Patent GB-989881-A (GB)
Title: Improvements in or relating to 10 -methyl steroids and the production thereof
IPC: C07J5/00
Filed: 1961-05-26
Abstract: The invention comprises 9b ,10a -methyl-steroids of the general formula <FORM:0989881/C2/1> wherein all the symbols R1 to R9 must comply with the ultra-violet light absorption requirements detailed below and with the steric hindrance requirements detailed below, and subject to these requirements, R1 represents a hydrogen atom or an alkyl group containing from 1 to 6 carbon atoms, R2 represents 0, 1 or more double bonds between carbon atoms 2 and 3, 15 and 16 or 16 and 17, n denotes 0, 1 or 2, R3 represents hydrogen or an alkyl group containing from 1 to 6 carbon atoms, a hydroxy group which may be etherified or esterified or a keto group, R4 represents hydrogen, a hydroxy group which may be etherified or esterified, or a keto group which may be ketalized, R5 represents hydrogen, chlorine or fluorine or one or two alkyl groups containing from 1 to 6 carbon atoms, R6 represents hydrogen or a hydroxy group which may be etherified or esterified or a keto group which may be ketalized, R7 represents hydrogen or an alkyl group containing 1 to 6 carbon atoms and which may contain double or triple bonds or hydroxy groups which may be etherified or esterified and/or a keto group which may be ketalized, R8 represents a hydrogen atom or a hydroxy group which may be etherified or esterified, provided that both of the groups R7 and R8 are not hydrogen atoms, and R9 represents hydrogen or a hydroxy group which may be etherified or esterified or an alkyl group containing from 1 to 6 carbon atoms or together with R7 or R8 represents an epoxy oxygen atom, and the preparation thereof by irradiating the corresponding 9a ,10b -methyl-steroids in a dissolved or dispersed condition, firstly by short-wave ultra-violet light and subsequently by long-wave ultra-violet light.  The steroid reaction must also have an ultra-violet absorption spectrum between 220 and 330 mm  which is determined substantially only by the 5,7-dehydro system, substituents being not present which influence said absorption spectrum either by having a natural absorption between 220 and 330 mm  or by materially influencing the absorption of the 5,7-dehydro system.  Thus the presence of a keto group or one or more double bonds in conjugation with the 5,7-dehydro system must be avoided.  In addition, the starting compound must be free of any substituent providing steric hindrance of the 10-methyl group. The expressions short-wave and long-wave ultra-violet light have the following meaning:-the short-wave ultra-violet light is electromagnetic radiation of which at least part of the spectrum has a wavelength between 220 and 290 mm , the long-wave ultra-violet light is electromagnetic radiation of which at least part of the spectrum has a wavelength between 220 and 320 mm , the radiation energy of the region between 290 and 320 mm being greater than that of the wavelength region between 220 and 290 mm . During the above process a keto group such as a 3-, 11- and/or 20-keto group, must be protected, for example by thio- or hemithio-ketal formation or alkylene diketal formation.  By the above process it is possible to prepare 9b ,10a -pregna - 5,7 - diene - 3b - ol - 20 - one (may be converted to the 3-31,51-dinitrobenzoate) from pregna - 5,7 - diene - 3b  - ol - 20 - one; 9b ,10a -pregna - 5,7 - diene - 3b ,17a  - diol - 20 - one from pregna - 5,7 - diene - 3b ,17a  - diol - 20 - one (obtainable by brominating 5-pregnene-3b ,17a -diol-20-one-3-acetate to form the corresponding 7-bromo-compound, splitting of hydrobromic acid with collidine to form pregna-5,7-diene-3b ,17a  - diol - 20 - one 3 - acetate and hydrolysing the latter compound); 9b ,10a -pregna-5,7-diene - 3b  - ol - 16,17 - epoxy - 20 - one from 16,17 - epoxy - pregna - 5,7 - diene - 3b  - ol - 20 - one (obtainable by brominating pregna-5-ene-3b  - ol - 16,17 - epoxy - 20 - one 3 - acetate to form the corresponding 7-bromo compound, splitting out hydrobromic acid with collidine); 9b ,10a  - pregna - 5,7 - diene - 3b  - ol - 16 - methyl-20 - one from 16 - methyl - pregna - 5,7 - diene - 3b  - ol - 20 - one (obtainable by the method previously described); 9b ,10a  - pregna - 5,7 - diene - 3b ,16 - diol - 20 - one from pregna - 5,7 - diene - 3b ,16 - diol - 20 - one (obtainable by brominating pregna - 5 - ene - 3b ,16 - diol - 20 - one - 3,16 - diacetate to form the corresponding 7-bromo compound, splitting off hydrobromic acid with pyridine to form pregna-5,7-diene - 3b ,16 - diol - 20 - one 3,16 - diacetate and saponifying this compound; and 9b ,10a -pregna-5,7 - diene - 3,20 - dione - 11,17 - diol - 3 - ketal - 11 - acetate from pregna - 5,7 - diene - 3,20 - dione - 11,17 - diol - 3 - ketal - 11 - acetate (obtainable by ketalizing hydrocortisone 11 - acetate, brominating the resulting 3-ketal to form the corresponding 3-ketal-7-bromo-compound and dehydrobrominating this compound. Specification 929,271 is referred to.