Dissertation > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry > Organic synthesis of Medicinal Chemistry

The Synthesis of Two (2-amino-6-substituted-1,2,3,4-Tetrahydro-naphthalen-2-yl) Methanol Compounds

Author WangWeiWei
Tutor WangEnSi
School Jilin University
Course Medicinal Chemistry
Keywords Immunosuppressant Amino Alcohol Synthesis Suzuki reaction
CLC R914.5
Type Master's thesis
Year 2012
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The immunosuppressants were a kind of im-munosuppressive drugs, that were widelyused in organ transplant rejection reaction and autoimmune disease. They play an importantrole in the clinical treatment. But at present most of the immunosuppressants that werecommonly used have strong side effects.They may induce infection and tumor so themedical workers are constantly committed to the development of new immunosuppressiveagents.Especially with the discovery of enzymes, receptors and the other new targets thatrelated to the immune function we have developed many kinds of specific newimmunosuppressants with high activity.In this paper,we introduced four kinds of new immunosuppressants according to theirdifferent targets and mechanismas. They are the inhibitors of dihydroorotate dehydrogenase,Janus kinase3and protein kinase C and sphingosine-1-phosphate agonists. FTY-720synthesized by Professor Fujita with Yoshitomi Pharmaceutical Company was a kind ofsphingosine-1-phosphate agonists. It has unique pharmacological characteristics, goodcurative effect and less toxic side effect than conventional immunosuppressants.It plays animportant role in the clinical treatment of many diseases. It is a promising immuno suppress-ant. furthermore it has a novel structure that can be used as lead compounds for furtherdevelopment of new immunosuppressive agents.According to the studies on structure-activity relationship of FTY-720and the researchexperience of new immunosuppressive agents FC in our laboratory, we designed andsynthesized two target compounds:[2-amino-6-phenyl-1,2,3,4-Tetrahydronaphthalen-2–yl]methanol and [2-amino-6-(6-methoxyhexyl)-1,2,3,4-Tetrahydronaphthalen-2-yl] methanol.The basing structure of the target compounds was tetralin, the2position was substitutedby hydroxymethyl and amino. They are in the same strain with the other2-amino-6-substituted-1,2,3,4-tetrahydro-2-naphthalene methanol and2-amino-7-substituted-1,2,3,4-tetrahydro-2-naphthalene methanol. They are useful for the further study of the compoundstructure-activity relationships and lay a good foundation for the development of newimmunosuppressants. This paper briefly introduces the synthesis method of organic boron reagent, α-aminoacid, palladium catalyzed C-C bond coupling and details the characteristics of Suzukireaction which is a classic C-C bond coupling method. Moreover I analyzes and summarizedvarious factors that influence the effect of the Suzuki reaction such as electrophiles, boricacid, alkali reagent, catalyst and reaction conditions. This provides a solid theoretical basisfor the improvement of methods in the experiment.The two target compounds were synthesized by6-bromo-2-tetralone as starting material,6-substituted-2-tetralone as intermediate and Suzuki reaction, Bucherer-Berg’s reaction,hydantoin hydrolysis and carbonyl reduction as key steps. The key intermediates and targetcompound are identified by1H-NMR,13C-NMR, MS and IR.

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