NOVEL RESOLUTION PROCESS FOR RACEMIC SPIRO-HYDANTOINS.

摘要

A NOVEL THREE- STEP PROCESS FOR RESOLVING A RACEMIC SPIRO- HYDANTOIN COMPOUND INTO ITS OPTICAL ANTIPODES IS DISCLOSED WHICH INVOLVES (1) REACTING SAID RACEMIC COMPOUND WITH AN OPTICALLY- ACTIVE ASYMMETRIC ISOCYANATE OF THE FORMULA RNCO, WHEREIN R IS (S)- OR (R)- 1- PHENYL- ETHYL OR (S)- OR (R)- 1-(1-NAPHTYHL) ETHYL, TO FORM THE CORRESPONDING DIASTEREOMERIC UREIDO COMPOUND; (2) SEPARATING THE RESULTING DIASTEREOMERIC MIXTURE INTO ITS COMPONENT PARTS, AND (3) THEREAFTER COVERING THE SEPARATED UREIDO DIASTEREOMERS OBTAINED IN STEP (B) TO THE CORREPONDING ASYMMETRIC HYDANTOIN COMPOUNDS BY TREATMENT WITH AN ALKALI METAL LOWER ALKOXIDE (C1- C4) FOLLOWED BY ACIDIFICATION WHEREUPON THE DESIRED OPTICAL ISOMER IS OBTAINED. THE FINAL PRODUCTS SO OBTAINED, SUCH AS (4S)-(+)- 6- FLUORO- 2, 3- DIHYDRO- SPIRO-[ 4H-1 BENZOPYRAN- 4, 4''- IMIDAZOLIDINE]- 2'' , 5''- DIONE (SORNIBIL) AND (5''S)- 3''- CHLORO-5'', 6'' 7'' 8''= TETRAHYDRO- SPIRO [ IMIDAZOLIDINE-4, 5''- QUINOLINE]- 2,5- DIONE ARE KNOWN TO BE USEFUL IN PREVENTING OR ALLEVIATING CERTAIN CHRONIC DIABETIC COMPLICATIONS. THE AFORE- MENTIONED DIASTEREOMERIC UREIDO INTERMEDIATES ARE NOVEL COMPOUNDS.