Study On The Secondary Metabolites From Penicillium HLKG-44 And The Synthesis And ESI-MS Analysis Of Phosphonodipeptides

Natural medicines are the primary access to drugs because of the wide range of biological activity.Microbes,being widely distributed throughout the biosphere,are important natural medicine sources for their rich and varied metabolic products.In this paper,a kind of penicillin with anti-tumor activity,which is isolated from the polluted area of Shaxi River,is studied.It is expected to obtain the secondary metabolites with anti-tumor activity through fermentation and separation from the penicillin HLKG-44.After fermentation the penicillin HLKG-44,we isolate and analyze its lipophilic constituents.Six conpounds were isolated by different isolation methods,then identification their chemical structure by NMR(¹H NMR,¹³C NMR,DEPT,HSQC, HMBC,etc.),MS,X-ray diffraction,infra-red,elemental analysis and other methods. The result of the anti-lung tumor cells A549 test showed that two of the compounds have better anti-tumor activity,50%inhibitory concentration(IC₅₀) were 0.02μg/mL and 18.9μg/mL respectively.Phosphorus play an important role not only in the metabolic and genetic process, but also in the origin,growth and all other chemical process of life.Previous study shows that phosphono-peptides,as one type of phospho compounds,can inhibit plant growth,the growth of cancer cells,anti-tobacco mosaic virus activity,and also a major inhibitor of serine protease(such as trypsin,chynotrupsin,thrombin,granzyme,uPA, and so on).These enzymes play an important role in the metabolism.Based on the study of such compounds,it is expected to provide an important basis for the drug development.A high production,low cost,simple and effective solvent-free synthesis method to obtain the phosphonic dipeptide precursor amino-phosphonate(APP) is proposed in this paper.Five kinds of new phospho-dipeptides are synthesized,their structure are identified.Through the spectrum of phosphorus(³¹P NMR),HPLC,crystal diffraction and circular dichroism analysis,selective of amino acids and APP reaction ability in the synthesis process is studied.The results showed that trptophane and proline show selectivity for one of the optical isomer of APP,while isoleucine,valine and phenylalanine show only partial selectivity.The fragment rule of ESI-MS for phospho-dipeptides was studied and two special rearrangements were werified.Research of the serine proteinase activity based on the model of pepsin showed that these compounds do not have significant inhibition activity.Inhibition of other types of serine protease will be studied further.