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Synthesis of Tetrahydro-β\beta-carboline Alkaloid

G. He and M. Christmann

Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, GER

As the nature product based drug discovery is still one of the best weapons for human to explore and design novel drugs and drug leadings, our research interest is triggered to develop a divergent and general method to acquire one or several nature product families. And, β\beta-carboline alkaloids are an important group of natural and synthetic indole alkaloids which all bear the common feature of a tricyclic pyrido[3,4-b]indole ring structure. They own various biological activities, such as intercalation into DNA, inhibition of CDK, topisomerase, and monoamine oxidase, and interaction with benzodiazepine receptors and 5-hydroxy serotonin receptors . Furthermore, these compounds possess a variety of potential druggability, for example reserpine is an antipsychotic, and antihypertensive drug that has been used for the control of high blood pressure an relief of psychotic symptoms for decades; ajmalicine is also an antihypertensive drug used in the treatment of high blood pressure, and its analogue–yohimbine is a drug used in veterinary medicine to reverse the effects of xylazine in dogs and deer. Besides these well-known drugs, there are also many β\beta-carboline alkaloids own excellent activity, which might be drug leadings, such as lavendamycin (antitumor) and manzamine A (antivirus) . In addition, β\beta-carboline hybridized with salicylic acid displayed potent antiproliferative activity . In summary, the β\beta-carboline skeleton is a promising fragment in both nature product based and artificial designed drug discovery. Therefore, it is crucial and meaningful to develop a divergent and efficient strategy to assemble the β\beta-carboline skeleton.