Study On The Synthesis And Activity Of Anti-tumor Indole Alkaloid Calothrixin B And Its Derivatives

Objective:The anti-tumor indole alkaloid calothrixin B and its derivatives were synthesized using quinolino[4,3-b]-carbazole alkaloids as the mother nucleus,and the activity of its derivatives was studied,and a new anti-tumor indole alkaloid calothrixin was developed.The total synthesis method of B;the synthesis and activity research of new compounds around quino[4,3-b]carbazole alkaloids,in order to obtain new tumor active compounds.Methods:The five-ring skeleton was constructed by Baylis-Hillman /6πelectrocyclization/dehydroaromatization,the resulting lactam was reduced,and then the characteristic indolophenanthridine skeleton was obtained by oxidation.The intermediate was sub Jected to a highly regioselective Direct oxidation produces the final product calothrixin B with a higher yield of 91%.Through Diels-Alder cyclization/dehydroaromatization,a five-ring skeleton with a yield of 96% was constructed,the lactam obtained was reduced,and then oxidized to obtain a characteristic alcohol with an indolophenanthridine skeleton.The intermediate was zoned Selective direct oxidation to obtain the final product calothrixin B and its derivative aldehyde,and then regioselective oxidation of its derivative aldehyde to obtain the final product calothrixin B.Through Diels-Alder cyclization,the pentacyclic skeleton of the unsaturated heterocyclic ring was obtained with a yield of66%.The lactam obtained was reduced and then oxidized to obtain the methylphenanthridine skeleton.The intermediate was regioselectively oxidized to obtain the final product calothrixin B.The quinolino [4,3-b] carbazole alkaloid was introduced by hydrolysis and amine condensation to introduce a variety of amino side chains and Mannich reaction to introduce different amino side chains at the ortho position of the hydroxyl group to obtain the compound,and used The MTT method was used to test the cell proliferation activity of the synthetic compounds.Results:We have developed three methods for fully synthesizing the anti-tumor indole alkaloid calothrixin B.The research method has successfully obtained 13quinolino[4,3-b]carbazole alkaloids as the core indole alkaloids and successfully synthesized them.35 quino[4,3-b]carbazole alkaloids with anti-tumor activity have been developedConclusions:This paper successfully designed three economical,short and efficient new methods for the synthesis of tumor indole alkaloid calothrixin B and synthesized 35quino[4,3-b]carbazole alkaloids with anti-tumor activity.