Testosterone, acetate

Generally, methylation of enolate ions with isotopically tagged methyl iodide is a satisfactory labeling procedure. For example, application of this method has given the C-18 labeled steroids, (244) and (245) (see above), 17 -acetoxy-4jS-trideuteriomethyl-4a-methyl-l9-norandrost-5-en-3-one (264) and 19- C-testosterone acetate (268). Methylation of the anion derived from 17jS-acetoxy-4-methyl-l9-norandrost-4-en-3-one (263) with d3-methyl iodide occurs predominantly at C-4, yielding mainly the 4)S-trideuterio-methyl derivative (264) and about 10% of the corresponding C-4 epimer... 

Preparation of IQ- C-testosterone acetate has been achieved by methyla-tion of a 19-nor-seco-androstane derivative (266) with C-methyl iodide. 

A sequence of standard transformations of the oxo-steroid intermediate (267) then ultimately led to the desired product (268). In our opinion, this sequence could be applied equally well to tlie preparation of 19-d3-testosterone acetate in high isotopic purity by methylating (266) with da-methyl iodide. 

Testosterone acetate (86) is treated with DDQ in refluxing benzene. It is necessary to purify the product by a rough chromatography and by crystallization.This reaction is normally accompanied by some A -introduc-tion, even in dry benzene, which gives the most selective reaction. Pure -3-ketones are normally obtained in 55-75% yields by this route (see, for example, ref. 171). 

More recently, permaleic acid has been recommended as a very satisfactory reagent for the Baeyer-Villiger reaction. It reacts almost as fast as trifluoroperoxyacetic acid and does not require buffering. Unfortunately, neither of these two reagents has been used extensively on 20-keto steroids a patent claims the conversion of progesterone to testosterone acetate with trifluoroperoxyacetic acid, but a later communication describes the ready reaction of 3-keto-A" -steroids with this reagent. 

Photoketone (118) has served as the key intermediate in a relatively simple transformation of 3-keto-10/ -steroids to 3-keto-lOa-isomers without the assistance of other functional groups suitably situated next to the ring junction—a task that appears difficult to attempt by other methods. Optimal yields of (118) are achieved by catalytic hydrogenation of the unsaturated ketone (175), the photoisomer of 1-dehydrotestosterone acetate (see section III-C). In this way, a 6-step conversion of 1-dehydrotestosterone acetate (174) to IOa-testosterone acetate (127 acetate) is achieved in good yield. ° ... 

Irradiations of Testosterone Acetate (114), —In t-Butanol. 1.25 g of (114) in 250 ml t-butanol is irradiated for 32 hr at 30° under nitrogen with a Hanau Q81 high-pressure mercury lamp placed in a central water-cooled Pyrex immersion well with acetone filter. The solvent is evaporated in vacuo and the residue chromatographed on 125 g silica gel with benzene-ethyl acetate (4 1) to yield 0.29 g 17 -hydroxy-la,5 -cyclo-10a-androstan-2-one acetate [(118) 23%] mp 164-165°, after crystallization from acetone-hexane [a]i3 37 (CHCI3) 0.14 g cyclopentanone (120) (11%) mp 106-107° [aJo 38° (CHCI3) and 0.58 g starting material [(114) 46%]. Ratio (118) (120) - 2 1. 

Both types of processes, 7r -assisted y, -bond cleavage and P -bonding, have been invoked to operate in the phototransformations of the aldehyde-ketone (153) to products (155), (156) and (158). The conversions have been observed at room temperature in dioxane, t-butanol, ethanol and benzene using light of wavelengths 2537 A or above 3100 A or sensitization by acetophenone. The phosphorescing excited triple state of (153) is very similar to that of testosterone acetate (114), but its reactions are too rapid... 

Photochemical cyclohex-2-enoneH> bicyclo (3.1.0) hexan-2-one rearrangement irradiation of testosterone acetate, 322 Photochemical rearrangements of cross-conjugated cyclohexadienones and their photoisomers... 

Testosterone acetate, 312, 320, 322, 343 lOa-Testosterone acetate, 320 5a,6/3,17a,21-Tetrabromo-3/3-hydroxy-pregnan-20-one acetate, 160 3,ll/3,17a,21 -tetrahy droxy- 19-norpregna-l,3,5(10)-trien-20-one 11,21-diacetate 3-methyl ether, 224... 

Hydroxy-5-oxo-3,5-seco-4-norandrostane-3-carboxylic acid has been prepared by ozonolysis of testosterone2-4 or of testosterone acetate, followed by alkaline hydrolysis,5 and by the oxidation of testosterone acetate with ruthenium tetroxide.9... 

Ammonium hexanitrocerate(IV) [Ceric ammonium nitrate], 55 43 Androst-4-en-3-one, 17(3-(acetoxy)-, [Testosterone acetate], 55, 68, 69 Azide, sodium [Sodium azide] 55, 34... 

Temperature changes could also have another effect. Steroidal ketones have been demonstrated to have nearly degenerate zn-n and states, and the possibility of a thermal equilibrium between those states has been pointed out. 146> In fact, testosterone acetate and 10-methyl-A -oct alone, both very similar molecules to the reactant in Eq. 55, undergo photoreactions from two different triplet states. 144> So we ought to consider what the reactivity of the n-n state would be, and whether product distribution would differ from the two states. If so, temperature variation could change product distribution due to a change in the relative proportions of triplet states. 

The structure of this drug allowed for near immediate results due to fast acting Testosterone Acetate and Propionate. Additionally, the slow tapering effect caused by... 

---