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 -Selective Agonist

被引：2
|
作者：
Koura, Minoru [1 ]
Sumida, Hisashi [1 ]
Shibuya, Kimiyuki [1 ]
Ohba, Shigeru [2 ]
机构：
[1] Kowa Co Ltd, Tokyo New Drug Res Labs, Div Pharmaceut, 2-17-43 Noguchicho, Tokyo 1890022, Japan
[2] Keio Univ, Res & Educ Ctr Nat Sci, Kohoku Ku, Hiyoshi 4-1-1, Yokohama, Kanagawa 2238521, Japan
来源：
SYNTHESIS-STUTTGART | 2017年 / 49卷 / 09期
关键词：
liver X receptor; hydantoin; X-ray crystal structure analysis; chiral synthesis; optical resolution; d-(-)-mandelic acid; ENANTIOSELECTIVE STRECKER REACTION; LFA-1 ANTAGONIST BIRT-377; OPTICAL RESOLUTION; EFFICIENT SYNTHESIS; MANDELIC-ACID; AMINO-ACIDS; KETOIMINES; DERIVATIVES; CATALYST; RING;
D O I：
10.1055/s-0036-1588700
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
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) -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 -selective agonist.
引用
收藏
页码：2074 / 2080
页数：7
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