%. A new method has been found to directly construct succinimide ring from 2 methyl butyrolactone 3 acetic acid 5. The procedure of this conversion is DCC condensation of 5 and dry benzylamine in acetonitrile catalyzed by DMAP at 0 ℃ over night.