Concise synthesis of 23-hydroxylated vitamin D3 metabolites

Fumihiro Kawagoe; Toru Sugiyama; Kaori Yasuda; Motonari Uesugi; Toshiyuki Sakaki; Atsushi Kittaka

doi:10.1016/j.jsbmb.2018.10.010

Concise synthesis of 23-hydroxylated vitamin D₃ metabolites

J Steroid Biochem Mol Biol. 2019 Feb:186:161-168. doi: 10.1016/j.jsbmb.2018.10.010. Epub 2018 Oct 24.

Authors

Fumihiro Kawagoe¹, Toru Sugiyama², Kaori Yasuda³, Motonari Uesugi⁴, Toshiyuki Sakaki³, Atsushi Kittaka⁵

Affiliations

¹ Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; AMED-CREST, AMED, Japan.
² Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
³ Faculty of Engineering, Toyama Prefectural University, Imizu, Toyama 939-0398, Japan.
⁴ AMED-CREST, AMED, Japan; Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
⁵ Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan; AMED-CREST, AMED, Japan. Electronic address: akittaka@pharm.teikyo-u.ac.jp.

PMID: 30367940
DOI: 10.1016/j.jsbmb.2018.10.010

Abstract

Three 23-hydroxylated vitamin D₃ derivatives, which are metabolites of 25-hydroxyvitamin D₃ produced by CYP24A1 and a related diastereomer, were efficiently synthesized. Each C23 hydroxy unit was constructed by the Claisen condensation reaction with ethyl acetate or the Grignard reaction with 2-methylallymagnesium chloride. Stereochemistry at the C23 position was determined by a modified Mosher's method. The triene structures were constructed by the Wittig-Horner reaction utilizing the A-ring phosphine oxide moiety.

Keywords: 23-Hydroxyvitamin D(3); Modified Mosher’s method; Synthesis; Vitamin D(3) metabolite.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcifediol / analogs & derivatives
Calcifediol / metabolism*
Chemistry Techniques, Synthetic
Dihydroxycholecalciferols / chemical synthesis*
Dihydroxycholecalciferols / chemistry
Hydroxycholecalciferols / chemical synthesis*
Hydroxycholecalciferols / chemistry
Stereoisomerism
Vitamin D3 24-Hydroxylase / metabolism

Substances

Dihydroxycholecalciferols
Hydroxycholecalciferols
23,25-dihydroxyvitamin D3
23,25,26-trihydroxyvitamin D3
Vitamin D3 24-Hydroxylase
Calcifediol