Synthesis And Antitumor Evaluation Of The Natural Marine Allenic Compounds

It was reported that naturally occurring marine allenes usually exhibited impressive activities as antiviral agents, antitumor agent or enzyme inhibitors. Inspired by the intriguing biological activities of many allenic natural products, the natural marine allenic compounds which isolated from marine fungi xyllaria #2508 together with designed analogs were synthesized and the relationship between structures and antitumor activity in vitro were studied.Firstly, the progress in isolation, structures, synthesis and pharmaceuticals of current natural allenic compounds were reviewed in this paper. The preliminary biological tests showed that five marine natural allenic aromatic ether compound (2c, 2f, 3a, 3b, 3c) which isolated from marine fungal xyllaria #2508 by us is of certain antitumor activities in vitro. Therefore, we took them as primary research targets and used 2-propynol as starting material via mannich reaction, reduction, bromination, condensation, williamson reaction etc to synthesize the 12 allenic aromatic ethers 2a-2h, 2j, 3a-3c (see structure model: 2 and 3) which also included the total synthesis of six natural allenic compounds. The method possessed several advantagtes: synthetic routes were simple, reaction conditions were mild and yield was satisfied. All these compounds were charactered by IR, ¹H NMR, ¹³C NMR, MS, X-Ray and elemental analysis. Finally, the key-step to the successful synthesis of the target molecular was discussed and also the spectra were analyzed.The research on the relationship of structure-activity of 2a-2h, 2j, 3a-3c showed that all target compounds demonstrated antitumor activities against KB and KBv200 cells, ranging from weak to strong activities. We also found that the allenic moiety was the key to the target allenic compound 2 and 3 series to generate antitumor activity in contrast to the phenol 1 series.