Studies On The Secondary Metabolites Of Marine Sponge Sarcotragus Sp. And Chinese Traditional Herbal Medicine Pyrrosia Petiolosa

Marine organisms, particularly sponges, have continued to provide a large group oflinear sesterterpenes. Quite a number of these compounds contain aβ-substituted furanring, some times a butenolide, in one terminal and a tetronic acid moiety in the otherterminal. The sesterterpenes were called Furanosesterterpene Tetronic Acids which isoften abbreviated to FTA. They always co-occur with degradation products includingC21, C22 and C24 norsesterterpenes. Sponges of genera Ircinia and Sarcotragus haveproduced a wide variety of FTAs. Studies showed FTAs possessed biological propertiessuch as antimicrobial, anti-inflammation, cytotoxicity, anti-predator, antifouling and etc.In the course of our search for biologically active lead compounds from marineorganisms, sponge Sarcotragus sp. collected at Soheuksan Island in southwestern Koreawhich showed promising activities was chemically studied. Brine shrimp lethality assayand proton NMR co-guided fractionation led to 4 active fractions which displayedcharacteristic FTA resonances in ¹H NMR spectra. 2 of the active and structurallyinteresting fractions were intensively studied. Solvent extraction, reversed phase flashchromatography, gel filtration on Sephadex LH 20, and semi-preparative HPLC wereemployed for separation and purification of the metabolites. Structurally elucidation of27 metabolites isolated from the methanol and dichloromethane extracts were aided by1D, 2D NMR, HRFABMS, IR, and UV. Some metabolites, although could notchromatographically resolved from their co-occuring positional isomers, werenevertheless characterized by spectroscopic analysis and chemical degradation. Theabsolute stereochemical features of some metabolites were pinned down by oxidationcleavage, PGME amides preparation, circular dichroic spectroscopy, and specific opticalrotation data comparison. 19 out of the 27 metabolites were new compounds.Compounds 5¹6 possessed an unprecedent succinate terminal which derived from abenzilic rearrangement of tetronic acid moiety. 2 metabolites, 18 and 19, featured a rare1, 4-dimethoxy furan moiety. In compounds 20～22, the furan moiety were oxygenatedinto butenolide which is unusual in FTAs. 23～27 were characterized as C21norsesterterpenes derived from the degradation of tetronic acid terminal.A review titled as "Progress on furanosesterterpenes tetronic acid" was provided. Related literature published up to February 2007 was reviewed and totally 33 referenceswere cited. The article does not try to illustrate all the FTAs reported but placedemphasis on the structural diversity of FTAs. It was organized in a different way fromthose generally adopted. The structure of a FTA was divided into 3 parts, namely, furanterminal (F part), terpene bridge (T part) and tetronic acid terminal (A part). All theFTAs were introduced by their variation in the 3 parts, respectively.The structural identification methods of FTAs were summarized based on 32references in Chapter Three. Similar with the review described above, extensive studieson the NMR data of the 3 parts of FTAs derivatives were carried out, which allows oneto judge different structure variation simply through ¹H NMR or/and ¹³ C NMR spectra.Stereochemistry determination was also discussed. Different chiral sites in FTA maylead to different spectroscopic or chemical strategies, including chemical degradation,PGME method, CD spectroscopy and optical rotation data analysis.The genus Pyrrosia comprises 110 species and over 50 of them have been found inChina. P. petiolosa, which occurs in most places of China, is one of the 3 main sources(P. petiolosa, P. lingua and P. sheareri) of the traditional Chinese herbal medicine"ShiWei" and has been traditionally used for the treatment of nephroptosis and asthma.As the review (up to April, 2007, 27 References cited) in Chapter Four showed, thespecies of this genus are generous in producing flavanoids, triterpenoids and phenolicacids. In order to find the bioactive components against nephroptosis, we isolated 31compounds from the ethanol extracts and the water extracts of this plant via repeatedcolumn chromatography on silica gel, polyamide, PTLC and recrystallization. Theywere identified as vanillic acid (33) , protocatechualdehude (34) , hydrocaffeic acid (35) ,caffeic acid (36) , 3,4-dihydroxylbenzalacetone (37) , 4-O-β-D-glucopyranosylcaffeic acid (38) , kaempferol (39) , kaempferol-3-O-β-D-glucopyranoside (40) ,amentoflavone (41) , (±) eriodictyol-7-O-β-D-glucuronide methyl ester (42) , (±)eriodictyol-7-O-β-D-glucuronide ethyl ester (43) , gossypetin-7-O-β-D-glucopyranoside (44) , kaempferol 3-O-β-D-glucopyranoside-7-O-α-L-arabinofuranoside (45) , gossypetin 7-O-β-D-glucopyranosyl (1→6) -α-L-arabinofuranoside (46) , chlorogenic acid (47) , chlorogenic acid methyl ester (48) ,chlorogenic acid ethyl ester (49) , 5-caffeoyl-1,3-quinide (50) , methyl 3, 4-di-O-caffeoyl quinate (51) , methyl 3, 5-di-O-caffeoyl quinate (52) , diploptene (53) , 24- methylene-9, 19-cyclolanost-3-yl acetate (54) , cycloeucalenol (55) ,α-tocopherol (56) ,β-sitosterol (57) , daucosterol (58) ,α-D-glucose (59) ,β-D-glucose (60) , sucrose (61) , ethyl a-D-fructofuranoside (62) and 5-hydroxymethylfurfural(63) by physico-chemical analysis and their ID, 2D NMR, MS, UV data.Among them, compound 45 was a new compound, and for the first time, the occurrenceof compound 35, 37, 38, 41, 49～52, 54～56, 62 in genus Pyrrosia were demonstrated.Compounds 33, 34, 36, 59, 60, 63 were newly found from this species.