Bioactive C15 Acetogenins from the Red Alga Laurencia obtusa

Abstract

Species of the marine red algae Laurencia, are known to exhibit bromine and chlorine-containing C 15 nonterpenoid metabolites.1) Among these, are the unusual cyclic ethers, with a pentadec-3-en-1-yne carbon skeleton. The isolation of trans and cis-laurediols from L. nipponica indicated an evidence that, cyclic ether enynes were raised from linear C 15 acetylenic polyenes, through oxidation and cyclization processes.2) Several maneonenes (halogenated cyclic ether enyne) were isolated from the genus Laurencia, 3-9) the fundamental differences between them is either geometry (through C 3 -C 4 and/or C 12 -C 13 ) and/or stereochemical configuration (C 5 , C 6 and C 11 ).Apoptosis is a programmed form of cell death by which unwanted cells are removed from the body without causing inflammation.10) This contrasts with necrosis, which involves direct damage to cells and is associated with inflammation. 11)Apoptosis may be an alternative and better method by which cells, such as neutrophils, are removed from an inflamed site.12) An organism must also remove senescent, damaged, or abnormal cells that could interfere with organ function or develop into tumors.In the present investigations, we describe the isolation and structural elucidation of three new (cyclic ether enynes) 1, 2 and 3 along with one known isomer 4 5-7) obtained from the petroleum ether extract of the red alga L. obtusa. Results and DiscussionThe petroleum ether extract of the air dried algal material was fractionated on aluminum oxide column using a stepped gradient of hexane and ether. The fractions were examined by spot TLC chromatography and spray reagent methanolsulfuric acid (50%) to give four compounds (1-4).The spectral data of these four compounds (Table 1) showed their very close structural relationship and strongly suggested that they belong to the C 15 acetogenins. The structure of known (12E)-cis-maneonene-A (4) was established by comparing its physical and spectral data with literature. 5-7)Compound 1, was isolated as pale yellow oil. High resolution-electron ionization-mass spectra (HR-EI-MS) established the molecular formula C 15 H 16 BrClO 2 , implying 7 degrees of unsaturation. EI-MS exhibited a characteristic molecular-ion cluster at m/z 342/344/346 in a ratio 2 : 3 : 1, which clearly indicated the presence of one Br and one Cl atoms. The presence of acetylenic group, vinyl ether stretching, and two C-O functionalities were deduced from IR absorptions at n max 3286, 1687, 1126, and 1190 cm Ϫ1 , respectively. Hence, both oxygen atoms could be involved in ether links. The 13 C-NMR and distortionless enhancement by polarization transfer (DEPT) experiments allowed the determination of 1 methyl, 2 methylene, 9 methine and 3 quaternary carbon atoms. Moreover, 13 C-NMR and heteronuclear single quantum coherence (HSQC) spectra displayed resonance for four carbons bearing oxygen, three of these were demonstrated by the signals at d C 78.2, 79.4, and 82.9; while the fourth is of vinyl ether carbon at d C 152.0.The presence of a terminal conjugate...

Halogenated Organic Molecules of Rhodomelaceae Origin: Chemistry and Biology

“…The first examples of maneonene derivatives were cis-maneonenes A (551) and B (552), and trans-maneonene B (553) (Figure 46), which were isolated from a green variety of L. nidif ica collected off the south coast of Oahu, Hawaii. 344,345 Recently, (12E)-cis-maneonene E (555) was isolated from two Laurencia species, L. papillosa 347 and L. obtusa, 348 and was reported twice by the same group in 2011. 347,348 Confusingly, a different configuration at C 6 was described in the reports, although the assignment in the latter report seems more reasonable.…”

“…344,345 Recently, (12E)-cis-maneonene E (555) was isolated from two Laurencia species, L. papillosa 347 and L. obtusa, 348 and was reported twice by the same group in 2011. 347,348 Confusingly, a different configuration at C 6 was described in the reports, although the assignment in the latter report seems more reasonable. 348 As for the isomaneonene class, the only three ACGs of this type reported so far are isomaneonenes A (560) and B (561) from a Hawaiian collection of L. nidifica 345,346 and the C 5 -isomer of 560, lembyne B (562), from an unidentified Malaysian Laurencia species (Figure 47).…”

“…In 1990, Shirahama's group accomplished the first total synthesis of (+)-thyrsiferol (347), (+)-venustatriol (348), and (+)-thyrsiferyl 23-acetate (349) in a stereoselective manner via "Strategy I" (Scheme 5). 448−450 The processes for these syntheses included (1) construction of the BC ring system with a C 1 −C 6 carbon unit, (2) elongation of the C 17 −C 24 carbon side-chain, (3) formation of the D ring through stereoselective epoxidation of the 4-en-1-ol system and successive cyclization, and finally, (4) construction of the A ring by bromonium ion-induced cyclization of the 4-en-ol system.…”

“…85 The crude extract of L. venusta displayed significant activity against HSV-1 and vesicular stomatitis virus (VSV). Activity-guided fractionation led to the separation of the active components, which included thyrsiferol (347), venustatriol (348), and thyrsiferyl-23 acetate (349). 233 8.1.5.…”

“…Recently, the bromoditerpene neorogioltriol (344) was reported to possess analgesic and in vitro and in vivo anti-inflammatory activities, 229,522 while acetogenins (12E)-cismaneonene E (555) and (12Z)-cis-maneonene D (557) were found to have potential to regulate programmed death in the initiation and propagation of inflammatory responses. 348 Several bromophenols including 600, 601, 649−651, and 705 ( Figure 57) isolated from Odonthalia corymbifera were demonstrated to possess potent inhibitory activity against isocitrate lyase (ICL), a key enzyme in the glyoxylate cycle, as well as in the rice fungal pathogen Magnaporthe grisea. 523 In addition, as ICL inhibitors, these compounds may be promising candidates for crop protection, particularly to protect rice plants against M. grisea.…”