Potential corticoid metabolites: Chemical synthesis of 3- and 21-monosulfates and their double-conjugates of tetrahydrocorticosteroids in the 5 α- and 5 β-series

Rika Okihara, Kuniko Mitamura, Maki Hasegawa, Megumi Mori, Akina Muto, Genta Kakiyama, Shoujiro Ogawa, Takashi Iida, Miki Shimada, Nariyasu Mano, Shigeo Ikegawa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Here, we describe the chemical synthesis of the complete sets of 18 novel 3- and 21-monosulfates and their double-conjugated form of tetrahydrocortisol (THF), tetrahydro-11-deoxycortisol (THS), and tetrahydrocortisone (THE) in the 5 α- and 5 β-series. The principal reactions involved are: (1) selective protection of a specific hydroxy group in substrates; (2) catalytic hydrogenation at C-5 of Δ4-3-ketosteroids with 10% Pd(OH) 2/C to yield 3-oxo-5 β-steroids and reductive allomerization with 10% Pd/C to yield 3-oxo-5 α-isomers; (3) reduction of the resulting 3-oxo-5 β- and 3-oxo-5 α-steroids to the corresponding 3 α-hydroxy-compounds with Zn(BH4)2 and K-Selectride®, respectively; and (4) sulfation of hydroxy groups at C-3 and/or C-21 in the tetrahydrocorticosteroid derivatives with sulfur trioxide-triethylamine complex.

Original languageEnglish
Pages (from-to)344-353
Number of pages10
JournalChemical and Pharmaceutical Bulletin
Volume58
Issue number3
DOIs
Publication statusPublished - 2010 Mar

Keywords

  • Catalytic reduction
  • Sulfate
  • Sulfur trioxide-triethylamine complex
  • Tetrahydro-11-deoxycortisol
  • Tetrahydrocortisol
  • Tetrahydrocortisone

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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