Darstellung von mercapto‐substituierten 3‐Keto‐steroiden der Androstan‐Reihe

Krämer, Josef; Brückner, Klaus; Irmscher, Klaus; Bork, Karl‐Heinz

doi:10.1002/cber.19630961040

Cited by 15 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The major product eluted with a retention volume of 11.0 mL (eluent THF/hexane, 10:90 v/v) to give 8, with an Rt value of 0.52 (eluent ethyl acetate/hexane, 40:60 (G) 2-(Thioacetyl)-4-androsten-3-one 17-Acetate (9 and 10). Synthesis of 9 and 10 followed the procedure of Kramer et al (40). To a stirred solution of 8 (1.2 g, 2.6 mmol) in DMSO (16 mL) at room temperature was added potassium thioacetate (0.85 g, 7.4 mmol).…”

Section: Methodsmentioning

confidence: 99%

Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes

Underwood

Cashman²,

Correia³

1992

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Testosterone (T) 6 beta-hydroxylase (6 beta-OHase) is a well-recognized functional marker of rat liver cytochrome P450 3A (P450 3A) isozymes. Pretreatment of rats with inducers or specific or nonspecific inhibitors of P450 3A isozymes is associated not only with stimulation or inhibition of hepatic microsomal T 6 beta-OHase activity but also with parallel changes in the corresponding T 2 beta-, 15 beta-, and 18-OHase activities and T 4,6-diene formation. At the time these studies were conducted, no fully functionally active rat hepatic P450 3A isozymes had been isolated. To determine whether each of these activities was due to a single P450 3A isozyme, or whether multiple isozymes contributed to these activities, we specifically synthesized two thiotestosterone (6 beta- and 2 beta-SHT) analogues as potential mechanism-based inactivators of rat liver T 6 beta- and 2 beta-OHases. In addition, to assess their relative stereoselectivity, 2 alpha-SHT was also included as a control. Our studies revealed that although all three thiosteroids were excellent suicide substrates of P450 3A isozymes, they inactivated these T OHases differentially. Such differential inactivation and determination of the kinetic parameters of inactivation allowed the functional classification of rat hepatic P450 3A isozymes into at least two and possibly three categories: (i) forms (catalyzing 4,6-diene and 6 beta-OHT formation but with characteristically low 6 beta/2 beta-OHase ratios) highly susceptible to inactivation by SHTs; (ii) forms (catalyzing T 6 beta-, 2 beta-, 15 beta-, and 18-hydroxylations with high 6 beta-/2 beta-OHase ratios) moderately susceptible to the SHTs; and (iii) forms somewhat resistant to inactivation, at least at the SHT concentrations tested. Although no specific T OHase could be ascribed to a single P450 3A isozyme, it appears that each of these P450s catalyzed such T regiohydroxylations, albeit at considerably different extents. Furthermore, our studies also revealed that 2 alpha-SHT preferentially inactivated P450 3A forms but surprisingly failed to inactivate rat hepatic P450 2C11, thereby confirming the rather high substrate promiscuity of the P450 3A family of isozymes.

show abstract

Section: Methodsmentioning

confidence: 99%

Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes

Underwood

Cashman²,

Correia³

1992

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…Wie bei 6 beweisen UV-und 'H-NMR-Spektren, daO die Addition regio-und diastereoselektiv an die semicyclische Methylen-Gruppe erfolgt. Der NOE zwischen dem Singulett der 19-Methylprotonen und 2-H zeigt, daR 2a-Acetylthiomethyl-canrenon (8) vorliegt. Erhitzen von 7 rnit Thioessigsaure als Reagenz und Lose-mittel*) ergibt ein Bis-Addukt, das als Gemisch von 2 Diastereomeren anfallt.…”

unclassified

“…Durch zweifache SC an Kieselgel konnte das Hauptprodukt 9 in reiner Form isoliert werden (Schema 2). 8 …”

unclassified

Thioacetate aus Canrenon und 2‐Methylencanrenon

Görlitzer

Moormann

1995

Archiv der Pharmazie

View full text Add to dashboard Cite

Eingegangen am 13. Juli 1994Thioacetates from Canrenone and 2-Methylene Canrenone The 2a-bromo derivative 5, obtained from canrenone and dibromo meldrum acid, reacts with potassium thioacetate to yield the 2a-acetylthio compound 6. The mono-and bis-adducts 8 and 9 are produced from 2methylene canrenone and thioacetic acid.Das aus Canrenon und Dibrommeldrumsaure erhaltene 2a-Brom-Derivat 5 reagiert mit Kaliumthioacetat zur 2a-Acetylthio-Verbindung 6. Aus 2-Methylencanrenon lassen sich mit Thioessigsgure die Mono-und Bis-Addukte 8 und 9 darstellen.

show abstract

Darstellung von 7α‐Hydroxy‐ und 7α‐Methoxytestosteron‐Derivaten

et al. 1964

View full text Add to dashboard Cite

Die Anwendung der letztgenannten Verfahrensweise auf 6a.7a-Epoxy-17a-methyltestosteron (Ia)6) lieferte das bisher unbekannte 7a-Hydroxy-l7a-methyl-testosteron (Ira) in nur 7.5-proz. Ausbeute. In der Reduktion mit Lithium in fliissigern Ammoniak fanden wir eine priiparativ weit befriedigendere Reduktionsmethode, die I1 a in hoher Ausbeute ergab. Entsprechend konnte aus 6a.7a-Epoxy-testosteron (I b)7) 7a-Hydroxy-testosteron (I1 b) erhalten werden. 17-Ester des 6a.7a-Epoxy-testosterons (I&), d) iiberstanden die Reduktion bei kurzen Reaktionszeiten und knappem LithiumuberschuB im wesentlichen ohne Ver-1) J. A. CAMPBELL und J. C. BABCOCK, J. Amer. chem. Soc. 81,4069 [1959].

show abstract

Darstellung von mercapto‐substituierten 3‐Keto‐steroiden der Androstan‐Reihe

Cited by 15 publications

References 19 publications

Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes

Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes

Thioacetate aus Canrenon und 2‐Methylencanrenon

Darstellung von 7α‐Hydroxy‐ und 7α‐Methoxytestosteron‐Derivaten

Contact Info

Product

Resources

About