Research On Secondary Metabolites From Two Marine-derived Actinomycetes

The ocean accounts for about 71%of the surface of the earth.It has abundant resources.Its environment is characterized by high salt,high pressure.low oxygen,low temperature and oligotrophy.The special growth environment and the unique metabolic methods may make the marine microorganisms produce structurally distinct active compounds that different from the compounds on the land.Marine actinomycetes are a class of Gram-positive bacterias that produce novel secondary metabolites with a variety of biological activities.Their secondary metabolites mainly include peptides,macrolides,nitrogen heterocycles,polyketones,terpenoids,steroids and other structures.This paper mainly includes three parts:literature review of new natural products of marine actinomycetes,screening of seven marine actinomycetes strains and study of secondary metabolites of two marine actinomycetes.seven marine actinomycetes were screened.With the guide of TLC,HPLC,NMR and LC-MS,we selected two marine actinomycetes {Streptomyces novaecaesareae and Actinomadura cremea),then we amplified,extracted and separated the secondary metabolites,performed their structural identification and tested the activity of the obtained monomer compounds.In this paper,the secondary metabolites of the marine actinomycete Actinomadura cremea were studied with Al medium.We got 20 compounds separated by Sephadex LH20 gel column,ODS column and semi-preparative liquid phase.The 17 compounds of them were identified by spectroscopy,physical constants and literature contrast.The 13 compounds are as follows:9β,11βepoxy-17β-hydroxy-16α-methyl-4-pregnadiene-3,20dione(1),16α-Methyl-4-pregnene-9β,11 β-oxido-17α,21-diol-3,20-dione(2),21(Acetyloxy)-9β,11β-epoxy-17α-hydroxy-16α-methylpregn-4-ene-3,20-dione(3),21(Acetyloxy)-17α-hydroxy-16α-methylpregna-4,9(11)-diene-3,20-dione(4),harman(5),Nacetyltryptamine(6),N-(2-(1H-indol-3-yl)ethyl)propionamide(7),cyclo-(L-Phe-L-Val)(8),cyclo(Z-Pro-L-Val)(9),cyclo-(L-Leu-Z-Val)(10),Cyclo(L-Ala-L-Val)(11),cyclo-(L-lle-LLeu)(12),cyclo-(L-Ala-L-Ile)(13),N-(4-hydroxyphenethyl)propionamide(14),Nacetyltyramine(15),N-phenethylacetamide(16),Valerolactam(17).The above compounds 1-8 and compounds 10-17 were isolated from the genus Actinomadura for the first time,and all the compounds were It was isolated for the first time from the actinomycete Actinomadura cremea.The compounds 1-4 are progesterone compounds,which can be used as key intermediates in the synthesis of steroid hormone drugs.The key intermediates of steroid hormones are obtained by microbial fermentation.It has the advantages of less reaction steps,high yield and less environmental pollution and it is of great significance for the development of steroid hormone drugs.The compounds 1-4 have been rarely reported from Marine actinomycetes.Therefore,Actinomadura cremea can be considered as a new strain for the preparation of steroid hormone intermediates.In this paper,the secondary metabolites of the marine actinomycete Streptomyces novaecaesareae were studied with A1 medium.We got 12 compounds separated by Sephadex LH-20 gel column.ODS column and semi-preparative liquid phase and identified by spectroscopy,physical constants and literature contrast.The 12 compounds are as follows:Cyclo-(L-4-Hypro-D-phe)(18),cyclo-(4-hydroxy-L-pro-L-phe)(19),cyclo(LPro-D-trans-Hyp)(20),cyclo(4-hydroxy-L-pro-L一leu)(21),cyclo-(L-Pro-L-Phe)(22),Cyclo-(L-leu-L-pro)(23),cyclo(D-Pro-L-Leu)(24),callyspongidipeptide A(25).N-(4oxopentyl)-acetamide(26),dibutylphthalate(27),Cyclo-(Ala-Phe)(28).Cyclo-(Z-ProGly)(29).The compounds 18-26,28-29 were ylide compounds.The compounds 18,20,24 and 25 contain D-configuration amino acids which are not common in nature.All compounds were isolated from Streptomyces novaecaesareae for the first time.