Study On The Synthesis And Antitumor Acitivity Of Marine β-carboline Alkaloids

Alkaloid is an important part of the secondary metabolites obtained in natural,widely distributed in nature, including various plants, animals (such as the Africanfrog), marine organisms, cyanobacteria, mushrooms, and even the human blood andtissues (including the human brain, cerebrospinal fluid, platelet, milk, urine, liver,kidney and lens). Marine natural products is an important source of compoundshaving anti-tumor activity, and β-carboline alkaloids are a large group of natural andsynthetic indole alkaloids with with different degrees of aromaticity. Thesecompounds are of great interest due to their diverse biological activities. Thesechemicals also demonstrated a broad spectrum of pharmacological propertiesincluding intercalate into DNA, sedative, anxiolytic, hypnotic, anticonvulsant,antitumor, antiviral, antiparasitic as well as antimicrobial activities. In this paper, wealso summarized the synthesis of β-carboline compounds, the most widely usedPictet-Spengler reaction and Bischler-Napieralski synthesis strategy. Compoundsextracted from natural products, amount and types are limited, and to solve theproblem of shortage of in-depth research and clinical application of drug source, needto total synthetic explore marine alkaloid class of β-carboline marinacarbolines A-D,trying to find an effective synthesis route. Need to to fully synthetic explore the β-carboline class marine alkaloid, trying to find effective synthetic routes.This paper designed and completed cheap and easy routs to synthetic targetcompound marine natural product marinacarbolines A-D extracted fromactinomycetes and natural product tunicoides E isolated from the roots ofPsammosilent unicoides, using inexpensive and easily obtained tryptophan, indole,pyruvaldehyde,2-Phenylethylamine,2-(p-methoxyphenyl)ethylamine,4-Hydroxy-phenethylamine amine as the starting material. Using one-potPictet-Spengler reaction constructed aromatized β-carboline ring, simplifying thesynthesis step.2-Phenylethylamine,2-(p-methoxyphenyl)ethylamine,4-Hydroxy-phenethylamine and tryptamine have different properties, so differentmethods the esteramine exchange and preparing the acid chloride were used toconnect the amide bond, then the natural products were synthesized. All of the targetcompounds, their structures have been confirmed by nuclear magnetic resonance (1HNMR and13C NMR) and mass spectrometry (HRMS), providing a material basis forscreening and further developing of drug.The inhibition activity of Marinacarbolines A-D and compound7on the growthof A549cells, H1299cells has been tested and all of the compounds show moderateactivity. The derivates of3-formyl substituted β-carboline worth further research.Using computer-aided drug design and other means to study carbolinecompounds docking with tubulin, found marinacarbolines A and marinacarbolines Dbinding to tubulin binding sites consistent with colchicine. This predictions thesecompounds have tubulin inhibitory activity, for finding marine natural product torepalce colchicine provided.