| 摘要 |
In a process for the preparation of 6a , 9a -difluoro - 16 - methylene - 1,4 - pregnadiene-3,20-dione-11b ,17a -diol and the corresponding 11 - ketone from 6a - fluoro - 16 - methyl - 4,6-pregnadiene-3,20-dione by epoxidizing the D 16-double bond followed by splitting of the 16a , 17a -oxido steroid with the formation of a 16-methylene group, microbiologically introducing an 11-hydroxyl group, introducing a 9a -fluorine atom, introducing a D 1-double bond, and optionally oxidizing the 11-hydroxy compound to the 11-keto compound, the microbiological 11-hydroxylation is carried out first and the epoxidation after the D 1-dehydrogenation, whereby the yield is improved. In examples (1) the starting material is 11a -hydroxylated with Metarhizium anisopliae, the 11a -ol is D 1-dehydrogenated with 2,3-dichloro-5,6-dicyano-benzoquinone or Corynebacterium simplex, the product is converted to the 16a ,17-epoxide and this is split to 6a - fluoro - 16-methylene - 1,4 - pregnadiene - 11a ,17a - diol-3,20-dione, this is dehydrated to the D 9(11)-compound and this converted via the 9b , 11b -epoxide to the required 9a -fluoro-11b -ol, and this is oxidized to the 11-one; (2) the starting material is 11b -hydroxylated with Curvularia benata, the 11b -ol is dehydrated to the D 9(11)-compound, this is D 1-dehydrogenated with dichlorodicyanobenzoquinone, or selenium dioxide or Corynebacterium simplex, the product is epoxidized and split and the resulting 6a -fluoro - 16 - methylene - 1,4,9(11) - pregnatrien-17a -ol-3,20-dione is converted as in (1) to the 9a -fluoro-11b -ol; (3) the D 1,4,16-pregnatrien-11a -ol prepared in the second stage of (1) is converted via the 11-tosylate to 6a -fluoro-16-methyl - 1,4,9(11),16 - pregnatetraene - 3,20-dione which is then converted to the required product as in (1) and (2); and (4) the 11b -ol prepared in the first stage of (2) is dehydrogenated to 6a - fluoro - 16 - methyl - 1,4,16-pregnatrien-11b -ol-3,20-dione and this is then dehydrated and converted to the required product.
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