Hoffmann-la Roche Inc.

Werner Meier

Andor Furst

Ludwig Labler

Jean-Marie Cassal

John William Scott

Harald Weiser

Hermann Zucker

Paul Buchschacher

Walter A Rambeck

Novel combination preparations containing 1.alpha.,25-dihydroxy vitamin D.sub.3 or 1.alpha.-hydroxy vitamin D.sub.3 and 1.alpha.,24,25(or 1.alpha.,25,26)-trihydroxy vitamin D.sub.3 are described. These preparations are useful in the treatment of various disorders which are characterized by disturbances of the calcium and phosphate metabolism such as osteoporosis and can also be used in animal nutrition.

Composition which contain hydroxylated derivatives of vitamin D.sub.3

The invention is concerned with a process for the preparation of 1 hydrogen or hydroxy cholesterol derivatives and intermediates therefor. The compounds of the present invention are useful as intermediates in the preparation of 24,25-dihydroxy and 1.alpha.,24,25-trihydroxycholecalciferol.

Process for the preparation of cholesterol derivatives and novel

The invention is concerned with a process for the preparation of 1 hydrogen or hydroxy cholesterol derivatives and intermediates therefor. The compounds of the present invention are useful as intermediates in the preparation of 24,25-dihydroxy and 1.alpha., 24,25-trihydroxycholecalciferol.

The present disclosure is directed to a process for the preparation of cholesterol derivatives from corresponding 21-hydroxymethyl steroidal compounds.

Process for the manufacture of cholesterol derivatives

A process for the synthesis of 1.alpha.,3.beta.-dihydroxy-.DELTA..sup.5 -steroids from steroids such as 1.alpha.,2.alpha.-epoxy-cholesta-4,6-dien-3-one, which is reacted with lithium in liquid ammonia in the absence of a proton donator and subsequently reduced by repeated alternative additions of a proton donator, said additions being followed in each case by an equivalent amount of lithium. The final product, a 1.alpha.,3.beta.-dihydorxy-.DELTA..sup.5 -steroid, is useful in the synthesis of derivatives of cholecalciferol.

Process for 1.alpha.,3.beta.-dihydroxy-.DELTA..sup.5 -steroids

The present invention relates to pregnane derivatives of the formula ##STR1## wherein R.sup.1 and R.sup.3 are hydroxyl groups or readily cleavable etherified or esterified hydroxyl groups and R.sup.20 is hydroxymethyl or readily cleavable etherified or esterified hydroxy methyl, formyl, carboxyl or carbalkoxy useful as intermediates for the preparation of 1.alpha.-hydroxycholecalciferols. The present invention also relates to processes for the preparation of the pregnane derivatives and the intermediates thereof.

Pregnane derivatives

Treatment of de-A steroids with a methylation agent at extremely low temperatures, i.e., below -50.degree. C. produces corresponding 10.beta.-methyl-.DELTA..sup.9(11) -deA steroids with a high 10.beta. to 10.alpha. isomer ratio. A number of the product 10.beta.-methyl-.DELTA..sup.9(11) -deA steroids are novel compounds. They are useful as intermediates in the synthesis of known medicinally valuable steroids.

Methylation of de-A steroids

A process for the preparation of 9,10-seco-steroids of the formula ##STR1## WHEREIN R.sup.1 and R.sup.2 independently are hydrogen, amino, OR.sup.5, OCOR.sup.6 or NHCOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl or phenyl; R.sup.3 is lower alkyl; R.sup.4 is oxo, ##STR2## wherein R.sup.13 is lower alkyl, lower alkoxy -- lower alkylene, tetrahydropyranyl or tetrahydrofuryl, R.sup.14 is lower alkyl or aryl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene, and n is 1 or 2 is disclosed. The 9,10-seco-steroids of this invention are useful intermediates for the preparation of steroids.

9,10-Seco-steroids

A process for the preparation of 9,10-seco-steroids of the formula ##STR1## wherein R.sup.1 and R.sup.2 independently are hydrogen, amino, OR.sup.5, OCOR.sup.6 or NHCOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl or phenyl; R.sup.3 is lower alkyl; R.sup.4 is oxo, ##STR2## wherein R.sup.13 is lower alkyl, lower alkoxy - lower alkylene, tetrahydropyranyl or tetrahydrofuryl, R.sup.14 is lower alkyl or aryl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene, and n is 1 or 2 is disclosed. The 9,10-seco-steroids of this invention are useful intermediates for the preparation of steroids.

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Bottmingen, Switzerland

Werner Meier