Patent GB-967005-A (GB)
Title: Steroids
IPC: C07J75/00
Filed: 1962-01-31
Abstract: The invention comprises steroids of the general formulae <FORM:0967005/C1/1> <FORM:0967005/C1/2> wherein B represents the cis or trans form of <FORM:0967005/C1/3> or <FORM:0967005/C1/4> Z represents <FORM:0967005/C1/5> and R11 represents an alkyl group containing 1 to 8 carbon atoms; a process which comprises (a) dialkylating a 5a , 6a -oxido -16- pregnen-3b -ol -20- one 3-acylate with a Grignard alkylating agent in which the alkyl group has 1 to 8 carbon atoms and acylating the resulting 6b , 16a -dialkyl-17 (20)-pregnen-3b , 5a , 20-triol to form the corresponding triacylate; (b) epoxidising said triacylate with a peracid to form a 17a , 20-oxido-6b , 16a -dialkylpregnen-3b , 5a , 20-triol 3b , 5a , 20-triacylate; (c) hydrolysing said triacylate under alkaline conditions to form a 6b , 16a -dialkylpregnan-3b , 5a , 17a -triol -20- one 5-monoacylate (the 5-monoacylate may be purified by acylating to form the corresponding 3b , 5a -diacylate and selectively hydrolysing back to the 5-monoacylate); and (d) oxidising the 3b -hydroxy group of said monoacylate to form 6b , 16a -dialkylpregnan-5a , 17a -diol-3, 20-dione 5-acylate; a process for the preparation of steroids of the general formula <FORM:0967005/C1/6> wherein B and R11 have the above significance by reacting steroids of the general formula <FORM:0967005/C1/7> with an alkyl Grignard reagent to produce an intermediate dialkylated Grignard complex which reacting this complex without isolation with an acylating agent and thereafter, where it is desired to obtain the 17(20)-oxido compound, reacting the resulting 17(20)-enol acylate with a peracid; and a process for the preparation of steroids of the general formula <FORM:0967005/C1/8> wherein Z and R11 have the above significance, by hydrolysing 17a , 20-oxido-6b , 16a -dialkyl-pregnan-3b , 5a , 20-triol 3b , 5a , 20-triacylate with an alkali to form 6b , 16a -dialkylpregnan-3b , 5a , 17a -triol -20- one 5-acylate, thereafter if desired, oxidising the 3b -hydroxy group to a 3-keto group or acylating the 3b -hydroxy group to form a 3b -acyloxy group.  6a , 16a -Dialkyl -17a - hydroxy-progesterone and the 17a -acylate thereof are prepared by treating 6b , 16a -dialkyl-pregnan-5a , 17a -diol-3, 20-dione 5-acylate with alkali to form the free 17a -hydroxy compound and, when required, acylating the 17a -hydroxy group to form the 17a -acylate.  D 6-Dehydro- and D 1,6-bisdehydro-derivatives of 6a , 16a -dialkyl -17a - progesterone and the 17a -acylates thereof are prepared by the following methods: (a) by dehydrogenating 6a , 16a -dialkyl -17a - hydroxy-progesterone and 17a -acylates thereof with chloranil in refluxing t-butanol to form the D 6-dehydro derivatives and in refluxing sec-amyl alcohol to form the D 1,6-bisdehydro derivatives; (b) by dehydrogenating the above mentioned D 6-dehydro derivatives with chloranil in refluxing sec.-amyl alcohol to form the D 1, 6-bisdehydro derivatives; (c) by acylating the corresponding free 17a -hydroxy compounds; (d) by dehydrogenating the required D 1-dehydro compounds with chloranil in secamyl alcohol to form the D 1, 6-derivatives, and (e) by dehydrogenating the required D 6-dehydro compounds with 2,3-dichloro-5, 6-dicyano-benzoquinone.  D 1-Dehydro-derivatives of 6a , 16a -dialkyl-17a -progesterone and the 17a -acylates thereof are prepared by dehydrogenating 6a , 16a -dialkyl-17a -hydroxy-progesterone and 17a -acylates thereof with chloranil in refluxing sec-amyl alcohol (under these conditions a D 6-double bond may also be introduced) or with selenium dioxide, 2,3-dichloro-5, 6-dicyanobenzoquinone or dehydrogenating microorganisms such as Bacillus sphaericus and Corynebacterium simplex, and by acylating the required 17a -hydroxy compounds.  Specification 938,445 is referred to.