<unk> , also known as 17α-ethynyl-19-nortestosterone or as 17α-ethynylestra-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone. It is specifically a derivative of testosterone in which an ethynyl group has been added at the C17α position and the methyl group at the C19 position has been removed; hence, it is a combined derivative of ethisterone (17α-ethynyltestosterone) and nandrolone (19-nortestosterone). These modifications result in increased progestogenic activity and oral bioavailability as well as decreased androgenic/anabolic activity. Derivatives<unk>  <unk>  is the parent compound of a large group of progestins that includes most of the progestins known as the 19-nortestosterone derivatives. This group is divided by chemical structure into the estranes (derivatives of<unk>  and the gonanes (18-methylgonanes or 13β-ethylestranes; derivatives of levonorgestrel) and includes the following marketed medications: ; Estranes * Etynodiol diacetate (3β-hydroxy-NET 3β,17β-diacetate) * Lynestrenol (3-desoxy-NET) *<unk>  acetate <unk>  17β-acetate) *<unk>  enanthate (17β-enanthate) * Noretynodrel (δ5(10)-NET) * Norgestrienone (δ9,11-NET) * Quingestanol acetate <unk>  17β-acetate 3-cyclopentyl enol ether) * Tibolone (7α-methyl-δ5(10)-NET) ; Gonanes * Desogestrel (3-deketo-11-methylene-18-methyl-NET) * Etonogestrel (11-methylene-18-methyl-NET) * Gestodene (18-methyl-δ15-NET) * Gestrinone (18-methyl-δ9,11-NET) * Levonorgestrel (18-methyl-NET) * Norelgestromin (18-methyl-NET 3-oxime) * Norgestimate (18-methyl-NET 3-oxime 17β-acetate) * Norgestrel (13-ethyl-NET) Several of these act as prodrugs of<unk> , including<unk> A,<unk> E, etynodiol diacetate, lynestrenol, and quingestanol acetate. Noretynodrel may also be a prodrug of<unk> .<unk> A is taken by mouth similarly to<unk> , while<unk> E is given by injection into muscle. Non-17α-ethynylated 19-Nortestosterone (19-NT) progestins which are technically not derivatives of<unk>  (as they do not have a C17α ethynyl group) but are still closely related (with other substitutions at the C17α and/or C16β positions) include the following marketed medications: * The C17α vinyl (ethenyl) derivatives norgesterone (17α-vinyl-δ5(10)-19-NT) and norvinisterone (17α-vinyl-19-NT) * The C17α allyl derivatives allylestrenol (3-deketo-17α-allyl-19-NT) and altrenogest (17α-allyl-δ9,11-19-NT) * The C17α alkyl derivative normethandrone (17α-methyl-19-NT) * The C17α cyanomethyl derivative dienogest (17α-cyanomethyl-δ9-19-NT) * The C16β ethyl derivative oxendolone (16β-ethyl-19-NT) Many anabolic steroids of the 19-nortestosterone family, like norethandrolone and ethylestrenol, are also potent progestogens, but were never marketed as such. Synthesis Chemical syntheses of<unk>  have been published. Synthesis 1 Searle & Co). Estradiol 3-methyl ether (1, EME) is partially reduced to the 1,5-diene (2) as also occurs for the first step in the synthesis of nandrolone. Oppenauer oxidation then transforms the C17β hydroxyl group into a ketone functionality (3). This is then reacted with metal acetylide into the corresponding C17α ethynyl compound (4). Hydrolysis of the enol ether under mild conditions leads directly to (5), which appears to be noretynodrel (although Lednicer states that it is "etynodrel" in his book (which may be a synonym etynodiol); etynodrel is with a chlorine atom attached), an orally active progestin. This is the progestogen component of the first oral contraceptive to be offered for sale (i.e., Enovid). Treatment of the ethynyl enol ether with strong acid leads to<unk>  (6). In practice, these and all other combined oral contraceptives are mixtures of 1 to 2% EE or mestranol and an oral progestin. It has been speculated that the discovery of the necessity of estrogen in addition to progestin for contraceptive efficacy is due to the presence of a small amount of unreduced EME (1) in early batches of 2. This when subjected to oxidation and ethynylation, would of course lead to mestranol (3). In any event, the need for the presence of estrogen in the mixture is now well established experimentally. Synthesis 2<unk>  synthesis #2.<unk>  is made from estr-4-ene-3,17-dione (bolandione), which in turn is synthesized by partial reduction of the aromatic region of the 3-O-methyl ether of estrone with lithium in liquid ammonia, and simultaneously of the keto group at C17α to a hydroxyl group, which is then oxidized back to a keto group by chromium trioxide in acetic acid. The conjugated C4-C5 olefin and the carbonyl group at C3 is then transformed to dienol ethyl ether using ethyl orthoformate. The obtained product is ethynylated by acetylene in the presence of potassium tert-butoxide. After hydrochloride hydrolysis of the formed O-potassium derivative, during which the enol ether is also hydrolyzed, and the remaining double bond is shifted, the desired<unk>  is obtained.
Norethisterone
Cloxotestosterone acetate
Androstanolone benzoate
Norvinisterone
Norethandrolone
Oxandrolone
Nandrolone propionate
Ethisterone