| Spiro compounds have rigid construction for its two perpendicular ring plane. As far as the spiro heterocycle compounds are concerned, spiroconjugation, spirohyper- conjugation and anomeric effect are the unique properties. In recent years, spiro compounds have an extremely important position in modem organic synthesis, which are of high value in medicine, asymmetric catalysis, luminescent materials, photo chromic materials, pesticides, adhesives and other polymer applications. Research shows that, the special space configurations can usually match different spatial structure of macromolecules in organisms, and therefore show significant biological activity So more and more parent structures of spiro compounds have attracted attention in the field of drug development.In this thesis, we have designed and synthesized the new thiaspiro compounds:6-amino-2-thiaspiro[3,3]heptane hydrochloride (conmpound 10) and 6-amino-2-oxaspiro[3,3]heptane hydrochloride (compound 13). By using 2,2-bis(bromo-methyl)-1,3-propanediol as the start material, via acetal reaction, esterification, hydrolysis, decarboxylation, Curtis rearrangement reaction, hydrogenation, methyl sulfonylation, cyclization and Boc elimination reaction to give compound 10. The compound 10 was synthesized in nine steps in 30.7% overall yield, the average total yield was 20.9%.In addition, we have studied the synthesis of 6-amino-2-oxaspiro[3,3]heptane hydro-chloride. the intermediate 1-tert-butoxycarbonylamino-3,3-bis(hydroxymethyl)cyclobutane (compound 7) through a mono-mesylation to give 3-(tert-butoxycarbonylamino)cyclobutane-1,1-diylbis(methanesulfonate) (compound 11). After viaing cyclization and Boc elimination reaction,2-oxaspiro[3,3]heptane derivative, the target compound 13 could be obtained.We designed the synthetic routes of these compounds, and optimized them based on our extensive work. The route has the advantages of simple operation, high yield, good for the environment and suitable for large-scale development. |
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