Improved chemical synthesis, X-ray crystallographic analysis, and NMR characterization of (22R)-/(22S)-hydroxy epimers of bile adics.
Improved chemical synthesis, X-ray crystallographic analysis, and NMR characterization of (22R)-/(22S)-hydroxy epimers of bile adics.
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改进了胆汁酸 (22R)-/(22S)-羟基差向异构体的化学合成、X 射线晶体分析和 NMR 表征。
DOI：
10.1007/s11745-014-3955-y
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
A. F.; Iida,T.
中科院分区：
文献类型：
--
作者：
Omura;K.; Ohsaki;A.; Zhou;B.; Kushida;M.; Mitsuma;T.; Kobayashi;A.; Hagey;L. R.; Hofmann;A. F.; Iida,T.
We report an improved synthesis of the (22R)‐ and (22S)‐epimers of 3α,7α,12α,22‐tetrahydroxy‐5β‐cholan‐24‐oic acid and 3α,7α,22‐trihydroxy‐5β‐cholan‐24‐oic acid from cholic acid (CA) and chenodeoxycholic acid (CDCA), respectively. The principal reactions involved were as follows: (1) oxidative decarboxylation of the bile acid peracetates with lead tetraacetate, and (2) subsequent Reformatsky reaction of the 23,24‐dinor‐22‐aldehydes with ethyl bromoacetate in the presence of activated Zn as a catalyst with the reaction temperature maintained precisely at 75 °C. The absolute configuration of the chiral center at C‐22 of each epimer was established by single‐crystal X‐ray diffraction data using its ethyl ester‐peracetate derivative. The1H‐ and13C‐NMR spectra that permit the (22R)‐ and (22S)‐epimers to be distinguished are reported as well as the specific1H shift effects induced by C5D5N. Bile acids having hydroxyl groups at C‐22 are present in a variety of animal biles, previously have been difficult to identify, and are known to have distinctive physicochemical and biological properties.
