Mibolerone

Mibolerone

Systematic (IUPAC) name
(7α,17β)-17-hydroxy-7,17-dimethylestr-4-en-3-one
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status	Schedule 3 (US)
Routes of administration	Oral
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	2-4 hours
Identifiers
CAS Number	3704-09-4 N
ATC code	none
PubChem	CID: 251636
IUPHAR/BPS	2859
ChemSpider	220460 Y
UNII	9OGY4BOR8D Y
KEGG	D05025 Y
ChEBI	CHEBI:34849 N
ChEMBL	CHEMBL425863 Y
Synonyms	(7R,8R,9S,10R,13S,14S,17S)-17-Hydroxy-7,13,17-trimethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
Chemical data
Formula	C20H30O2
Molecular mass	302.4558 g/mol
SMILES O=C4\C=C3/[C@@H]([C@H]2CC[C@]1([C@@H](CC[C@@]1(O)C)[C@@H]2[C@H](C)C3)C)CC4
InChI InChI=1S/C20H30O2/c1-12-10-13-11-14(21)4-5-15(13)16-6-8-19(2)17(18(12)16)7-9-20(19,3)22/h11-12,15-18,22H,4-10H2,1-3H3/t12-,15+,16-,17+,18-,19+,20+/m1/s1 Y Key:PTQMMNYJKCSPET-OMHQDGTGSA-N Y
NY (what is this?)  (verify)

Mibolerone is a potent anabolic steroid which is both higher affinity and more selective for the androgen receptor than metribolone.

Under the brand name "Cheque Drops", Mibolerone was marketed as a veterinary drug by the Upjohn company. It was indicated as an oral treatment for estrous (heat) prevention in adult female dogs.

Synthesis

Nandrolone (1) appears to be used to make Mibolerone. For comparison, also see bolasterone and calusterone. The first step involves extending the conjugation of the enone function by an additional double bond. Chloranil (tetrachloroquinone) is the forerunner of dichlorodicyanoquinone (DDQ), a reagent used extensively for introducing additional unsaturation in the progestin and corticoid series.

Preparation of Mibolerone: BE 610385 ; J. C. Babcock, J. A. Campbell, U.S. Patent 3,341,557 (1962, 1967 both to Upjohn).

In the case at hand, heating acetate (1) with chloranil gives the conjugated dieneone (2), and reaction of that compound with methylmagnesium bromide in the presence of cuprous chloride leads to addition of the methyl group to position 7 at the end of the conjugated system (3). The stereochemistry of the product again illustrates the preference for additions from the backside. The alcohol at C17 is then oxidized to a ketone (4). Enamines are commonly used to activate adjacent functions; they are also not infrequently used, as in this case, as protecting groups. Thus, reaction of the intermediate with pyrrolidine gives dienamine (5). This transformation emphasizes the clear difference in reactivity between ketones at C7 and C17. A second methyl Grignard addition gives the corresponding 17α-methyl derivative. Hydrolysis of the enamine function then affords mibolerone (6).