Addition reactions at the 16(17) double bond of 3-methoxy-13α-estra-1,3,5(10),16-tetraene

E. Mernyák, Bruno Schönecker, Corinna Lange, Manuela Kötteritzsch, Helmar Görls, J. Wölfling, G. Schneider

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The epoxidation, the addition of hypobromous acid, and the hydroboration of 3-methoxy-13α-estra-1,3,5(10),16-tetraene 1 with diborane, catecholborane, and 9-BBN were investigated in order to determine the stereochemical outcome and to synthesize new 13α-estra-1,3,5(10)-trienes for biological and conformational investigations. It was shown that the sterically demanding reagent 9-BBN participated in a preferred β attack (53% 16βOH 10, 34% 17βOH 8, 13% 16αOH 11). This stereochemical result is in agreement with that from another cis addition reaction, the recently described OsO4 dihydroxylation of 1 [Steroids 68 (2003) 113]. With smaller reagents such as B2H6, catecholborane, or magnesium monoperoxyphthalate, a diminished stereoselectivity was observed with only a slight excess of β attack. The ionic trans addition of hypobromous acid gave two 17-bromo-16-alcohols with 16β,17α (4, 76%) and 16α,17β configuration (5, 24%) formed by trans cleavage of the 16,17α- and β-bromonium ion at position 16. The same regioselective and stereoselective course was found for the cleavage of the 16α,17α- and 16β,17β-epoxides (3 and 2) with hydrazoic acid (3→16βN3,17αOH 7, 2→16αN3,17βOH 6). The stereochemistry of the addition reactions to 1 can be explained in terms of a twist-boat conformation involving the C ring of compound 1. From a synthetic viewpoint the synthesis of the β-epoxide 2 from the bromohydrin 4, the cleavage of this epoxide to 16α-substituted-17β-hydroxy compounds, such as 6, and hydroboration/oxidation with 9-BBN to the hitherto unknown 16β-hydroxy compound 10 are useful procedures. The bromohydrin 5 is the first 13α-steroid with a 17β-bromo substituent. X-ray analysis revealed twist-boat and 16β-envelope conformations for rings C and D, respectively.

Original languageEnglish
Pages (from-to)289-295
Number of pages7
JournalSteroids
Volume68
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

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Addition reactions
Epoxy Compounds
Ships
Boats
Conformations
Steroids
Stereoselectivity
Stereochemistry
Epoxidation
X ray analysis
Alcohols
X-Rays
Ions
Oxidation
hypobromous acid
bromohydrins

Keywords

  • 13α-Estra-1,3,5(10)-trienes
  • Addition reactions
  • Conformation
  • Stereochemistry
  • Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Addition reactions at the 16(17) double bond of 3-methoxy-13α-estra-1,3,5(10),16-tetraene. / Mernyák, E.; Schönecker, Bruno; Lange, Corinna; Kötteritzsch, Manuela; Görls, Helmar; Wölfling, J.; Schneider, G.

In: Steroids, Vol. 68, No. 3, 01.03.2003, p. 289-295.

Research output: Contribution to journalArticle

Mernyák, E. ; Schönecker, Bruno ; Lange, Corinna ; Kötteritzsch, Manuela ; Görls, Helmar ; Wölfling, J. ; Schneider, G. / Addition reactions at the 16(17) double bond of 3-methoxy-13α-estra-1,3,5(10),16-tetraene. In: Steroids. 2003 ; Vol. 68, No. 3. pp. 289-295.
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abstract = "The epoxidation, the addition of hypobromous acid, and the hydroboration of 3-methoxy-13α-estra-1,3,5(10),16-tetraene 1 with diborane, catecholborane, and 9-BBN were investigated in order to determine the stereochemical outcome and to synthesize new 13α-estra-1,3,5(10)-trienes for biological and conformational investigations. It was shown that the sterically demanding reagent 9-BBN participated in a preferred β attack (53{\%} 16βOH 10, 34{\%} 17βOH 8, 13{\%} 16αOH 11). This stereochemical result is in agreement with that from another cis addition reaction, the recently described OsO4 dihydroxylation of 1 [Steroids 68 (2003) 113]. With smaller reagents such as B2H6, catecholborane, or magnesium monoperoxyphthalate, a diminished stereoselectivity was observed with only a slight excess of β attack. The ionic trans addition of hypobromous acid gave two 17-bromo-16-alcohols with 16β,17α (4, 76{\%}) and 16α,17β configuration (5, 24{\%}) formed by trans cleavage of the 16,17α- and β-bromonium ion at position 16. The same regioselective and stereoselective course was found for the cleavage of the 16α,17α- and 16β,17β-epoxides (3 and 2) with hydrazoic acid (3→16βN3,17αOH 7, 2→16αN3,17βOH 6). The stereochemistry of the addition reactions to 1 can be explained in terms of a twist-boat conformation involving the C ring of compound 1. From a synthetic viewpoint the synthesis of the β-epoxide 2 from the bromohydrin 4, the cleavage of this epoxide to 16α-substituted-17β-hydroxy compounds, such as 6, and hydroboration/oxidation with 9-BBN to the hitherto unknown 16β-hydroxy compound 10 are useful procedures. The bromohydrin 5 is the first 13α-steroid with a 17β-bromo substituent. X-ray analysis revealed twist-boat and 16β-envelope conformations for rings C and D, respectively.",
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AU - Mernyák, E.

AU - Schönecker, Bruno

AU - Lange, Corinna

AU - Kötteritzsch, Manuela

AU - Görls, Helmar

AU - Wölfling, J.

AU - Schneider, G.

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N2 - The epoxidation, the addition of hypobromous acid, and the hydroboration of 3-methoxy-13α-estra-1,3,5(10),16-tetraene 1 with diborane, catecholborane, and 9-BBN were investigated in order to determine the stereochemical outcome and to synthesize new 13α-estra-1,3,5(10)-trienes for biological and conformational investigations. It was shown that the sterically demanding reagent 9-BBN participated in a preferred β attack (53% 16βOH 10, 34% 17βOH 8, 13% 16αOH 11). This stereochemical result is in agreement with that from another cis addition reaction, the recently described OsO4 dihydroxylation of 1 [Steroids 68 (2003) 113]. With smaller reagents such as B2H6, catecholborane, or magnesium monoperoxyphthalate, a diminished stereoselectivity was observed with only a slight excess of β attack. The ionic trans addition of hypobromous acid gave two 17-bromo-16-alcohols with 16β,17α (4, 76%) and 16α,17β configuration (5, 24%) formed by trans cleavage of the 16,17α- and β-bromonium ion at position 16. The same regioselective and stereoselective course was found for the cleavage of the 16α,17α- and 16β,17β-epoxides (3 and 2) with hydrazoic acid (3→16βN3,17αOH 7, 2→16αN3,17βOH 6). The stereochemistry of the addition reactions to 1 can be explained in terms of a twist-boat conformation involving the C ring of compound 1. From a synthetic viewpoint the synthesis of the β-epoxide 2 from the bromohydrin 4, the cleavage of this epoxide to 16α-substituted-17β-hydroxy compounds, such as 6, and hydroboration/oxidation with 9-BBN to the hitherto unknown 16β-hydroxy compound 10 are useful procedures. The bromohydrin 5 is the first 13α-steroid with a 17β-bromo substituent. X-ray analysis revealed twist-boat and 16β-envelope conformations for rings C and D, respectively.

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KW - Stereochemistry

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