Synthesis Of1-substituted Homotaurines From Acrylonitrile Derivatives

Homotaurine is a candidate drug for treating Alzheimer’s disease and re-searchers have completed a phase Ⅲ clinical trial. Although the effect oftreating AD was controversial, the potential treatment effects of homotaurinefor other diseases should be investigated in the future. And homotaurine hasbeen reported that it is an inhibitory aminoacids with anticonvulsant propertiesagainst various experimental models of focal epilepsy. Some biological activi-ties of homotaurine derivatives have been understood. So it’s necessary to finda new way to synthesize homotaurine and its derivatives. At present there aresome preparation methods of homotaurine and its derivatives, but the methodshave some disadvantages in separation and purification. The efficient syntheticmethod is still scattered.This dissertation developed a new method to synthesize1-substituted homo-taurines. First a series of acrylonitriles was synthesized from aldehydes or ke-tones. The underwent sulfur-Michael addition reaction with different sulfurnucleophiles yields the corresponding cyanoalkylthioacetates in satisfactory togood yields. Then the cyanoalkylthioacetates were reduced to aminothiols byLiAlH4. In the following step the aminothiols were oxidized by peroxy formic acid to afford a serie of1-substituted homotaurines in high yields.The present method is appropriate for synthesizing aliphatic and aromatic1-substituted homotaurines. This method has a lot of advantages such as easilygetting reactants, short steps, high yield, salt-free, high universality. It is acommon synthetic method of1-substituted homotaurine derivatives.