Structure and absolute stereochemistry of novel C15-halogenated acetogenins from the anaspidean mollusc Aplysia dactylomela

Three novel halogenated C₁₅-acetogenins, compounds 1-3, have been isolated, together with known metabolites, from a South China Sea collection of the anaspidean mollusc Aplysia dactylomela. The structures have been suggested by both NMR analysis and comparison with literature data. The structure of 1 was confirmed by a single crystal X-ray study, which also allowed the establishment of its absolute stereochemistry.     

Aplysiols A and B, squalene-derived polyethers from the mantle of the sea hare Aplysia dactylomela

Two novel triterpenoids, aplysiols A (5) and B (6), have been isolated, together with structurally related known metabolites, from a South China Sea collection of the anaspidean mollusc Aplysia dactylomela. The structures of 5 and 6 were determined mainly by spectroscopic NMR techniques. The absolute stereochemistry of compound 5 was deduced by Mosher's method as well as by biogenetical consideration, whereas the absolute stereochemistry of compound 6 was established also using an integrated NMR-QM (Quantum Mechanical) approach, based on the combination of ¹³C NMR chemical shifts and ^2,3J_C-H coupling constant DFT (density functional theory) calculations.     

New metabolites with antibacterial activity from the marine angiosperm Cymodocea nodosa

Four new metabolites (1-4) have been isolated from the organic extract of the seagrass Cymodocea nodosa, collected at the coastal area of Porto Germeno, in Attica Greece. Compounds 1 and 2 belong to the structural class of diarylheptanoids, which have been found only once before in marine organisms [Kontiza, I.; Vagias, C.; Jakupovic, J.; Moreau, D.; Roussakis, C.; Roussis, V. Tetrahedron Lett.2005, 46, 2845-2847]. Compound 3 is a new meroterpenoid, while compound 4, to the best of our knowledge, is the first briarane diterpene isolated from seaweeds, and only the second analog of this class with a tricyclic skeleton. Furthermore metabolite 4 is the first brominated briarane diterpene. The structures and the relative stereochemistry of the new natural products were established by spectral data analyses. The new metabolites were submitted for evaluation of their antibacterial activity against multidrug-resistant (MDR) pathogens including methicillin-resistant (MRSA) strains of Staphylococcus aureus, as well as the rapidly growing mycobacteria, Mycobacterium phlei, Mycobacterium smegmatis, and Mycobacterium fortuitum.     

Structure of homoplatensimide A: a potential key biosynthetic intermediate of platensimycin isolated from Streptomyces platensis

Platensimycin and platencin are novel natural product antibiotics that inhibit bacterial growth by inhibiting fatty acid biosynthesis enzymes FabF and FabF/FabH, respectively. Continued search for the natural congeners for structure activity relationship studies led to the isolation of a congener which possesses all of the twenty carbons of diterpenoid unit, a potential biosynthetic intermediate of platensic acid unit of platensimycin. Isolation, structure, and activity of homoplatensimide A and biosynthetic relationship to platensimycin have been described.     

Enantiodivergent synthesis of the key intermediate for a marine natural furanoterpene by chemoenzymatic process

A short chemoenzymatic route to both enantiomers of the key intermediate in the preparation of a marine natural furanoterpene was developed by employing a prochiral malonate derivative as a starting material.     

Bioactive marine metabolites VI. Structure elucidation of discodermin a,an antimicrobial peptide from the marine sponge Discodermia kiiensis

The structure of an antimicrobial peptide discodermin A isolated from the marine sponge Discodermia kiiensis has been elucidated as CHO-d-Ala-l-Phe-d-Pro-d-t-Leu-l-t-Leu-d-Trp-l-Arg-d-Cys(O₃H)-l-T$\text{hr-}\text{l}\text{-MeGln-}\text{d}\text{-Leu-}\text{l}\text{-Asn-}\text{l}\text{-Thr-Sar}$.     

Mycapolyols A-F, new cytotoxic metabolites of mixed biogenesis from the marine sponge Mycale izuensis

[structure: see text]. Mycapolyols A-F (1-6), six new unusual PKS/NRPS metabolites, were isolated from the marine sponge Mycale izuensis. The gross structures were elucidated by analysis of spectroscopic data, while the stereochemistry was established using chemical method and the universal NMR database.     

Extraction and isolation of linear alkylbenzene sulfonates and their intermediate metabolites from various marine organisms

A method has been developed for the determination of linear alkylbenzene sulfonates and its degradation intermediates (sulfophenylcarboxylic acids) from different marine organisms, which includes the stages of extraction and analysis by liquid chromatography with fluorescence detection. The extraction stage (Soxhlet and solid-phase extractions) was optimised by the selection of the appropriate solvent, minicolumns and different clean-up stages. Recoveries varied in the range from 80 to 104%, with a standard deviation between 1 and 9%. Detection limits were 15 ng g(-1) wet mass for undecylbezene sulfonate and 30 ng g(-1) wet mass for sulfophenylundecanoic acid using HPLC-fluorescence detection. The complete analytical method was successfully applied to different marine organisms from the Bay of Cadiz (SW Spain).     

Absolute stereostructures of cytotoxic metabolites, chaetomugilins A-C, produced by a Chaetomium species separated from a marine fish

Chaetomugilins A-C were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques, some chemical transformations, and an X-ray analysis. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Novel bioactive diterpenoid metabolites from tropical marine algae of the genus halimeda (Chlorophyta)

Four new diterpenoid metabolites, halimedarial (1), 3, 4 and 5, have been isolated from several species of the tropical green algae Halimeda (Udoteaceae). These new compounds show potent antimicrobial and cytotoxic properties in laboratory bioassays.     

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1-12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1-12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.     

Carbocyclic analogs of C-nucleosides: a key intermediate via a novel and efficient CC ring scission

Treatment of hydroxymethylene ketone $\text{6}$ with trimethylene dithiotosylate according to literature conditions,^3b led to the novel CC ring scission product $\text{7}$ in high yield; also, the hydroxide-initiated cleavage⁴ of $\text{1}$ gave the β-elimination product $\text{13}$ which underwent a highly stereospecific addition of diazomethane to provide $\text{15}$.     

Taxodal, a novel irregular abietane-type diterpene from the cones of Taxodium distichum

One novel irregular abietane-type diterpene denominated taxodal 1 was isolated from the cones of Taxodium distichum. The structure was estimated on the basis of NMR spectral data and confirmed by X-ray crystallographic analysis.     

Synthesis of triprenylated toluquinone and toluhydroquinone metabolites from a marine-derived Penicillium fungus

Two triprenylated toluquinone and toluhydroquinone marine fungal metabolites, 5-methyl-2-[(2′E,6′E)-3′,7′,11′-trimethyl-2′,6′,10′-dodecatrienyl]-2,5-cyclohexadiene-1,4-dione and 5-methyl-2-[(2′E,6′E)-3,7,11-trimethyl-2′,6′,10′-dodecatrienyl]-1,4-benzenediol, were synthesized in four and five steps, respectively, from 2-methyl-1,4-benzoquinone. The synthesis extends the applicability of the oxidative ether cleavage of hydroquinone dimethyl ethers with argentic oxide under acidic conditions to include the oxidative demethylation of polyprenylated-1,4-dimethoxy-toluhydroquinones with a quantitative survival of the oxidation- and acid-sensitive polyprenyl side chain.     

Effective tuning of the arene and alkanesulfinamides for highly enantioselective synthesis of (S)-4-chlorophenylphenylmethylamine, a key intermediate for antihistamic (S)-cetirizine

High diastereoselectivity (>94%) has been achieved in the phenylMgBr addition process to chlorophenyl aldimine derived from the new and sterically hindered triisopropylbenzene sulfinamide (TIPBSA) in the synthesis of a key intermediate of (S)-Cetirizine. Surprisingly, under the same reaction conditions, toluenesulfinamide derived chlorophenyl aldimine provided only 10% ee.     

Syntheses of two cytotoxic polyunsaturated pyrrole metabolites of the marine sponge Mycale micracanthoxea

Starting from eicosapentaenoic acid (EPA) the marine, naturally occurring, pyrrole derivatives, mycalazol 5 and mycalazal 2 have been synthesized. The Stille coupling reaction is a key step in the syntheses.     

Bioactive marine metabolites VII. Structures of discodermins B,C, and D,antimicrobial peptides from the marine sponge discodermia kiiensis

Isolation and structure elucidation of three peptide antibiotics, discodermins B, C, and D, from the marine sponge, Discodermia kiiensis, and the revised structure of discodermin A are described.     

Cell differentiation inducers from a marine sponge Biemna sp.

Two pyridoacridines closely related to the known isocystodamine were isolated from the marine sponge Biemna sp. together with isocystodamine. Their structures were determined on the basis of spectroscopic data. They induce the erythroid differentiation of human leukemia K562 cells with an ED₅₀ value of 5 nM each.     

New diastereomeric bis-sesquiterpenes from Hainan marine sponges Axinyssa variabilis and Lipastrotethya ana

Three unprecedented diastereoisomeric dimers, cis-dimer A (1), cis-dimer B (2) and trans-dimer C (3), exhibiting a bis-bisabolene skeleton, and a new sesquiterpene, dehydrotheonelline (4), their potential precursor, have been isolated from the South China Sea sponges Axinyssa variabilis and Lipastrotethya ana, along with known related sesquiterpenes. The structure of the novel molecules has been determined by extensive NMR spectral analysis.