维生素B12环B酰亚胺前体及琥珀胺类药物不对称合成的研究

从γ-丁内酯合成了维生素B₁₂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TiCl₃还原硝基乙烯类化合物的反应,同时发现了一个简便合成乙琥酰胺环的新方法.

Studies on the Asymmetric Synthesis of Precursor of Vitamin B12 Ring-B Imide and Succinimide Drugs

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 in₃₆% overall yield with 94% optical purity. We established a set of conversions from(±)-3 to the precursor of Vitamin B₁₂ ring Bimide 8 under mild conditions and complete the synthesis of three derivatives of ethosuximide 6_ 8 at the same time. By remolding TiCl₃ reduction of nitroolefins the yield of 2-methyl butyrolactone-2-acetaldehyde 4 from 3 can be increased to 88%. Anew method has been found to directly construct succinimide ring from 2-methyl butyrolactone-3-acetic acid 5. The procedure of this conversion is DCCcondensation of 5 and dry benzylamine in acetonitrile catalyzed by DMAPat 0 ℃ over night.