Neighboring group participation: Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5α-reductase

J. Wölfling, László Hackler, E. Mernyák, G. Schneider, István Tóth, Mihály Szécsi, J. Julesz, P. Sohár, A. Csámpai

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Abstract

During the alkaline methanolysis of 3β-acetoxy-21-chloromethyl-pregn- 5-ene-20β-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17β-[3-(N-phenyl) tetrahydrooxazin-2-on-6-yl]androst-5-en-3β-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N--6) neighboring group participation. Oppenauer oxidation of the 3β-hydroxy-exo- heterocyclic steroids yielded the corresponding Δ4-3- ketosteroids. The structures of the new compounds were proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI 50) of the Δ4-3-ketosteroids on 5α-reductase were studied.

Original languageEnglish
Pages (from-to)451-460
Number of pages10
JournalSteroids
Volume69
Issue number7
DOIs
Publication statusPublished - Jul 2004

Fingerprint

Ketosteroids
Cyclization
Heterocyclic Steroids
Oxidoreductases
Derivatives
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Oxidation
androst-5-en-3-ol
vitamin B 12 factor III
phenylurethane
Proton Magnetic Resonance Spectroscopy
Carbon-13 Magnetic Resonance Spectroscopy
cyclo(Arg-Pro)

Keywords

  • 5α-Reductase
  • Heterocyclic steroids
  • In vitro inhibition
  • Neighboring group participation
  • Structure determination by IR and NMR

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

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title = "Neighboring group participation: Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5α-reductase",
abstract = "During the alkaline methanolysis of 3β-acetoxy-21-chloromethyl-pregn- 5-ene-20β-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17β-[3-(N-phenyl) tetrahydrooxazin-2-on-6-yl]androst-5-en-3β-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N--6) neighboring group participation. Oppenauer oxidation of the 3β-hydroxy-exo- heterocyclic steroids yielded the corresponding Δ4-3- ketosteroids. The structures of the new compounds were proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI 50) of the Δ4-3-ketosteroids on 5α-reductase were studied.",
keywords = "5α-Reductase, Heterocyclic steroids, In vitro inhibition, Neighboring group participation, Structure determination by IR and NMR",
author = "J. W{\"o}lfling and L{\'a}szl{\'o} Hackler and E. Merny{\'a}k and G. Schneider and Istv{\'a}n T{\'o}th and Mih{\'a}ly Sz{\'e}csi and J. Julesz and P. Soh{\'a}r and A. Cs{\'a}mpai",
year = "2004",
month = "7",
doi = "10.1016/j.steroids.2004.04.003",
language = "English",
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pages = "451--460",
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T2 - Part 15. Stereoselective synthesis of some steroidal tetrahydrooxazin-2-ones, as novel presumed inhibitors of human 5α-reductase

AU - Wölfling, J.

AU - Hackler, László

AU - Mernyák, E.

AU - Schneider, G.

AU - Tóth, István

AU - Szécsi, Mihály

AU - Julesz, J.

AU - Sohár, P.

AU - Csámpai, A.

PY - 2004/7

Y1 - 2004/7

N2 - During the alkaline methanolysis of 3β-acetoxy-21-chloromethyl-pregn- 5-ene-20β-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17β-[3-(N-phenyl) tetrahydrooxazin-2-on-6-yl]androst-5-en-3β-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N--6) neighboring group participation. Oppenauer oxidation of the 3β-hydroxy-exo- heterocyclic steroids yielded the corresponding Δ4-3- ketosteroids. The structures of the new compounds were proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI 50) of the Δ4-3-ketosteroids on 5α-reductase were studied.

AB - During the alkaline methanolysis of 3β-acetoxy-21-chloromethyl-pregn- 5-ene-20β-N-phenylurethane, and its p-substituted phenyl derivatives, cyclization occurs, in the course of which 17β-[3-(N-phenyl) tetrahydrooxazin-2-on-6-yl]androst-5-en-3β-ol and its p-substituted phenyl derivatives are formed. The cyclization takes place with (N--6) neighboring group participation. Oppenauer oxidation of the 3β-hydroxy-exo- heterocyclic steroids yielded the corresponding Δ4-3- ketosteroids. The structures of the new compounds were proved by IR, 1H and 13C NMR spectroscopy, using up-to-date measuring techniques such as 2D-COSY, HMQC, and HMBC. The inhibitory effects (CI 50) of the Δ4-3-ketosteroids on 5α-reductase were studied.

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KW - In vitro inhibition

KW - Neighboring group participation

KW - Structure determination by IR and NMR

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