Design, Synthesis And Charactered Of Trans-R,R-1,2-cyclohexanediamine Cyclodextrin Conjugate Derivatives

Platinum-based anticancer drugs have become one of the most widely used anti-tumor drugs because of its unique mechanism of action and broad spectrum, but no targeting, side effects, drug resistance and other issues have become obstacles limiting its clinical application.Supramolecular chemistry delivery systems which have good safety and low toxicity were concerned by people in recent years. Supramolecular macrocycles-platinum complexes could enhance the water solubility, stability and safety of normal platinum drugs and it has became a hot research direction of developing new platinum-based anticancer drugs.Cyclodextrin as the second generation of supermolecular macrocycles, have been widely used in the construction and synthetic of new drugs. The mechanism of novel drug delivery system formed by platinum-based drugs and supramolecular macrocycles is different from classic platinum drugs in anti-cancer and cell uptake. It will be more effective in treatment of drug resistance tumor and the targeted transport capacity of macrocyclic compounds could reduce the side effects of platinum-based anticancer drugs.This article has focused on the synthesis of mono substitute beita-cyclodetrins derivates conjugate with trans-R,R-1,2-diaminocyclohexane, it will be used as the non-living group of platinum anti-cancer drugs in order to solve the problem of classic platinum drugs in clinic treatment. In addition, we expand the synthesis of6-OTs-CD to industrial production and try to use L/D-Dihydroxysuccinic acid to split the mix1,2-diaminocyclohexane.The major contents are as follow:1.6-OTs-CD was prepared and the synthesis process was expanded to industrial production, the structure of products were charactered by1H NMR spectroscopy.2. the L/D-Dihydroxysuccinic acid were used for chemical resolution of mixed 1,2-cyclohexane and trans-R,R-1,2-cyclohexane, trans-S,S-l,2-cyclohexane and cis-1,2-cyclohexane were separated. The structure of products were detemind by metling test and rotation photometry.3. we prepared several kinds of mono-substitute cyclodextrins derivatives:6-dach-CD,6-Gly-CD,6-Suc-CD,6-dach-Gly-Cd and6-dach-Suc-CD. All the products were charactered by1H NMR spectroscopy and mass spectroscopy.4.6-dach-CD-Ptl2were prepared and the product were charactered by1H NMR spectroscopy and mass spectroscopy.