Patent GB-1079372-A (GB)
Title: Steroidal lactones
Inventor: JUNG CHRISTOPHER JOSEPH
IPC: C07J73/00
Filed: 1965-02-08
Abstract: Novel compounds of the formula <FORM:1079372/C2/1> (wherein the D 4 or D 5(10) double bond is optional; R is H or methyl; R1 is H or C1- 6 alkanoyl; R11 is C2- 6 alkenyl, or, when there is a D 5(10) double bond, can also be C2- 6 alkynyl; and the ring A saturated compounds contain 5a -H) are prepared (1) by cleaving compounds of the formula <FORM:1079372/C2/2> (where Z is carbonyl, b -hydroxymethylene or b -alkanoyloxymethylene) to give compounds of the formula <FORM:1079372/C2/3> contacting these with a reducing agent to give compounds of the formula <FORM:1079372/C2/4> (where X is b -hydroxymethylene or b -alkanoyl-oxymethylene) hydrolysing if necessary to the 17b -ols, oxidizing to the 17-ones, converting to compounds of the formula <FORM:1079372/C2/5> (where M is an alkali metal, alkaline earth metal, magnesium or ammonium cation) and reacting these with alkynylating or alkenylating agents followed by acidification when the A ring is saturated and reduction of alkynyl compounds to alkenyl compounds; (2) by dehydrogenating 17a  - alkynyl - testosterones to give D 1 - 17a -alkynyl -testosterones hydroxylating these to the 1,2-diols, cleaving these to give 1,2-seco-A-nor-17a  - alkynyl - 17b  - hydroxy - 5a  - androst - 3 - en-2-oic acids, reducing these to the 4,5-dehydrolactones in which the alkynyl group is then hydrogenated; (3) by dehydrogenating compounds of the formula <FORM:1079372/C2/6> to the corresponding 1,4-dienes, hydroxylating, cleaving the resulting 1,2-diols to give 6b ,19-epoxy - 1 - oxo - 1,2 - seco - A - nor - androst - 3-en-2-oic acids, reducing, acidifying and heating to give 6b ,19-epoxy-17b -hydroxy-2-oxa-androst-4-en-3-one, oxidizing and cleaving to give 19-hydroxy - 2 - oxo - androst - 4 and 5 - ene - 3,17-diones oxidizing to the 10b -carboxy compounds, heating with pyridine to give 2-oxaestra-5(10)-ene-3,17-dione, reducing to the diol, methylating to the 3-methyl ether, oxidizing to the 17-one, alkylating or alkynenylating, converting the 3-ether to the 3-ol and oxidizing, and, if desired, isomerizing the D 5(10) to the D 4 derivatives via the 1,2 - seco - 1 - hydroxy - A - nor - estra - 3-en-2-oic acids; and (4) by converting 2-oxaestra-5(10)-ene-3,17-dione to a compound of the formula <FORM:1079372/C2/7> reacting with an alkynylating or alkenylating agent and acidifying.  The D 5(10) compounds of the invention are isomerized to the D 4 compounds with an aqueous organic base. Acylation of the 17-ols gives the 17-acylates, and reduction of the 17-alkynyl compounds gives the 17-alkenyl compounds.  The 17-alkenyl estrenes may also be prepared by reaction of the 17a -alkynyl-6b ,19-epoxy compounds with zinc to give 17b ,19-dihydroxy-2-oxa-17a -alkenyl-androst-4-en-3 -ones, oxidizing to the 10b -carboxy compounds and decarboxylating.  6b ,19 - epoxy - 17a  - ethynyl - 17b - hydroxy - 2 - oxa-androst -4-en-3-one is prepared by converting 6b ,19-epoxy-2-oxa-androst-4-ene-3,17-dione to 6b ,19 - epoxy - 1 - hydroxy - 17 - oxo - 1,2 - seco-A-norandrost -3-en-2-oic acid and ethynylating and acidifying this.