1159-66-6

Usage

Uses

Used in Pharmaceutical Industry:
(3S,8R,9S,10R,13S,14S,17R)-3,17-dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,17-dodecahydrocyclopenta[a]phenanthren-16-one is used as a pharmaceutical agent for its potential biological activities. Given its classification as an androstane steroid, it may have implications in hormone regulation and cellular signaling, making it a candidate for the development of drugs targeting various physiological processes.
Used in Research Applications:
In the field of scientific research, (3S,8R,9S,10R,13S,14S,17R)-3,17-dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,17-dodecahydrocyclopenta[a]phenanthren-16-one is used as a research tool to study the structure-activity relationships of androstane steroids. Its unique features can provide insights into the molecular mechanisms underlying the biological functions of this class of compounds, potentially leading to the discovery of novel therapeutic agents or a better understanding of physiological processes.

InChI:InChI=1/C19H28O3/c1-18-6-5-15-14(16(18)8-13(21)10-18)4-3-11-7-12(20)9-17(22)19(11,15)2/h9,11,13-16,20-21H,3-8,10H2,1-2H3/t11?,13-,14-,15+,16+,18-,19+/m1/s1

Upstream product

• 1093-91-0 3β-hydroxy-16α-bromoandrost-5-ene-17-one 
• 18878-68-7 16-(1β-Hydroxy-ethyl)-3β,16α,17-trihydroxy-androsten-(5) 
• 979-62-4 3β-acetoxy-5α,6β-dichloroandrostan-17-one 
• 96370-11-5 3β,16α-Diacetoxy-5α,6β-dichlor-androstan-17-on 
• 1122098-27-4 C₁₉H₂₇⁽²⁾HO₃ 
• 1232-73-1 16α-hydroxy dehydroepiandrosterone 
• 74644-60-3 16β-bromo-3β-hydroxy-5-androsten-17-one 
• 53-43-0 dehydroepiandrosterone 
• 96442-97-6 3β,16β-Diacetoxy-5α,6β-dichlor-androstan-17-on 
• 17975-95-0 5α,6β-dichloroandrost-16-en-3β,17-diol diacetate 
• 18878-64-3 16-Acetyl-3β,16,17-triacetoxy-androsten-(5) 
• 18944-55-3 16-(1β-Hydroxy-aethyl)-3β,16α,17-trihydroxy-androsten-(5)-acetonid 
• 5297-31-4 1-(17-amino-3β-hydroxy-androsta-5,16-dien-16-yl)-ethanone 
• 23357-24-6 3β,16β-diacetoxy-17α-hydroxypregn-5-en-20-one 

Downstream Products

• 14474-06-7 5-androsten-3β,16β,17β-triol 
• 14072-21-0 3β-Hydroxy-5-androsteno-16,17-dione-17-phenylhydrazone-16-p-nitrophenylhydrazone 
• 14072-22-1 3β-Hydroxy-5-androsten-16,17-dione-16-p-nitrophenylhydrazone 
• 2099-26-5 androstenediol-3,17-diacetate 
• 17980-97-1 3β-benzoyloxy-androst-5-en-16-one 
• 5088-64-2 3β-hydroxy-5-androsten-16-one 
• 79884-22-3 16β-acetoxy-3β,17β-bis(tetrahydro-2-pyranyloxy)-15α-tolylsulfonyloxymethyl-5-androstene 
• 79884-27-8 3β,17β-bis(tetrahydro-2-pyranyloxy)-15α-tolylsulfonyloxy-5-androsten-16β-ol 
• 104921-07-5 3β,17β-Dihydroxy-5-androsten-16-one Phenylhydrazone 

Relevant academic research and scientific papers

Mechanistic aspects of rearrangement of 16α-hydroxy-17-keto steroids to the 17β-hydroxy-16-keto isomers

The mechanistic aspects of the alkali-catalyzed rearrangement of 16α-hydroxy-17-keto steroid 1 to 17β-hydroxy-16-keto steroid 2 are elucidated by use of 18O- and deuterium-labeling experiments. The 18O-labeling experiments refute the gem-hydration-quasi-diaxial dehydration mechanism for the rearrangement previously proposed and support the conventional enolization mechanism. Moreover, equilibrium by gem-hydration-dehydration occurs at the C-17 carbonyl more efficiently than at the C-16 carbonyl. Enolization rate of a carbonyl group at C-16 of 17β-ketol 2 toward the C-17 position (k16,17) was about 8-10 times higher than those of 16α-ketol 1 toward the C-16 position (k17,16) and ketol 2 toward the C-15 position (k16,15). The marked deuterium-isotope effect on each enolization was observed with kH/kD ranging between 5.4 and 8.8. The present findings reveal that the initial hydration-dehydration equilibration at the C-17 carbonyl of ketol 1 followed by enolization of the carbonyl gives the ene-diol intermediate that isomerizes quantitatively to the 16-keto isomer of which the 16-carbonyl moiety enolizes preferentially toward the C-17 position rather than the C-15 position, yielding the ene-diol. Computational calculations of ground state energies of ketols 1-M and 2-M, trans-cyclohexane/cyclopentane structures, and their activation energies in the rearrangement support the dynamic aspects of the rearrangement as well as the kinetics data of the enolization.

CONTROLLED ALKALINE HYDROLYSIS OF STEROIDAL α-BROMOKETONES: NEW CONDITIONS AND SYNTHESIS OF 2α-HYDROXY-3-ONES

Controlled alkaline hydrolysis of 16α-bromo-17-keto steroids 1, 5 and 7 with potassium carbonate and tetra-n-butylammonium hydroxide (n-Bu4NOH) and synthesis of 2α-hydroxy-3-ones 11, 13 and 16 by the controlled hydrolysis of the corresponding 2α-bromo-3-ones 9, 12 and 15 are described.Treatment of the bromoketones 1, 5 and 7 with potassium carbonate in aqueous acetone or with n-Bu4NOH in aqueous dimethylformamide (DMF) gave 16α-hydroxy-17-ones 3, 6 and 8 in 85-90percent yield, respectively. 2α-Hydroxy-3-ones 11, 13 and 16 were obtained by hydrolysis of the corresponding bromoketones 9, 12 and 15 in high yields using the above conditions or sodium hydroxide in pyridine or DMF, respectively.Deuterium labeling experiments suggested that equilibration between the 2α-bromoketone 9 and the 2β-bromo isomer 10 precedes the formation of the ketol 11 in which the true intermediate might be the 2β-isomer 10.However, rearranged androstane derivatives, 3β-hydroxy-2-ones 18 and 20, were stereoselectively obtained by treatment of the bromoketones 12 and 15 with an excess amount of sodium hydroxide.

C19-Steroids as androgen receptor modulators: Design, discovery, and structure-activity relationship of new steroidal androgen receptor antagonists

Dehydroepiandrosterone (DHEA), the most abundant steroid in human circulating blood, is metabolized to sex hormones and other C19-steroids. Our previous collaborative study demonstrated that androst-5-ene-3β,17β-diol (Adiol) and androst-4-ene-3,17-dione (Adione), metabolites of DHEA, can activate androgen receptor (AR) target genes. Adiol is maintained at a high concentration in prostate cancer tissue; even after androgen deprivation therapy and its androgen activity is not inhibited by the antiandrogens currently used to treat prostate cancer patients. We have synthesized possible metabolites of DHEA and several synthetic analogues and evaluated their role in androgen receptor transactivation to identify AR modulators. Steroids with low androgenic potential in PC-3 cell lines were evaluated for anti-dihydrotestosterone (DHT) and anti-Adiol activity. We discovered three potent antiandrogens: 3β-acetoxyandrosta-1,5-diene-17-one 17-ethylene ketal (ADEK), androsta-1,4-diene-3,17-dione 17-ethylene ketal (OAK), and 3β-hydroxyandrosta-5,16-diene (HAD) that antagonized the effects of DHT as well as of Adiol on the growth of LNCaP cells and on the expression of prostate-specific antigen (PSA). In vivo tests of these compounds will reveal their potential as potent antiandrogens for the treatment of prostate cancer.

Production of 16β-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid enol acetates with lead (IV) acetate

Treatment of enol acetates of 3β-acetoxyandrost-5-en-17-one and its 5α-reduced analog, 5α-androstan-17-one, and estrone acetate, 1-4, with Pb(OCOCH3)4 in acetic acid and acetic anhydride gave the previously unreported products, 16β-(acetoxy)acetoxy-17-ketones 8-10 and 12, in 9-15% yields along with the known major products, 16β-acetoxy-17-ketones 5-7 and 11. Similar treatment of the 16β-acetoxy-17-ketones with the lead reagent did not yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with Pb(OCOCD3)4 in CD3COOD yielded principally the labeled (acetoxy)acetate 10-d3, which had a CD3COOCH2COO moiety at C-16β. In contrast, when the deuterated enol acetate 3-d3, which was obtained by treatment of the 17-ketone 14 with (CD3CO)2O in the presence of LDA and which had a CD3COO moiety at C-17, was reacted with Pb(OCOCH3)4, the resulting product was the labeled compound 10-d2. This product had a CH3COOCD2COO function at C-16β. Based on these results, along with further isotope-labeling experiments, it seems likely that the (acetoxy)acetate is produced through a lead (IV) acetate-catalyzed migration of the 17-acetyl function of the enol acetate to the C-16β-position followed by attack of an acetoxy anion of the lead reagent. Copyright

Steroids, L. Ring D Cleavage of D-Trisubstituted Steroids

In alkaline medium, 3β,17β-dihydroxy-15-(hydroxymethylene)androst-5-en-16-one (2a) is cleaved in two ways to give D-seco compounds.Dilute bases in protic solvents cause 1,3-dicarbonyl splitting to the 15-formyl-15,16-seco-16-oic acid 3, while the use of sodium methanolate in benzene solution gives rise to 16,17-splitting to afford the 15-formyl-16,17-seco-16,17-dioic acid 5.Both seco compounds redily undergo lactolone ring closure to give 4a and 6a, respectively.The malonaldehyde moiety of 5 is transformed in two directions: either loss of the formyl group to give 3β-hydroxy-16,17-secoandrost-5-ene-16,17-dioic acid (7a) or decarboxylation to 3β-hydroxy-16-oxo-16,17-secoandrost-5-en-17-oic acid (9) is observed. Key Words: Steroids/ 15-Hydroxymethylene-16-ketosteroids/ D-seco-steroids/ D-Homo-oxa-steroids

Stereospecific Synthesis of 16α-Hydroxy-17-oxo Steroids by Controlled Alkaline Hydrolysis of Corresponding 16-Bromo 17-Ketones and Its Reaction Mechanism

Synthesis of 16α-hydroxy-17-oxo steroids 3, 5b, and 3β,16α-dihydroxy-5-17-oxoandrosten-3-yl sulfate (7) from 16α-bromo-17-oxo steroids 1, 5a, and 6a and the reaction mechanism of the controlled alkaline hydrolysis are described.Treatment of the bromo ketones with NaOH in aqueous DMF gave the 16α-hydroxy 17-ketones stereoselectively in 95percent yield without formation of other ketols.The sodium salt of 3-sulfate 7 was also obtained in one step in 85percent yield from the corresponding bromo ketone (1a).Isotope-labeling experiments and time-course studies showed that equilibration between the 16-bromo epimers 1 and 2 precedes the formation of 3, in which the true intermediate is 2 and not 1, and that the ketol 3 is formed by the direct SN2 displacement of the 16β-bromine.The 16β-morpholino derivative 8 obtained by reaction of 1 with morpholine was shown to be an isomerized product of the 16α isomer which is produced also by SN2 displacement of the 16β-bromine.The mechanism of ketol rearrangement of 3 to the 17β-hydroxy-16-oxo compound 4 was found to involve a hydration to the carbonyl function.The new hydration-dehydration mechanism is proposed for the ketol rearrangement.