申请人:PFIZER INC.
公开号:EP0352959A1
公开(公告)日:1990-01-31
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-phenylethyl or (S)- or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric ureido compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diastereomers obtained in step (b) to the corresponding 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 (sorbinil) 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 aforementioned diastereomeric ureido intermediates are novel compounds.
本发明公开了一种将外消旋螺海因化合物分解为其光学对映体的三步法新工艺,包括 (1) 将所述外消旋化合物与式 RNCO 的光学活性不对称异氰酸酯反应,其中 R 为(S)-或(R)-1-苯基乙基或(S)-或(R)-1-(1-萘基)乙基,形成相应的非对映脲基化合物;(2) 将得到的非对映异构体混合物分离成各组分,以及 (3) 随后通过碱金属低级烷氧化物(C₁-C₄)处理,将步骤(b)中分离得到的脲基非对映异构体转化为相应的不对称海因化合物,然后进行酸化,从而得到所需的光学异构体。这样得到的最终产物,如(4S)-(+)-6-氟-2,3-二氢-螺[4H-1-苯并吡喃-4,4′-咪唑烷]-2′,5′-二酮(sorbinil)和(5′S)-3′-氯-5′、6′,7′,8′-四氢-螺[咪唑烷-4,5′-喹啉]-2,5-二酮,可用于预防或减轻某些慢性糖尿病并发症。上述非对映脲中间体是新型化合物。