Synthesis Of Substituted Tramiprosates From α,β-Unsaturated Amides

Tramiprosate,3-amino-1-propanesulfonic acid, is a kind of naturallyoccurring amino acid, which can be artificially synthesized successfully.It is always used to cure Alzheimer’s disease for its great biologicalactivities of neuroprotect and inhibition of brain cell. For researching ofbiological activities affected by substituents, the synthesis of substitutedtramiprosate becomes an important subject. There are some shortages inthe methods reported, so we proposed a new way to meet the needs of thesynthesis of substituted tramiprosate.The method we developed is as follows: we adopt α,β-unsaturatedamides as starting materials which is easier to get relative to the materialsused in the methods reported. And the α,β-unsaturated amides arecommercial available or can be produced from α,β-unsaturated acid viaan easy way. Then, the amides took place Michael reaction withthioacetic acid to introduce sulfur to the compouds and gainedthiolacetate compouds. The intermediates obtained were reduced bylithium aluminium hydride to give aminothiols and followed by oxidation with peroxy acid. Finally, the substituted amino sulfonic acids weregained. And the method has good applicability for synthesis of differentsubstituted tramiprosates.In this paper, eleven α,β-unsaturated amides with differentsubstituents participated in the reactions, and we explored the reactionconditions. Besides, we had further research and discussion oncinnamamide which was not good at addition. Through this method, wesynthesized1-alkyl substituted,2-alkyl substituted,2-aryl substituted,1,2-disubstituted, N-substituted, N,N-disubstituted，1,N-disubstituted，2,N-disubstituted and nonsubstituted tramiprosates successfully.