Improvements in or relating to 5,10-seco-5,19-cyclo-10-fluoro-steroids

摘要

The invention comprises compounds of the formulae wherein R is hydrogen or a hydrocarbon carboxylic acyl radical of less than 12 carbon atoms which may be substituted; R1 is hydrogen, alkyl, alkenyl or alkynyl of at most 6 carbon atoms; Z is a single or double bond between C-1 and C-2 and Z1 is a single or double bond between C-6 and C-7, with at least one of Z and Z1 being a double bond; and Y is hydrogen, b -hydroxy or keto. The androstane derivatives are prepared by dehydrogenation of 5,10-seco - 5,19 - cyclo - 10b - fluoro - D 4 - androsten-17b -ol-3-one or the 17a -R1 homologues thereof. The D 1,4-compounds are prepared by refluxing these starting materials with selenium dioxide in t-butanol in the presence of pyridine or with 2,3 - dichloro - 5,6 -dicyano - 1,4 - benzoquinone, and on a second dehydrogenation with chloranil in t-butanol or with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, these are converted to the D 1,4,6-compounds. When the reaction with chloranil is effected first the D 4,6-compounds are obtained. The same starting materials or the corresponding 3,17-dione yield on reduction, preferably with lithium aluminium hydride in tetrahydrofuran, the corresponding 3,17-diols, which on dehydration with aqueous acetic acid at 75 DEG to 100 DEG C. yield the D 3,5-3-unsubstituted compounds. The pregnane derivatives of formulae are prepared by similar processes from 5,10-seco - 5,19 - cyclo - 10b - fluoro - D 4 - pregnene-3,20-dione, the 3,20-diols obtained in the reduction with lithium aluminium hydride being subsequently re-oxidized in the 20-position. The 17,21-dihydroxy-pregnane derivatives of formulae are prepared similarly from 21-monoesters of 5,10 - seco - 5,19 - cyclo - 10b - fluoro - D 4-pregnene - 17a ,21 - diol - 3,20 - dione which may be 11-substituted. Here, the side chain may also be protected as a 7,20:20,21-bismethylenedioxy group and 11b -ol products may be oxidized to the 11-ones. Elimination of the 21-hydroxy group from these products by conversion to the 21-tosylates and subsequent refluxing with sodium iodide in acetic acid gives products of the formulae All the free ols so produced may be esterified by standard procedures, a list of esterifying acids being provided. Examples are given. 5,10 - Seco - 5,19 - cyclo - 10b - fluoro - D 4 -pregnene - 11b ,17a ,21 - triol - 3,20 - dione 21- acetate is prepared by oxidizing 17,20:20,21-bismethylendioxy - 5,10 - seco - 5,19 - cyclo-10b - fluoro - D 4 - pregnene - 3b ,11b - diol to the corresponding 3-one, hydrolysing this to the free 11b ,17a ,21-triol-3,20-dione, and acetylating this.