| 摘要 |
A novel process for the synthesis of chiral hydantoins of the structure <IMAGE> (I) wherein X is fluoro or chloro, from the corresponding 6-halo-4-chromanone of the structure <IMAGE> (II) is described. The compounds I are valuable in the treatment of certain chronic complications arising from diabetes mellitus. In addition the compound of the formula I wherein X is chloro possesses complementary hypoglycemic activity. The process comprises the sequence of dehydrative coupling of the halochromanone (II) with S-(-)-alpha-methylbenzylamine to form the imine of structure <IMAGE> (III) addition of hydrogen cyanide to form the nitrile of structure <IMAGE> (IV) condensation with chlorosulfonylisocyanate (or its equivalent) to form the alpha-methylbenzylhydantoin of structure <IMAGE> (V) and finally solvolysis of the latter to the chiral hydantoin of structure I.
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