Schering Aktiengesellschaft

Jurgen Ruppert

Rudolf Wiechert

Gerhard Sauer

Gregor Haffer

Ulrich Eder

Henry Laurent

Helmut Hauser

Hans Peter Lorenz

Novel benzopyran derivatives of the formula ##STR1## wherein R.sub.1 and R.sub.3 each are lower alkyl; n is the integer 1 or 2; --A--B-- is &gt;CH--CH.sub.2 -- or &gt;CH.dbd.CH--; X is a free, esterified or etherified hydroxy group; and Y is H or X and Y collectively are .dbd.O; and W is --(CH.sub.2).sub.3 --Z--R.sub.4, ##STR2## --(CH.sub.2).sub.3 --COOR.sub.6 or --(CH.sub.2).sub.3 CN, wherein V is halogen, Z is a ketalized carbonyl group or a free, esterified or etherified hydroxymethylene group, R.sub.4 and R.sub.5 each are lower alkyl and R.sub.6 is alkyl, aryl or aralkyl, are valuable intermediates in the synthesis of steroids.

Novel benzopyran derivatives

Benzopyran derivatives of the formula ##STR1## wherein R.sub.1 and R.sub.3 each are lower alkyl; n is the integer 1 or 2; --A--B-- is &gt;CH--CH.sub.2 - or &gt;CH=CH-; X is a free, esterified or etherified hydroxy group; and Y is H or X and Y collectively are =O; and W is --(CH.sub.2).sub.3 --Z--R.sub.4 ##STR2## --(CH.sub.2).sub.3 --COOR.sub.6 or --(CH.sub.2).sub.3 CN, wherein V is halogen, Z is a ketalized carbonyl group or a free, esterified or etherified hydroxymethylene group; R.sub.4 and R.sub.5 each are lower alkyl and R.sub.6 is alkyl, aryl or aralkyl, are valuable intermediates in the synthesis of steroids.

Benzopyran derivatives

Bicycloalkanes useful as intermediates in the total synthesis of steroids of the formula ##STR1## WHEREIN N IS THE INTEGER 1 OR 2; R.sub.1 is lower-alkyl; X is free or ketalized carbonyl or free, esterified or etherified hydroxymethylene; and Y is --SO.sub.2 --R.sub.2 or --C(Z)(R.sub.3)--R.sub.4 wherein R.sub.2 is alkyl, aryl or aralkyl R.sub.3 is H or lower-alkyl, R.sub.4 is alkoxycarbonyl or acyl and Z is lower-alkoxycarbonyl, lower acyl, lower alkylsulfinyl or lower-alkylsulfonyl, are produced by the steps of hydrogenating a compound of the formula ##STR2## AND CONDENSING THE THUS-PRODUCED RING SATURATED COMPOUND WITH A SALT OF THE FORMULA C(Z)(R.sub.3)R.sub.4 .sup.-Me.sup.+ wherein n, X, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Z have the values given above.

Process for the preparation of bicycloalkane derivatives

9,10-Secoestranes, useful as intermediates in the total synthesis of steroids, of the formula ##STR1## WHEREIN N IS 1 OR 2, R.sub.1 is lower alkyl, R.sub.2, R.sub.3 and R.sub.4 are hydrogen, alkoxy or acyloxy, X is free or ketalized carbonyl or free, esterified or etherified hydroxymethylene, and Y is carbonyl or dialkoxymethylene are produced by condensing, in the presence of a basic catalyst, ##STR2## WHEREIN X, n, R.sub.1, R.sub.2, R.sub.3, R.sub.4 have the values given above, and Z is Cl, Br or I, to produce a 9,10-secoestrane of the above formula wherein Y is a free carbonyl group, which can then, if desired, be ketalized to a corresponding compound wherein Y is dialkoxymethylene or like ketal group.

9,10-Secoestrane derivatives and their production

Bicycloalkane derivatives of the formula ##STR1## WHEREIN N IS 1 OR 2, R.sub.1 is lower alkyl, X is free or ketalized carbonyl or a free, esterified, or etherified hydroxymethylene, and Y is --S--R.sub.2, --SO.sub.m --R.sub.2, or ##STR2## wherein m is 1 or 2, R.sub.2 is alkyl, aryl, or aralkyl, R.sub.3 is hydrogen or lower alkyl, R.sub.4 is alkoxycarbonyl, or acyl or phenyl optionally substituted with lower alkoxy or benzyloxy- or acyloxy; and Z is nitrile, nitro, lower alkoxycarbonyl, lower alkanoyl, lower alkylsulfinyl, or lower alkylsulfonyl are useful intermediates in the total synthesis of steroids. The compounds are prepared by reacting a corresponding compound lacking the CH.sub.2 Y substituent with formaldehyde and a mercaptan or a sulfinic acid, followed if desired by oxidation and optional salt condensation.

Bicycloalkanes

9,10-Secoestranes, useful as intermediates in the total synthesis of steroids, of the formula ##STR1## wherein n is 1 or 2, R.sub.1 is lower alkyl, R.sub.2, R.sub.3 and R.sub.4 are hydrogen, alkoxy or acyloxy, X is free or ketalized carbonyl or free, esterified or etherified hydroxymethylene, and Y is carbonyl or dialkoxymethylene are produced by condensing, in the presence of a basic catalyst, ##STR2## WHEREIN X, n, R.sub.1, R.sub.2, R.sub.3, R.sub.4 have the values given above, and Z is Cl, Br or I, to produce a 9,10-secoestrane of the above formula wherein Y is a free carbonyl group, which can then, if desired, be ketalized to a corresponding compound wherein Y is dialkoxymethylene or like ketal group.

6,9-Oxido-9,10-seco-1,3,5(10),6,8,14-estrahexaenes, useful as intermediates in the total synthesis of steroids, of the formula ##SPC1## Wherein n is 1 or 2, R.sub.1 is lower-alkyl, R.sub.2, R.sub. 3 and R.sub.4 are H, alkoxy or acyloxy, X is a free or ketalized keto or free, esterified or etherified hydroxymethylene, are produced by the cyclization, with an acid catalyst, of a 9,10-secoestrane of the formula ##SPC2## Wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X and n have the values given above, and Q is carbonyl or dialkoxymethylene. Hydrogenation produces the corresponding 6,9-oxido-9,10-seco-1,3,5(10)-estratrienes and 9-oxy-9,10-seco-1,3,5(10)-estratrienes.

Process for the preparation of 9,10-secoestrane derivatives

6,9-Oxido-9,10-seco-1,3,5(10),6,8,14-estrahexaenes, useful as intermediates in the total synthesis of steroids, of the formula ##SPC1## Wherein n is 1 or 2, R.sub.1 is lower-alkyl, R.sub.2, R.sub.3 and R.sub.4 are H, alkoxy or acyloxy, X is a free or ketalized keto or free, esterified or etherified hydroxymethylene, are produced by the cyclization, with an acid catalyst, of a 9,10-secoestrane of the formula ##SPC2## Wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X and n have the values given above and Q is carbonyl or dialkoxymethylene. Hydrogenation produces the corresponding 6,9-oxido-9,10-seco-1,3,5(10)-estratrienes and 9-oxy-9,10-seco-1,3,5(10)-estratrienes.

6,9-Oxido-9,10-secoestrane derivatives and method of synthesis

Novel benzopyran derivatives of the formula ##SPC1## Wherein R.sub.1 and R.sub.3 each are lower alkyl; n is the integer 1 or 2; --A--B-- is &gt;CH--CH.sub.2 -- or &gt;CH=CH--; X is a free, esterified or etherified hydroxy group; and Y is H or X and Y collectively are =O; and W is --(CH.sub.2).sub.3 --Z--R.sub.4, --(ch.sub.2).sub.3 --coor.sub.6 or --(CH.sub.2).sub.3 CN, wherein V is halogen, Z is a ketalized carbonyl group R.sub.4 and R.sub.5 each are lower alkyl and R.sub.6 is alkyl, aryl or aralkyl, are valuable intermediates in the synthesis of steroids.

Process for preparing benzopyran derivatives

20-Cyano-17.alpha.-H steroids having as the 17-position substituent the group ##EQU1## wherein R is H, alkyl of 1-8 carbon atoms or benzyl, having a 13-methyl or 13-ethyl group and which are unsubstituted or substituted with an .alpha.-methyl group in the 16-position are converted to the corresponding 20-keto steroids by reaction in an aprotic solvent with a deprotonating agent containing an alkali metal, an alkaline earth metal, copper(I) or thallium(I), and optionally additionally with a copper(I) salt or a thallium(I) salt or a silver(I) salt, and thereafter conducting an oxidative splitting reaction with oxygen. The thus-produced 17.beta.-oxalyl steroids possess pharmacological activity, e.g., anti-inflammatory activity, or are useful as intermediates for the production of pharmacologically active steroids.

Growing community of inventors

Berlin, Germany

Jurgen Ruppert