The Synthesis Of [2-amino-7-(3-phenytmethoxy) Phenylthio-1,2,3,4-tetrahydro-naphthalen-2-yl]methanol

Immune inhibitors are a class of chemical or biological substances,which can alleviatethe tissue damage by inhibiting cellular and humoral immune responses. People had began todeepen the understanding of the immunosuppressant,scince1914when a single organiccompound benzene can cause immune suppression was reporeed. At present,theimmunosuppressant has become a hot topic,it has been applicating extensive in manyfields of cancer chemotherapy,organ transplantation,immune pathology and clinicalimmunology. However,the immunosuppressant is also facing some problems,most of themlack specificity,using long-term will not only reduce the body’s normal immune response,butalso cause the body to infection and induce tumors and so on. Therefore,it will be importantand difficult to development and research a immunosuppressant that specific,highefficiency and low toxicity.1994, Fujita who a Professor of Kyoto University found ISP-1from the activeingredients of Cordyceps.Structure is shown in Figure1:Figure1Structure of ISP-1The ISP-1has a significant immunosuppressive effects, he according to the basicprinciples of drug design to transformate structural of ISP-1, the carboxyl group in themolecule is replaced by hydroxymethyl, the molecule still has obviousimmunosuppressiveactivity. On the basis,they further optimize the structure in order to get stronger inhibitoryactivity than the ISP-1:FTY-720.The chemical name is2-amino-2-[2-(4-octyl-phenyl)ethyl]-1,3-propanediol hydrochloride. Structure is shown inFigure2:Figure2Structure of FTY-720This paper describes the immunosuppressive agents R&D status in recent years,esceptically FTY-720, include R&D status,domestic and foreigan chemicalsynthesis, structure-activity relationship. According to the structure-activity relationship ofFTY-720, we designed and synthesized α-amino alcohol derivatives with FTY-720similargroups.7-substituted2-tetralone as starting material, potassium cyanide and ammoniumcarbonate addition, Hein alkaline hydrolysis, α-amino acid restore,salt to get the targetmolecule. During the experiment, all intermediates and target molecules are confirmed by13C NMR,1H NMR, IR and MS. The synthesis route not only related to conventionalchemical reactions, but also several classical organic synthesis reaction, such as Ullmanncoupling reaction and the Bucherer-Berg’s synthsis. Ullmann coupling reaction is usingwidely to synthetic the Ether by using inexpensive and easy to get the copper reagent as acatalyst. The Bucherer-Berg’s synthsis method,simple operation,high yield,easy toimplement industrial production,is now used for the synthdsis of hydantion derivativeswidely.In this paper, in addition to the conventional synthesis of target molecules, we alsoconducted a preliminary study on the chiral synthesis of the target molecule. Because thetarget molecule contains a chiral carbon, resulting in the whole molecule is chiral. Takinginto account that there may be some differences in pharmacological activity between pairs ofenantiomers, we choose the chiral synthesis of target molecules in order to obtain pureoptically active substances. We have chosen S-(+)-mandelic acid to split free base of thedesign and synthesis of target molecule, pure optically active free base are got and then intoits salt. Eventually,we got the pure optically active target molecules. We do thepharmacological activity test of each pair enantiomers. The pharmacological experimentsshow that the target molecule has inhibition on the lymphocyte,especially levo, with morethan FTY-720inhibition of lymphocyte activity. Pharmacological activity of racemic targetmolecule is quite with FTY-720. This is consistent with FTY-720structure-activityrelationship. At the same time, it also laid the foundation for the development of newimmunosuppressive agents and chiral.