【作者】 郑文丽；

【导师】 付超；

【作者基本信息】 四川大学 ， 应用化学， 2003， 硕士

【摘要】 光学异构体在生物活性、毒性及代谢机理上都不相同，因此外消旋体的拆分极为重要。手性固定相（CSP）高效液相色谱（HPLC）法是达到这一目的有效手段。 本文主要对高效液相色谱中的Pirkle型手性固定相进行研究。根据Pirkle型手性固定相的化学结构特点和手性拆分机理设计了一种新型苊衍生的酰胺型手性物质5-十一烯酰胺基苊，该物质的合成以苊为原料，经苊环碳原子的酰化反应、酮的还原胺化、氮原子上的酰化反应制得。合成中考察各步反应的反应条件，优化条件以得到较高产率。 目前国内外的文献中，还没有关于用高效液相色谱分离5-十一烯酰胺基苊的报道。本实验用DNB-Leucine CSP的HPLC直接拆分5-十一烯酰胺基苊，考察了流动相的组成、流速、柱温对溶质在色谱柱中的保留时间和溶质间分离度的影响。得到了拆分因子为1.09的色谱条件，用于制备拆分时可以得到光学纯度很高的5-十一烯酰胺基苊，但是溶剂耗费量很大。我们发现拆分试剂R（-）四氢噻唑-2-硫酮-4-羧酸（简称R（-）TTCA）对5-乙胺基苊有拆分能力，得到的单一对映体进行酰化反应有可能得到光学纯的5-十一烯酰胺基苊。 通过实验确定了各步反应的最佳实验条件，得到了两个未见文献报道的新物质5-乙胺基苊和5-十一烯酰胺基苊。实验结果表明，拆分试剂R（-）TTCA对5-乙胺基苊具有很好的手性识别能力，经拆分得到S（-）-5-十一烯酰胺基苊，产率72％，[α]=41.0；R（-）-5-十一烯酰胺基苊，产率80％，[α]=-24.2。用拆分了的5-乙胺基苊与10-十一碳烯基酰氯反应得到R（-）-5-十一烯酰胺基苊的比旋光度为[α]D²⁰=-23.1，得到摘要s（+）一5一十一烯酞胺基危的比旋光度为[。]D20二+2 7.6。因此我们可以先用R（一）TTCA拆分得到具有一定光学纯度的5一十一烯酞胺基范，再用制备色谱拆分部分旋光的5一十一烯酞胺基危，这样即可以得到高光学纯度的产品又可以降低成本。更多还原

【Abstract】 The enantiomers of all chiral molecules have to be isolated and to be tested for its difference in bioactivity, toxicity and the mechanism of metabolizability. The separation of enantiomers by chromatography on chiral stationary phases (CSPs) has been recognized as being a powerful alternative to the more conventional approaches such as enantioselective synthesis and enzymatically catalyzed transformations.In this paper Pirkle’s chiral stationary phases is chiefly investigated. According to chem-structures and chiral resolution mechanism of Pirkle’s CSP, a novel chiral substance 5-(10-undecenethylamido)-acenaphthene derived from acenaphthene has been prepared. The synthetic approach to the 5-(10-undecene thylamido)acenaphthene is via acetylation reaction to the acenaphthyl ring, deoxi amine reaction to the ketone, acetylation reaction to the amidocyanogen. All reaction conditions were studied and the best one are chosen.There is, to date, no paper on HPLC resolution of 5-(10-undecenethylamido) acenap hthene In order to get the single enantiomers of 5-(10-undecenethylamido) acenaphthene, the enantiomers are directly separated by chromatography on chiral stationary phases. Chiral resolution coefficients are investigated in different mobile phases, flow rate and temperature and we got the HPLC conditions of a =1.09, which uaually furnishes both enantiomers in high optical purity, but need much solvent. So we found a novel resolution reagent R-Thiazolidine-2-thione-4-carboxylic acid to separate 5-ethylaminoacenaphthene, which could provide better results.In experiments the scheme of preparation and resolution 5-(10-undecene thylamido)-acenaphthene is ensured. Experimental observations indicated that the resolving agent R(-)-TTCA provides excellent chiral recognition to 5-ethylamino acenaphthene. We got S(-) -5-ethylaminoacenaphthene, yield 72%, [ a ] =41. 0 ; R (-) -5-ethylaminoacenaphthene, yield 80%, [ a ] =-24. 2 ; R (-) -5- (10-undecenethylamido)- acenaphthene, [ a ] D20=-23.1 , S(+) - 5 - (10-undecenethy lamido)-acenaphthene, [a] D20 = +27. 6 . So we synthesized and separated 5-ethylaminoacenaphthene with R-TTCA, then produced optical pure 5-(10-undecenethylamido)-acenaphthene, which reduced the cost of resolution in HPLC.更多还原