Patent GB-1046242-A (GB)
Title: Steroid compounds and the preparation thereof
Inventor: BARTON DEREK HAROLD RICHARD
IPC: C07J1/00
Filed: 1961-12-05
Abstract: The invention comprises steroids having at the A and B rings the partial general formulaae <FORM:1046242/C2/1> <FORM:1046242/C2/2> <FORM:1046242/C2/3> <FORM:1046242/C2/4> wherein B represents an acyloxy group or a protected keto group such as ketal or thiketal group, and X represents a substituent capable of being eliminated as a compound of the formula HX with the 4b -hydrogen atom (X may represent a halogen atom, a hydroxy group or a sulphonyloxy group) and a process for the preparation of 4,5 - dehydro - 3 - oxo - 19 - nor-steroids by reducing the lactones of 4,5-dehydro - 10 - carboxy - 6b  - hydroxy - 3 - oxo-valency with a dissolving metal or a low-valency metal ion reducing system whereby the substitution at the 6- and 10-positions is removed but the 4,5-dehydro-3-oxo grouping is not reduced.  The dissolving metal reducing system may be zinc or copper-zinc couple in the presence of acid, or tin in the presence of acid, or aluminium amalgam in an aqueous medium.  The low-valency metal ion reducing system is defined as a compound furnishing metal ions in a low valency state which is capable of being easily oxidized to a higher valency state, for example a titanous, chromous or stannous salt such as a chloride.  The steroid lactone starting compound may be further substituted, for example by at least one substituent selected from the group consisting of a 6-methyl group, an 11-ketogroup, a 9a -halogen atom, a 16-methyl group, and a 17-hydroxy, -acetyl and -1,5-dimethyl-hexyl group. The above process may be modified in that the lactone of 4,5 - dehydro - 3 - oxo - 19 - -nor steroid may be commenced at any stage in the following synthesis which includes the preparation of the steroids of the above general formulae, a 3-R-D 4-steroid wherein R is an acyloxy group or a protected keto group is reacted with a hypohalous acid, the resulting 3 - R - 5a  - halo - 6b  - hydroxy - steroid is treated with a nitrosylating agent, the resulting 3-R-5a -halo-6b -nitrite ester is subjected to photolysis and the resulting dimeric nitroso derivative is isomerized under prototropic conditions to form an oxime of the partial formula <FORM:1046242/C2/5> wherein R has the above significance and X is a halogen, this compoun is treated with a reagent to convert an aldoxime group to an aldehyde group to form a hemiacetal of the first partial formula above, this compound is oxidized with a reagent which will oxidize a secondary alcohol to a ketone to form a lactone of the second partial formula above, the R group in the lactone is converted to a keto group, for example by hydrolysis of the acyloxy group to a hydroxy group which is then oxidized to keto or by hydrolysis of the protected keto group to a keto group, to form a lactone of the third partial formula above, and a compound of the formula HX is eliminated from the latter lactone, for example by a mineral acid catalysed reaction when X represents a halogen atom or a sulphonyloxy group, or by a dehydrating agent such as phosphorus oxy-chloride or by the application of heat when X represents a hydroxy group, to form a lactone of the fourth partial formula above.