Patent GB-927327-A (GB)
Title: New cyclosteroids and process for their manufacture
IPC: C07J75/00
Filed: 1959-06-10
Abstract: The invention comprises (1) a process for the manufacture of an 18,20-cyclosteroid, wherein an 18-unsubstituted 20-oxo-steroid is irradiated with ultra-violet light in an organic solvent in the presence or absence of sulphuric acid, and a resulting 18-unsubstituted 18,20-cyclosteroid containing a 20-hydroxyl group or a D 18,20- or D 20-double bond is isolated from the reaction mixture, and, if desired, a 20-hydroxy-18,20-cyclosteroid so obtained is dehydrated to form a D 18,20- and/or D 20-18,20-cyclosteroid; and (2) as new compounds, 18-unsubstituted 20-hydroxy-18,20-cyclosteroids of the pregnane and 21-norpregnane series and esters thereof, 18-unsubstituted D 20- 18,20- cyclopregnene compounds and 18- unsubstituted D 18,20-18,20- cyclopregnene compounds. It is stated that in the presence of sulphuric acid, e.g. when the reaction medium is a mixture of acetic and sulphuric acids, dehydration on carbon atom 20 may occur.  Dehydration after the irradiation process may be effected with a halide of sulphurous acid, phosphoric acid or an organic carboxylic or sulphonic acid in the presence of, for example, an organic base; or by treatment with a mixture of bromacetamide or bromosuccinimide and then sulphur dioxide or by conversion into 20-acyloxy derivatives followed by pyrolysis; or by conversion into 20-sulphonic esters followed by reaction with lithium chloride in dimethylformamide; or by treatment with an acid silicate.  The starting materials may be of the pregnane or allopregnane series, or the corresponding 21-nor compounds, and may contain free hydroxyl or oxo groups or derivatives of these, i.e. esters, ethers, enol esters, enol ethers, acetals, corresponding thio derivatives, hydrazones, semicarbazones and oximes; fluorine or chlorine atoms; and methyl groups, for example in one or more of the positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 15, 16, 17, 19 and 21.  They may be ring saturated or contain double bonds, for example in one or several of positions 4, 5, 9(11), 11, 14 and 16.  Esters may be derived from carboxylic or sulphonic acids or from phosphoric, sulphuric or hydrohalic acids.  In examples (1) 3b -acetoxy-20-oxo-allopregnane is irradiated in hexane to give, on chromatographic separation, the corresponding 20-hydroxy-18,20-cyclo compounds; (2) the same starting material is irradiated in a mixture of acetic and sulphuric acids to give a mixture of 3b ,20-diacetoxy-18,20-cycloallopregnane and D 18,20 and D 20-3b -acetoxy-18,20-cyclo-allopregnenes, which on refluxing with acetic anhydride and pyridine gives a mixture of the pregnenes; (3) the product of (1) is hydrolysed to 3b ,20-dihydroxy-18,20-cyclo-allopregnane; (4) D 5-3-ethylenedioxy-20-oxo-pregnene by the method of (1) gives, inter alia, the corresponding 20-hydroxy-18,20-cyclo compound and a ketone of the formula <FORM:0927327/IV(a)/1> (5) the product of (4) on hydrolysis gives D 4-20-hydroxy- 3-oxo-18,20- cyclo-pregnene, which on acetylation gives the 20-acetate; (6) D 5-3-ethylenedioxy-20- hydroxy-11-oxo-18,20-cyclopregnene is prepared by the method of (1) and is then hydrolysed to the D 4-3-ketone; (7) D 5-3-ethylenedioxy-20-hydroxy-21-acetoxy-18, 20-cyclopregnene is prepared similarly; (8) D 5-3-ethylenedioxy- 11b ,20-dihydroxy-21-acetoxy-18, 20-cyclopregnene is prepared similarly and is then hydrolysed to the D 4-3-oxo-11b ,21- dihydroxy compound and oxidized to the 11-ketone (reference is also made to the use of the 11-acetate as starting material); (9) D 5-3-ethylenedioxy-20-hydroxy-11b -acetoxy-18, 20-cyclo-pregnene is prepared similarly; (10) the corresponding 11a -acetoxy compound is prepared similarly and is hydrolysed to the 11a -ol which on oxidation gives the product of (6); (11) 3b ,11b -diacetoxy- 20-hydroxy-18,20- cyclo-allopregnane is prepared similarly and is then reacted with lithium aluminium hydride to give the corresponding triol, which on acetylation gives the 3b -acetoxy compound; (12) the product of (1) is dehydrated with thionyl chloride and pyridine to give D 18,20-3b -acetoxy-18,20-cyclo-allopregnene and a product of the formula <FORM:0927327/IV(a)/2> (13) the product of (1) is dehydrated with phosphorus oxychloride and pyridine to give D 20-3b -acetoxy-18,20-cyclo-allopregnene, and by a similar method are also prepared D 5,20-3b -acetoxy-, D 4,20-3-oxo- and D 4,20-3-oxo-11a -hydroxy-18,20- cyclo-pregnadienes; (14) the product of (6) is dehydrated with Fuller's earth to give D 5,18(20)-3-ethylenedioxy-11-oxo-18,20-cyclo-pregnadiene which is hydrolysed to the D 4-3-ketone and reduced to the 11b -ol, which in turn can also be hydrolysed to the D 4-3-ketone; (15) the product of (4) gives, with thionyl chloride and pyridine, D 5,18(20)-3-ethylenedioxy-18,20-cyclopregnadiene (which on hydrolysis gives the D 4-3-ketone) and a product of the formula <FORM:0927327/IV(a)/3> which with sodium methylate is reconverted to the starting material; (16) the product of (7), with phosphorus oxychloride and pyridine, gives D 5,18(20)-3-ethylenedioxy-21-acetoxy-18, 20-cyclo-pregnadiene which on hydrolysis gives the D 4-3-keto-21-ol; (17) the product of (8) is treated similarly to give similar products and the ketal on reduction gives the 11b -ol, which on hydrolysis gives the D 4-3-ketone; (18) D 5,18(20)-3-ethylenedioxy-11b -acetoxy-18, 20-cyclopregnadiene is similarly prepared and then hydrolysed to the 11b -ol; and (19) D 5-3-ethylenedioxy-20-hydroxy-18,20-cyclo-21-nor-pregnene is prepared by the method of (1) and is then oxidized to D 5-3-ethylenedioxy-20-oxo-18,20-cyclo-21-nor-pregnene. list of further starting materials is also provided.  Specification 927,328 is referred to.