Roussel Uclaf

Hoechst Marion Roussel

Other

Francis Brion

Christian Diolez

Jean Buendia

Michel Vivat

Christian Marie

Colette Colladant

Alain Mazurie

Didier Pronine

Edmond Toromanoff

Bernadette Chappert

Michel Middendorp

Jacques Lagouardat

Didier Babin

Neerja Bhatnagar

Christian Richard

Raphael Bouchet

Jacques Scholl

Novel tricyclic compounds of formula I as defined in the specification, a process for their preparation and their use for the preparation of optically active or racemic colchicine and thiocolchicine derivatives.

Tricyclic compounds

The invention relates to a novel process for preparing compounds of the formula (IV) or (I):

Method for preparing alkyloxy furanone derivatives, compounds obtained by said method and use of said compounds

A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 8 carbon atoms, R.sub.2 and R.sub.4 are alkyl of 1 to 4 carbon atoms and R.sub.3 is alkyl of 1 to 8 carbon atoms comprising reacting a compound of the formula ##STR2## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined as above or an amine salt thereof with an electrophilic halogenating agent to obtain a compound of the formula ##STR3## wherein Hal.sub.1 is halogen, reacting the latter with a halohydroxylating agent to obtain a compound of the formula ##STR4## wherein Hal.sub.2 is halogen, reacting the latter with a base to obtain a compound of the formula ##STR5## reacting the latter with a diastereoselective reducing agent to obtain a compound of the formula ##STR6## reacting the latter with a reducing agent to obtain a cis racemic compound of formula I and optionally resolving the latter with a resolution agent to obtain the desired optical form and novel intermediates.

Preparation of 4-phenyl-1,2,3,6-tetrahydropyridines

A process for the production of a compound of the formula ##STR1## wherein R.sub.1 is acyl of 1 to 8 carbon atoms,. The compound is formed by the reduction of an intermediary to form an alcohol, epoxidation and hydrolyzation of the alcohol to form a compound of formula ##STR2## followed by the acylation of the hydroxy functions and the elimination of the 17.alpha.-substituent.

Process for the production of 21-acyloxy-4,9

The novel intermediates of the formula ##STR1## wherein L, K and M are as defined in the specification which are useful intermediates for the preparation of .DELTA..sup.4,9(11),16 -pregnatriene-3-ones.

Intermediates for the preparation of .DELTA..sup.4,9(11),17(20)

A compound having a formula ##STR1## in which K is defined as above, C--P being CH.sub.2 or --C.dbd.CH.sub.2 or ##STR2## and J is --SO.sub.2 R.sub.2, or C--P is C.dbd.O and J is --CH.sub.2 Hal.sub.2, or C--P is --CH SO.sub.2 R.sub.2 and J is CO.sub.2 R or Hal.sub.1, R.sub.2 is methyl, phenyl, tolyl or xylyl, R is alkyl of 1 to 6 carbon atoms, aralkyl of 7 to 15 is carbon atoms or a silylated remainder selected from the group consisting of trimethylsilyl, tert.-butyldimethylsilyl, triphenylsilyl and diphenyltert.-butylsilyl, Hal.sub.1 is halogen, Hal.sub.2 is chlorine, bromine or iodine and the wavy lines symbolize any one of the isomer forms or their mixtures which are intermediates.

A process for the preparation of a compound of the formula ##STR1## wherein R and R' and the A and B are as defined in the specification. ##STR2## K is selected from the group consisting of ##STR3## n is 2 or 3 and the dotted lined is an optional bond.

Preparation of 11-keto steroids

A compound of the formula ##STR1## wherein K is a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3 and L is a 11.beta.-hydroxy, the dotted line in the 11-position is not a bond and X is chlorine, bromine or iodine which avoids an 11-hydroxylation step in the preparation of hydrocortisone.

Process for the preparation of hydrocortisone

A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is acyl of an organic carboxylic acid of 1 to 8 carbon atoms useful as intermediates for synthesis of therapeutically active steroids.

Process for preparation of .DELTA..sup.4,9(11),16

A compound of the formula ##STR1## wherein K represents a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3, and M is chlorine, bromine, or ##STR3## wherein R.sub.a and R.sub.b are individually selected from the group consisting of hydrogen, --OH, and alkyl and alkoxy of 1 to 4 carbon atoms and R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, aralkyl of 7 to 15 carbon atoms, trialkyl silyl triphenyl silyl and diphenyl alkyl silyl.

Novel compounds of the formula ##STR1## wherein either K' is oxygen or a K, a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3, the 17-position dotted line is a bond, R.sub.a and R.sub.b are individually selected from the group consisting of hydrogen, hydroxy, alkyl and alkoxy of 1 to 4 carbon atoms or K' is an oxygen, the 17-position dotted line is an epoxy and R.sub.a and R.sub.b have the meaning indicated above which are useful intermediates for the preparation of hydrocortisone.

Intermediate steroid compounds

A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is acyl of 1 to 8 carbon atoms, by reducing an intermediary to form an alcohol, oxidizing the alcohol to form an aidehyde, which is subjected to the action of an acyloxylation agent.

Process for preparing 21 acyloxy-.DELTA.4,9(11),16 pregnatrienes

A novel process for the preparation of isomers or mixtures of isomers of compounds of the formula ##STR1## and novel intermediates therefore.

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Gagny, France

Francis Brion