Determination of the Absolute Configuration and a Practical Chiral Synthesis of 5-[5-(1-Methylethoxy)pyridin-2-yl]-5-methyl­imidazolidine-2,4-dione as a Novel Liver X Receptor β-Selective Agonist

Minoru Koura, Hisashi Sumida, Kimiyuki Shibuya, Shigeru Ohba

Research output: Contribution to journalArticle

Abstract

We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.

Original languageEnglish
JournalSynthesis (Germany)
DOIs
Publication statusAccepted/In press - 2017 Jan 13

Fingerprint

Hydantoins
Liver
Hydrobromic Acid
Crystal structure
Propionates
Salts
X rays
Hydrogen
Acids

Keywords

  • chiral synthesis
  • d-(–)-mandelic acid
  • hydantoin
  • liver X receptor
  • optical resolution
  • X-ray crystal structure analysis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Cite this

@article{46d2040512e44b6986ebc4000258780f,
title = "Determination of the Absolute Configuration and a Practical Chiral Synthesis of 5-[5-(1-Methylethoxy)pyridin-2-yl]-5-methyl­imidazolidine-2,4-dione as a Novel Liver X Receptor β-Selective Agonist",
abstract = "We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99{\%} ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.",
keywords = "chiral synthesis, d-(–)-mandelic acid, hydantoin, liver X receptor, optical resolution, X-ray crystal structure analysis",
author = "Minoru Koura and Hisashi Sumida and Kimiyuki Shibuya and Shigeru Ohba",
year = "2017",
month = "1",
day = "13",
doi = "10.1055/s-0036-1588700",
language = "English",
journal = "Synthesis (Germany)",
issn = "0039-7881",
publisher = "Georg Thieme Verlag",

}

TY - JOUR

T1 - Determination of the Absolute Configuration and a Practical Chiral Synthesis of 5-[5-(1-Methylethoxy)pyridin-2-yl]-5-methyl­imidazolidine-2,4-dione as a Novel Liver X Receptor β-Selective Agonist

AU - Koura, Minoru

AU - Sumida, Hisashi

AU - Shibuya, Kimiyuki

AU - Ohba, Shigeru

PY - 2017/1/13

Y1 - 2017/1/13

N2 - We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.

AB - We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.

KW - chiral synthesis

KW - d-(–)-mandelic acid

KW - hydantoin

KW - liver X receptor

KW - optical resolution

KW - X-ray crystal structure analysis

UR - http://www.scopus.com/inward/record.url?scp=85011708533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011708533&partnerID=8YFLogxK

U2 - 10.1055/s-0036-1588700

DO - 10.1055/s-0036-1588700

M3 - Article

AN - SCOPUS:85011708533

JO - Synthesis (Germany)

JF - Synthesis (Germany)

SN - 0039-7881

ER -