[1]白晓杰,吴四维,周向东.用猪去氧胆酸立体选择性合成脑甾醇的新方法[J].第三军医大学学报,2016,38(11):1313-1318.
 Bai Xiaojie,Wu Siwei,Zhou Xiangdong.Stereoselective synthesis of cerebrosterol from porcine hyodeoxycholic acid[J].J Third Mil Med Univ,2016,38(11):1313-1318.
点击复制

用猪去氧胆酸立体选择性合成脑甾醇的新方法(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
38卷
期数:
2016年第11期
页码:
1313-1318
栏目:
药学
出版日期:
2016-06-15

文章信息/Info

Title:
Stereoselective synthesis of cerebrosterol from porcine hyodeoxycholic acid
作者:
白晓杰吴四维周向东
第三军医大学药学院药物化学教研室;重庆工商大学环境与生物工程学院应用化学系
Author(s):
Bai Xiaojie Wu Siwei Zhou Xiangdong

Department of Medicinal Chemistry, College of Pharmacy, Third Military Medical University, Chongqing, 400038;Department of Applied Chemistry, College of Environment and Biology, Chongqing Technology and Business University, Chongqing, 400067, China

关键词:
脑甾醇猪去氧胆酸乙酰链甾醇Sharpless不对称羟化反应立体选择性
Keywords:
cerebrosterol hyodeoxycholic acid desmosterol acetate Sharpless catalytic asymmetric dihydroxylation stereoselectivity
分类号:
R914.5; R927; R977.6
文献标志码:
A
摘要:

目的      探讨立体选择性合成脑甾醇的新方法。       方法      以猪去氧胆酸为原料,经甲酯化、还原、Wittig反应、Sharpless不对称双羟化等9步反应合成脑甾醇,其中以乙酰链甾醇为关键中间体,以Sharpless不对称双羟化反应为关键步骤。      结果      以52%的总收率、97%de的立体选择性合成脑甾醇,其结构用质谱(MS)、核磁共振氢谱(1HNMR)、核磁共振碳谱(13CNMR)、红外光谱(IR)和元素分析等证实。       结论      新的合成方法立体选择性高、收率高、每个中间体均为晶体易于重结晶纯化,可用于大量合成脑甾醇。

Abstract:

Objective      To establish a method to stereoselectively synthesize cerebrosterol.       Methods       The target molecule was synthesized through 9 steps including methyl esterification, reduction, Wittig reaction,  Sharpless catalytic asymmetric dihydroxylation, etc., with hyodeoxycholic acid as starting material, demosterol acetate as key intermediate, and  Sharpless catalytic asymmetric dihydroxylation as key step.       Results      Cerebrosterol was synthesized with the total yield of 52% and stereoselectivity of 97% de, and it was identified by mass spectrometry (MS), proton magnetic resonance spectroscopy (1HNMR), carbon magnetic resonance spectroscopy (13CNMR), infrared spectroscopy (IR), elemental analysis, etc.       Conclusion      The synthesis of cerebrosterol is characterized by high yield, high stereoselctivity, easy recrystallization and purification of each intermediate, and feasible scalability.

参考文献/References:

[1]Ercoli A, de-Ruggieri P. The constitution of cerebrosterol, a hydroxycholesterol isolated from horse brain[J]. J Am Chem Soc, 1953, 75(13): 3284. DOI: 10.1021/ja01109a515
[2]Di-Frisco S, De-Ruggieri P, Ercoli A. Isolation of cerebrosterol from human brain[J]. Boll Soc Ital Biol Sper, 1953, 29(7): 1351-1352.
[3]Dhar A K, Teng J I, Smith L L. Biosynthesis of cholest-5-ene-3beta, 24-diol (cerebrosterol) by bovine cerebral cortical microsomes[J]. J Neurochem, 1973, 21(1): 51-60. DOI: 10.1111/j.1471-4159.1973.tb04224.x
[4]Bjorkhem I, Cedazo-Minguez A, Leoni V, et al. Oxysterols and neurodegenerative diseases[J]. Mol Aspects Med, 2009, 30(3): 171-179. DOI: 10.1016/j.mam.2009.02.001
[5]Gosselet F, Saint-Pol J, Fenart L. Effects of oxysterols on the blood-brain barrier: implications for Alzheimer's disease[J]. Biochem Biophys Res Commun, 2014, 446(3): 687-691. DOI: 10.1016/j.bbrc.2013.11.059
[6]Schonknecht P, Lutjohann D, Pantel J, et al. Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer’s disease compared to healthy controls[J]. Neurosci Lett, 2002, 324(1): 83-85. DOI: 10.1016/S0304-3940(02)00164-7
[7]Bjorkhem I, Lovgren-Sandblom A, Leoni V, et al. Oxysterols and Parkinson's disease: evidence that levels of 24S-hydroxycholesterol in cerebrospinal fluid correlates with the duration of the disease[J]. Neurosci Lett, 2013, 555: 102-105. DOI: 10.1016/j.neulet.2013.09.003
[8]Leoni V, Long J D, Mills J A, et al. Plasma 24S-hydroxycholesterol correlation with markers of Huntington disease progression[J]. Neurobiol Dis, 2013, 55: 37-43. DOI: 10.1016/j.nbd.2013.03.013
[9]Leoni V, Caccia C. 24S-hydroxycholesterol in plasma: a marker of cholesterol turnover in neurodegenerative diseases[J]. Biochimie, 2013, 95(3): 595-612. DOI: 10.1016/j.biochi.2012.09.025
[10]Noguchi N, Saito Y, Urano Y. Diverse functions of 24(S)-hydroxycholesterol in the brain[J]. Biochem Biophys Res Commun, 2014, 446(3): 692-696. DOI: 10.1016/j.bbrc.2014.02.010
[11]Noguchi N, Urano Y, Takabe W, et al. New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death[J]. Free Radic Biol Med, 2015, 87: 366-372. DOI: 10.1016/j.freeradbiomed.2015.06.036
[12]Sodhi R K, Singh N. Liver X receptors: emerging therapeutic targets for Alzheimer’s disease[J]. Pharmacol Res, 2013, 72: 45-51. DOI: 10.1016/j.phrs.2013.03.008
[13]Viennois E, Pommier A J, Mouzat K, et al. Targeting liver X receptors in human health: deadlock or promising trail?[J]. Expert Opin Ther Targets, 2011, 15(2): 219-232. DOI: 10.1517/14728222.2011.547853
[14]Fourgeux C, Bron A, Acar N, et al. 24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma[J]. Chem Phys Lipids, 2011, 164(6): 496-499. DOI: 10.1016/j.chemphyslip.2011.04.006
[15]Castro-Torres I G, de-Jesus-Cardenas-Vazquez R, Velazquez-Gonzalez C, et al. Future therapeutic targets for the treatment and prevention of cholesterol gallstones[J]. Eur J Pharmacol, 2015, 765: 366-374. DOI: 10.1016/j.ejphar.2015.08.045
[16]Koizumi N, Morisaki M, Ikekawa N, et al. Absolute configurations of 24-hydroxycholesterol and related compounds[J]. Tetrahedron Letters, 1975, 16(26): 2203-2206.DOI: 10.1016/S0040-4039(00)72677-3
[17]Patrick K, Yoichi N, Bang L, et al. A stereoselective synthesis and a convenient synthesis of optically pure (24R)- and (24S)-24-hydroxycholesterols[J]. Bull Soc Chim Fr, 1983, Ⅱ: 189-194.
[18]Moriarty R M, Enache L A, Kinney W A, et al. Stereoselective synthesis of squalamine dessulfate[J]. Tetrahedron Letters, 1995, 36(29): 5139-5142. DOI: 10.1016/0040-4039(95)01011-6
[19]Koizumi N, Ishiguro M, Yasuda M, et al. Stereoselective introduction of hydroxy groups into the cholesterol side chain. Preparation of (24R)- and (24S)-24, 25-dihydroxy- and (25R)- and (25S)-25, 26-dihydroxyvitamin D3 by asymmetric synthesis[J]. J Chem Soc Perkin Trans I, 1983, 1401-1410. DOI: 10.1039/P19830001401
[20]Okamoto M, Tabe M, Fujii T, et al. Asymmetric isopropylation of steroidal 24-aldehydes for the synthesis of 24(R)-hydroxycholesterol[J].Tetrahedron: Asymmetry, 1995, 6(3): 767-778. DOI: 10.1016/0957-4166(95)00073-X
[21]Zhou X D, Zhou W S. A new highly stereoselective synthesis of cerebrosterol, an agonist of the nuclear receptor LXRs[J]. Tetrohedron, 2001, 57(39): 8291-8296. DOI: 10.1016/S0040-4020(01)00812-2
[22]Zhang D H, Zhou X D, Zhou W S. A Short and Highly Stereoselective Synthesis of Cerebrosterol[J]. Chinese Journal of Chemistry, 2002, 20(11): 1145-1148. DOI: 10.1002/cjoc.20020201104
[23]周向东, 郑辉, 周维善. 氧化甾醇受体(LXRs)配体的合成[J].科学通报, 2002, 47(24): 1868-1875. DOI: 10.3321/j.issn: 0023-074X.2002.24.007
[24]周向东, 周维善. 高立体选择性的合成24R, 25-和24S, 25-二羟基甾体化合物: 中国, CN1254716[P]. [2000-05-31].
[25]Kolb H C, VanNieuwenhze M S, Barry-Sharpless K. Catalytic Asymmetric Dihydroxylation[J]. Chem Rev, 1994, 94: 2483-2547. DOI: 10.1021/cr00032a009

相似文献/References:

[1]岳娟娟,周向东.海洋天然产物24-亚甲基胆固醇的高效合成[J].第三军医大学学报,2008,30(07):621.
 YUE Juan-juan,ZHOU Xiang-dong.Highly efficient synthesis of marine natural product,24-methylenecholesterol[J].J Third Mil Med Univ,2008,30(11):621.
[2]张琪,徐长荣,周向东.24-亚甲基-胆甾-3β,5α,6β-三醇的合成[J].第三军医大学学报,2009,31(10):906.
 ZHANG Qi,XU Chang-rong,ZHOU Xiang-dong.Synthesis of 24-methylenecholestan-3β,5α,6β-triol[J].J Third Mil Med Univ,2009,31(11):906.
[3]马婷,徐长荣,周向东.抗结核化合物24-酮帕格甾醇的设计合成[J].第三军医大学学报,2009,31(10):902.
 MA Ting,XU Chang-rong,ZHOU Xiang-dong.Design and synthesis of an antitubercular compound, 24-ketoarguesterol[J].J Third Mil Med Univ,2009,31(11):902.
[4]郑辉,徐长荣,周向东,等.新型LXRs配体——环氧胆烷酸甲酯一类物的化学合成[J].第三军医大学学报,2001,23(09):0.[doi:10.16016/j.1000-5404.2001.09.041 ]
 ZHENG Hui,XU Chang rong,ZHOU Xiang dong.[J].J Third Mil Med Univ,2001,23(11):0.[doi:10.16016/j.1000-5404.2001.09.041 ]

更新日期/Last Update: 2016-05-29