1 6-Hydroxy- 17-Ketosteroid

Hydroxysteroid dehydrogenases are widely distributed among rat tissue. They have been found in liver, kidney, placenta, and peripheral tissue. Prolonged treatment of mice with cortisol increases the ability of the thymus but not that of spleen and lymph nodes to convert cortisol to cortisone. The 11-hydroxy-ketosteroid dehydrogenase requires NAD or NADP as coenzyme. 

A rhythmic variation has been observed in levels of plasma hydroxy-corticosteroids (A9, B13, D9) and in the excretion of 17-ketosteroids (P7). As shown in Table 5, urinary excretions of potassium, sodium, chloride, 17-hydroxycorticosteroids and water have been reported to be greatest between 10 am to noon and lowest between 4 am and 6 am (S21). In this study it was shown that within 5 weeks subjects could acclimate to similar patterns for a 21-hour, rather than a 24-hour, day. Heilman and his associates reported that about half of the day s cortisol production is achieved in the early morning hours during sleep and that production is minimal between noon and 10 pm (H7). In one study the plasma cortisol in normal men was 24.6 5.5 /xg/100 ml at 7 am 13.1 3.4 fig/100 ml at 9 am 11.8 fig/100 ml at noon 9.1 2.3 jag/100 ml at 7 PM and 6.3 /ig/100 ml at 10 pm (A9). 

Most glucocorticosteroid are metabolized in the liver to hydroxy- and ketosteroid metabolites which are excreted by the kidneys as glucuronides, sulfates and unconjugated products. Enzyme-inducing agents will diminish the efficacy of glucocorticosteroids. 

Keywords 17a-hydroxy-20-ketosteroid, acyloin rearrangement, substitutive rearrangement, stereoselective, gas-solid reaction... 

Six new 3p,5,6P-trihydroxysterols with a saturated nucleus have been isolated from two different populations of the sponge Cliona copiosa, collected from two different sites of the bay of Naples. Successively, several new D5-3p-hydroxy-7-ketosteroids and the related As-3p, 7p, and As-3p,7a-dihydroxysteroids have been described as constituent of the same species. 

The method has been applied successfully to the determination of the A -3-ketosteroid content of oily injections where the solvent pair were dioxane and isopropanol [26]. Likewise 21-hydroxy- and 21-acetoxycorticosteroids can be determined by means of ACD spectroscopy [27]. 

The a-ketol rearrangement65 is an isomerization reaction of a-hydroxy ketones (as well as aldehydes) which takes place under acid as well as base catalysis. Compound 11/71, a 17 a-hydroxy-20-ketosteroid, yields, under acid catalysis, the six-membered isomer 11/72, and under base catalysis, the mixture of the isomeric compounds 11/73, as reviewed in [1],... 

Deoxygenation." The 17a-hydroxy group of 17a,21-dihydroxy-20-ketosteroids is selectively reduced by ISi(CH,), in CH,CN at room temperature (equation I). A free 21-hydroxyl group is necessary for this dehydroxylation. 

Hydroxy-2Q-ketosteroids.1 C17-Ketosteroids (1) undergo a Knoevenagel-type condensation with TosMIC to provide 17-(isocyanotosylmethylene)steroids (2). Phase-transfer catalyzed alkylation of 2 with formaldehyde gives an oxazoline, which is hydro-... 

I7(x-Methyl-17 -hydroxy-estra-4,9,l l-trien-3-one (Methyltrienolone, N-99). In the course of a steroid total synthesis [293] this compound (Methyltrienolone, N-99) was prepared it was reported [55] to possess 6000% of the androgenic (ventral prostate index), 7500% of the androgenic (seminal vesicles index), and 12,000% of the anabolic (levator ani index) activity of methyltestosterone. Later the anabolic activity was reported [74] to be 30,000% of that of methyltestosterone. As measured by multiple parameters methyltrienolone turned out to be the most hepatotoxic steroid, causing biochemical symptoms of intrahepatic cholestasis [75]. It was also reported [74] to reduce the excretion of 17-ketosteroids and 17-hydroxycorticosteroids and to cause enhancement of the blood coagulation factors V, VII, and X. It also increases the prothrombin content of the plasma [74]. 

Ether formation often leads to enhanced oral activity. 17/8-Hydroxy-5a-androstan-3-one 17-(rmethoxy)cyclopentyl ether (D-130), 17)3-hydroxy-5a-androstan-3-one 17-(l -ethoxy)cyclopentyI ether (D-132), 17j3-hydroxy-5a-androst-l-en-3-one 17-(r-ethoxy)cyclopentyl ether (A-163), and 17j3-hydroxy-5a-androst-l-en-3-one 17-cyclopent-r-enyl ether (A-164) are all reported to possess favorable anabolic-androgenic ratios with increased anabolic and androgenic properties. The enhancement of oral activity is interesting in view of the fact that the ether bond of these compounds is easily broken, as manifested by the strongly enhanced excretion of 17-ketosteroids in humans treated with the ether derivatives [144]. 

The reagent converts 17-ketosteroids into 17 S,20-epoxy-21-norpregnane derivatives reducible to l7/3-hydroxy-17o -methylsteroids. ... 

In contrast to the usual reduction of 3-ketosteroids to 3 -hydroxysteroids, 5(io) gjtrene-3,17-dione (6) is reduced by lithium tri-/-butoxyaluminum hydride to the 3 a- and 3 -hydroxy derivatives in the ratio 15 1. ... 

Hydroxy-A <-3-ketosteroids, 60 2a-Hydroxy-A- 3-ketosterolds, 59-60 4-Hydroxy-A -3-ketosteroids, 72, 921 12-Hydroxy-ll-ketosteroids, 59 17a-Hydroxy-20-ketosteroids, 786, 949 Hydroxylaminedisulfonic acid, sodium salt, 670... 

The oxide is a specific reagent for oxidation of acyloins to a-diketones, the oxide being reduced to the metal. A solution of the acyloin in acetic acid is treated with 1.2 times the theoretical amount of BijOj and the mixture is heated on the steam bath with stirring for about 15 min. Benzoin—> benzil (95% yield). 12-Hydroxy-11-ketosteroids —> 11,12-diketosteroids (70% yield)." Oxidation of cevine and isomers." Other examples are the oxidation of 2-hydroxypulegone (I) to diosphenolone (2) in 94%i yield (crude), of Ihe 2 -hydroxy-A -3-ketosteroid (3) to (4)," and of (5) to (6)."... 

The behavior of A -3-ketosteroids on oxidative cleavage - is illustrated by the reaction of testosterone propionate (1). Pettit and Kasturi mixed 9 g. of potassium persulfate and 10 g. of coned, sulfuric acid in a mortar, diluted with 150 ml. of acetic acid, added the mixture to a solution of 9 g. of testosterone propionate in 150 ml. of acetic acid, and let the mixture stand with intermittent shaking at room temperature for 7 days. Workup included saponification and reacidifleation, and the product (2 g.) was characterized as the lactone 3-oxo-17/3-hydroxy-4-oxa-5a-androstane (4). A possible reaction sequence is formulated. 

It has been proposed that there is a direct relationship between the inhibition of growth of mouse fibroblasts in vitro and the anti-inflammatory activity of llp-hydroxylated steroids. 11-Ketosteroids do not show this inhibition and thLs may be due to the lack of enzyme systems necessary to convert 11-keto to lip-hydroxy steroids . 

Hydroxy- corticosteroids Apply sample then follow with 10% aqueous sodium periodate solution, allow to react, dry at 50°C and develop. 17-Ketosteroids are produced. [3]... 

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