Synthesis Of Talo-DNJ

Fabry disease is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal α-galactosidase.Recently,Galacto-DNJ has been used to cure Fabry disease clinically.At the same time,Talo-DNJ Which is the enantiomer of Galacto-DNJ has proved a inhibitor of fucosidase.According to different cyclization ways,We design intramolecular cyclization and intermolecular cycliazation.We have done some research on the double acetone fork protection and Chiral inversion of carbon atom The key step in the intermolecular cycliazation route is the α-chlorination of aldehyde but We get low yield.We continue to try many other optimization no one of which can increase the yield so that we give up this route.In the intramolecular cyclization route,we applied the steric effect upside the furanose ring to create the stereoselective reduction.we still accomplish the Misutobu reaction and selective epoxidation ring-opening.one of which can get the talo-DNJ using inner molecular cyclization.In the six-ring cyclization,one of the configurations can reaction to the galacto-DNJ by sodium hydride tetrafuran refluxing system.The other configuration get no result.We speculate the cause that the substituent group of the number two carbon prevent the formation of six-center cyclic transition state.By decresing the number of benzyl group,we accomplish the synthesis of galacto-DNJ.