Studies On The Synthesis And Chromatographic Performance Of Ferrocene-bonded New Pirkle Type Chiral Stationary Phases

The Pirkle type chiral stationary phase is one of the most extensive separation and analysis method in the chiral compounds’ resolution, which has a extremely wide application in chemical industry, pharmaceutical grade and pesticide. The research in column packing and separation mechanism of new Pirkle type CSP is the focus in the field of HPLC. The Pirkle type CSP has the determinate chemical structure and the common structure features, that is in the chiral part at least containing one of the following groups:polar hydrogen bond donor-receptor, in order to form polar groups to provide dipole interaction;π-base or π-acid aryl group; non-polar groups which have larg volume, in order to provide steric hindrance^Van der Waals role and configuration control function. This paper according to the research tendency of Pirkle type CSP, with reference to the structural features^separation mechanism and separation effect of the existing Pirkle type CSP, on the basis of the "three action points principle", designed for introducing metal organic compound ferrocene and biotin(a compound with multi-chiral parts) in the chiral stationary phase which can both provide strong π-π function and steric hindrance, in order to get good CSPs with innovative structures、specifical or universal separation effects. The study mainly includes the following respects:1、We chose several different kinds of composite condensing agents (DCC/DMAP, EEDQ, HOBt/EDCI), designed and synthesized several new chiral choice agents:The ferrocenecarboxylic acid and biotin derivatives of amino acid, that is N-ferrocenylformyl-L-alanine, N-ferrocenylformyl-L-phenylalanine, N-ferrocenylformyl-L-alanine-silane, N-ferrocenylformyl-L-phenyalanine and N-biotin acyl-L-phenyalanine. The above compounds were synthesized by several synthetic routes from which we selected the optimal one, then bonded the chiral compounds which had best specific rotation to the silica gel, and finally got new Pirkle type chiral stationary phase. Among those synthetic routes, we found the best way was making reaction in acetone/water(3:1.Vol). So that the product N-ferrocenylformyl-L-alanine could have the best specific rotation [a]D22=-33.2°(c=0.42, CH3OH).2、Designed two ways to bond silica gel:one was that the chiral compounds were firstly bonded to silane reagent, then cross-linked to silica gel; the other was that the chiral compounds were directly bonded to silane-silica gel. And we chose the best route in the end. After experiments, we found that the racemization of CSP was less in the latter, so we could make a preciction that the chiral separation performance of CSP prepared in the latter route is better.3、This paper used the Linear Solvation Energy Relationship(LSERs) Principle to evaluate the chromatographic performance of prepared new Pirkle type CSP, and discussed the reserve mechanism. On the prepared new Pirkle type CSP, we made baseline separations for alkyl benzene、halogeno benzene and a series of fused ring compounds. At the same time, we also made chiral separations for DL-phenylalanine, DL-tryptophan、DL-lipoic acid and clenbuterol enantiomers. The researches showed that there were strong π-π function、hydrophobic interaction and hydrogen bond function between the CSP and solutes, the CSP could effectively separate chiral compounds which have aromatic nucleus, with a beautiful chiral separation performance.