Patent GB-1016243-A (GB)
Title: New fused polycyclic hydrocarbon derivatives and processes for the preparation thereof
IPC: C07D307/93
Filed: 1962-10-26
Abstract: The invention comprises estrane derivatives of the general formula <FORM:1016243/C2/1> wherein R1 is a hydrogen atom or an acyl group derived from an organic carboxylic acid having 1-10 carbon atoms; and R2 and R3 together form a lactone ring -CO.O- between the 10 and 11 positions, in which case R4 is an enamine group NR5R6 (wherein R5 and R6 are alkyl groups which may be the same or different, each having from 1-4 carbon atoms, or together with the nitrogen atom form a substituted or unsubstituted nitrogen or nitrogen-and oxygen containing heterocyclic ring system) and double bonds are present between the 3(4) and 5(6) positions or R4 is the enamine group NR5R6, a hydroxy group is present at the 5 position and a double bond is present between the 3(4) positions, or R4 is the oxygen atom = O of a keto group, and a double bond is present between 4 (5) positions, or R4 is alkylenedioxy -O(CH2)nO- (wherein n is an integer 2-4) and a double bond is present between 5(6) positions; or R2 is a hydroxymethyl group and R3 is a hydroxy group, in which case R1 is only a hydrogen atom and R4 is the alkylenedioxy group -O(CH2)nO- and a double bond is present between the 5(6) positions, or R4 is the oxygen atom = O of a keto group and a double bond is present between the 4(5) positions and processes for the preparation thereof (a) wherein R1 is an acyl radical derived from an organic carboxylic acid having 1-10 carbon atoms, in which a 17b -acyloxy-11b -hydroxy-des A-estran-5-one is reacted with an alkyl formate (wherein the alkyl group has from 1-4 carbon atoms) in the presence of an alkali metal alcoholate or hydride to form the 10,11-hemiacetal of a 17b -acyloxy - 10b  - formyl - 11b  - hydroxy - des A-estran-5-one, which is reacted with an oxidizing agent to form the 10,11-lactone of a 17b -acyloxy-10b -carboxy - 11b  - hydroxy - des A - estran - 5-one, which is reacted with methyl vinyl ketone to form the 10,11-lactone of a 17b -acyloxy-10b -carboxy - 11b  - hydroxy - 4,5 - sec. - estran - 3,5 - dione, which is then reacted with a secondary amine HNR5R6 to form the 10,11-lactone of a 17b  - acyloxy - 10b  - carboxy - 3 - enamino - 11b  - hydroxy-estra-3,5-dione and the 10,11-lactone of a 17b  - acyloxy - 10b  - carboxy - 3 - enamino-5, 11b  - dihydroxy - estr - 3 - ene (b) in which a 17b  - substituted - 11b  - hydroxy - des A - estran-5-one is reacted with an alkyl carbonate (wherein the alkyl group has from 1-4 carbon atoms) in the presence of an alkali metal alcoholate or hydride to form the 10,11-lactone of a 17b -substituted 10b  - carboxy - 11b  - hydroxy - des A - estran-5-one, which is reacted with methylvinyl ketone to form the 10,11-lactone of a 17b -substituted 10b  - carboxy - 11b  - hydroxy - 4,5 - sec. - estran-3,5-dione, which is then reacted with a secondary amine HNR5R6 to form the 10,11-lactone of a 17b -substituted 10b -carboxy-3-enamino - 11b  - hydroxy - estra - 3,5 - diene and the 10,11-lactone of a 17b -substituted-10b -carboxy - 3 - enamino - 5,11b  - dihydroxy - estran-3-one.