The Synthesis Of [2-Amino-6-(3-(Benzyloxy)Phenoxy/Phenylthio)-1,2,3,4-Tetrahydro-Naphthalen-2-yl]Methanoi

The immune system is a special system，which can identify and exclude aliensubstances in the body，it is composed of natural immune system (non-specific immunesystem) and acquired immune system (specific immune system). The three functions ofhuman immune system are realized by the immune response，and immunosuppressive agentis a kind of the drug by influencing immune response，inhibiting immune function andtreating the diseases. In the clinic, immunosuppressive agents can inhibit various of adverseimmune reactions in organ transplant rejection and autoimmune diseases. However，immunosuppressive therapy mostly need lifelong medication，so there will be a lot of seriousadverse reactions from inhibiting the non-specific immune system，which are the ordinaryproblems we encountered in the process of the immunosuppressive treatment，such as：induction of infection，low therapeutic index，induction of malignant tumors，renal toxicityand so on，so that its clinical application is largely restricted. Now humans are in the pursuitof immunosuppressive agents with a faster reaction and a less adverse reactions. Because ofthis，the development of new immunosuppressive agents is more imminent.With the development of immune pharmacology and immune biology，some newimmunosuppressants appear. FTY-720was synthesized by Professor Fujita in1995withYoshitomi Pharmaceutical Company and become a brandnew immunosuppressant. Thechemical name is called2-amino-2-[2-(4-octyl-phenyl)ethyl]-1,3-propanediol hydrochloride.In a short time，the drug showed significant immunosuppressive effects and played a uniquerole in the clinic. The immunosuppressive effects of FTY-720is based on two factors，whichare different from the current immunosuppressants. It can reduce the number of B and Tlymphocytes in the peripheral blood, thereby weakening the attack on the graft. The decreasein peripheral blood lymphocyte will "homing" in the lymph nodes and intestinal lymph nodeset，which will not affect the NK cells、granulocyte and monocyte function. FTY-720couldaffect chemokine functions，decreasing the access number of T and B cells to transplantationby70%to80%, therefore，Xenotransplantation could significantly prolong the survivaltime，which prevent the occurrence of acute rejection and reverse the occurred rejection. The birth of FTY-720led to many scientists,s thinking. Basing on the structure-activityrelationship of ISP-1and FTY-720, we designed and synthesized a series of compoundsnamed FC. The synthetic route of the molecules (FC-022and FC-028) discussed in thisarticle is based on inter-bromo phenylacetic acid as a raw material, after the cyclizationreaction，carbonyl protection and deprotection with ethylene glycol, Ullmann reaction,Bucherer-Berg’s reaction，we got the target compound. The key intermediates and targetcompound are identified by1H-NMR,13C-NMR, MS and IR.Synthesis results indicated that，in the synthesis process of the diaryl ethers molecules(Ullmann reaction)，2-tetralone is relatively unstable under alkaline conditions，such asK2CO3、Na2CO3or NaOH. So2-tetralone etherification reaction should be carried out aftercarbonyl protected and then deprotection to give target product. Although this routeincreases the reaction steps，but it has a high yield in production，and it is easy to operate.Inaddition, the end product into a salt can be used directly without the separation andpurification，because its polarity can not be easily separated，at the same time，it simplifiesthe experimental operations.In this article we designed and synthesized a2-tetralone derivatives, they contained agroup of amine and alcoholic hydroxyl，which is similar to the active groups of FTY-720.Above all, this article has provided a new mentality for the immunity inhibitor’s research anddevelopment.