Synthesis, X-ray Crystal Structure and Antiestrogenic Activity of 17-Methyl-16,17-secoestra-1,3,5(10)-triene Derivatives

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Title:Synthesis, X-ray Crystal Structure and Antiestrogenic Activity of 17-Methyl-16,17-secoestra-1,3,5(10)-triene Derivatives
Creators:
Sakač, Marija N.
Miljković, Dušan A.
Penov Gaši, Katarina M.
Popsavin, Mirjana
Klisurić, Olivera R.
Stanković, Slobodanka M.
Andrić, Silvana
Kovačević, Radmila
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 70, 1, pp. 63-71
Uncontrolled Keywords:Antiestrogenic activity, Oximes, X-Ray analysis, Nitriles, Steroids, 17-Substituted 16,17-secosteroids, Aromatase inhibition

Abstract

Starting from 3-(benzyloxy)-16-(hydroxyimino)-estra-1,3,5(10)-trien-17-one (<strong>1</strong>) several 17-methyl-16,17-secoestratriene derivatives were synthesized. In the first step of synthesis, hydroxyimino ketone <strong>1</strong> was transformed into 3-(benzyloxy)-16-(hydroxyimino)-17α-methylestra-1,3,5(10)-trien-17β-ol (<strong>2</strong>), the Beckmann fragmentation of which gave 3-(benzyloxy)-17-methyl-17-oxo-16,17-secoestra-1,3,5(10)-triene-16-nitrile (<strong>3a</strong>). Reduction of <strong>3a</strong> with sodium borohydride yielded (17<i>S</i>)-3-(benzyloxy)-17-hydroxy-17-methyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile (<strong>4a</strong>), whose configuration at the newly formed chiral center was established by X-ray structural analysis. Catalytic hydrogenation of compound <strong>3a</strong> under different reaction conditions yielded 3-hydroxy-17-methyl-17-oxo-16,17-secoestra-1,3,5(10)-triene-16-nitrile (<strong>3b</strong>) and 16-amino-17-methyl-16,17-secoestra-1,3,5(10)-triene-3,17-diol (<strong>6b</strong>). Biological tests in vivo of compounds <strong>3b</strong> and <strong>6b</strong> showed their moderate antiestrogenic activity. <p>

Title:Synthesis, X-ray Crystal Structure and Antiestrogenic Activity of 17-Methyl-16,17-secoestra-1,3,5(10)-triene Derivatives
Creators:
Sakač, Marija N.
Miljković, Dušan A.
Penov Gaši, Katarina M.
Popsavin, Mirjana
Klisurić, Olivera R.
Stanković, Slobodanka M.
Andrić, Silvana
Kovačević, Radmila
Uncontrolled Keywords:Antiestrogenic activity, Oximes, X-Ray analysis, Nitriles, Steroids, 17-Substituted 16,17-secosteroids, Aromatase inhibition
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:70
Number:1
Page Range:pp. 63-71
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20050063UNSPECIFIED
ID Code:2343
Item Type:Article
Deposited On:06 Feb 2009 17:17
Last Modified:06 Feb 2009 16:17

Citation

Sakač, Marija N.; Miljković, Dušan A.; Penov Gaši, Katarina M.; Popsavin, Mirjana; Klisurić, Olivera R.; Stanković, Slobodanka M.; Andrić, Silvana; Kovačević, Radmila (2005) Synthesis, X-ray Crystal Structure and Antiestrogenic Activity of 17-Methyl-16,17-secoestra-1,3,5(10)-triene Derivatives. Collection of Czechoslovak Chemical Communications, 70 (1). pp. 63-71. ISSN 0010-0765

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