| Pelorol,a bicyclic sesquiterpene isolated from sponge,is a natural Marine product that has shown promising activity against trypanosomes and malaria parasites.Through access to a vast amount of literature,found that the Marine natural products pelorol and its derivative with anti-tumor,antifungal,antiviral,very wide range of biological activity,such as due to the existence of unique and a wide range of biological activity,make the Marine natural products pelorol class of compounds got the attention of scientists widely,has become a research hotspot.However,the synthesis of pelorol and its derivatives reported at present requires the use of some dangerous drugs,which makes the application of the route greatly weakened.Based on various factors,it is necessary to develop a new synthetic route of Peorol and its derivatives.In this paper,based on the research progress at home and abroad and the organic chemistry mechanism,we designed and synthesized Pelorol Marine natural products,and designed and completed the synthesis of three series of derivatives.The research mainly includes the following two aspects:1.Studies on the synthesis of pelorol compounds from Marine natural products.In this paper,we studied the synthesis of natural product molecules pelorol compounds.After previous research on these compounds,we conducted inverse synthesis analysis on them.According to their structural characteristics,they were separated into two fragments:bicyclic sesquiterpene and aromatic ring.The bicyclic sesquiterpene part is the cheap and easily obtained vanillin lactone which is hydroxylated,oxidized by sodium periodate and reduced by lithium aluminum hydride to get vanillin,and then reacted with p-toluenesulfonyl hydrazide to get vanillin with terpenoid group.The aromatic ring is made from dimethyl ether by superiodination of dimethyl ether.The key skeleton compound was obtained by palladium-carbon coupling of the two base fragments,which was then reduced by hydrogen,closed by Fourier alkylation,brominated by NBS,converted to aldehyde group by DMF,and oxidized to carboxyl group.Finally,the derived parent compound of pelorol was obtained.The corresponding ester derivatives,thioester derivatives and amide derivatives were obtained by condensation of EDCI with DMAP as catalyst.2.For 15 pelorol compounds synthesized,including pelorol,anti-PI3K enzyme and anti-tumor cell proliferation activity tests were carried out.After the analysis of the activity test data,it was found that the derived pelorol compounds3-10 had the best inhibitory effect on PI3K enzyme and tumor cells.It was found that the inhibitory effect on human leukemia tumor cells（K562）was the best.In addition,compound 3-10 had a better inhibitory effect on PI3K enzyme(IC50=0.850±0.021μM)than the positive control PI3K enzyme inhibitor LY294002(IC50=1.27±0.014μM),indicating that this compound had a clear targeting effect on PI3K,as a potential anti-tumor candidate that can be further developed as a selective PI3K inhibitor. |
