Improved Synthesis and Molecular Modeling of 4β,19-Dihydroxyandrost-5-en-17-one, an Excellent Inhibitor of Aromatase

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概要

• 論文の詳細を見る

• 4β,19-Dihydroxyandrost-5-en-17-one (6) is an excellent competitive inhibitor of estrogen synthetase (aromatase). Alternate, improved synthesis of this inhibitor was established. Treatment of 19-(tert-butyldimethylsilyloxy)androst-4-en-17-one (8) with m-chloroperbenzoic acid gave a 1.4:1 mixture of 4α,5α-epoxide 9 and its 4β,5β-isomer 10. The mixture was reacted with dil. HCIO_4 in dioxane to produce principally 4β,5α-diol 11(80%) of which acetylation followed by dehydration with SOCI_2 yielded 4β,19-diacetoxy-5-ene compound 14 in good yield. Alkaline hydrolysis of diacetate 14 gave 4β,19-diol 6. The minimum energy conformation of the powerfull aromatase inhibitor 6 was obtained with the PM3 method and compared with that of the structurally related diol steroid, 4-ene-5β,19-diol 3, a weak competitive inhibitor.

• 公益社団法人日本薬学会の論文
• 2002-05-01

著者

• 沼沢 光輝

  Tohoku Pharmaceutical University

• NUMAZAWA Mitsuteru

  Tohoku College of Pharmacy

• Nagaoka Masao

  Tohoku College Of Pharmacy:sankyo Co. Ltd.

• YAMADA Keiko

  Tohoku Pharmaceutical University

• WATARI Yoko

  Tohoku Pharmaceutical University

• ANDO Momoko

  Tohoku Pharmaceutical University

• Watari Y

  Tohoku Pharmaceutical University

• Yamada Keiko

  Tohoku College Of Pharmacy

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