Bis-tetrahydrofuran Ring Research Articles

Marinoterpins A-C: Rare Linear Merosesterterpenoids from Marine-Derived Actinomycete Bacteria of the Family Streptomycetaceae.

The chemical examination of two undescribed marine actinobacteria has yielded three rare merosesterterpenoids, marinoterpins A–C (1–3, respectively). These compounds were isolated from the culture broth extracts of two marine-derived actinomycetes associated with the family Streptomycetaceae, (our strains were CNQ-253 and AJS-327). The structures of the new compounds were determined by extensive interpretation of 1D and 2D NMR, MS, and combined spectroscopic data. These compounds represent new chemical motifs, combining quinoline-N-oxides with a linear sesterterpenoid side chain. Additionally, consistent in all three metabolites is the rare occurrence of two five-ring ethers, which were derived from an apparent cyclization of methyl group carbons to adjacent hydroxy-bearing methylene groups in the sesterterpenoid side chain. Genome scanning of AJS-327 allowed for the identification of the marinoterpin (mrt) biosynthetic cluster, which consists of 16 open-reading frames that code for a sesterterpene pyrophosphate synthase, prenyltransferase, type II polyketide synthase, anthranilate:CoA-ligase, and several tailoring enzymes apparently responsible for installing the N-oxide and bis-tetrahydrofuran ring motifs.

A New Polyketide-Derived Metabolite with PTP1B Inhibitory Activity from the Endophytic Fungus Pestalotiopsis neglecta

A new polyketide-derived metabolite, named neglectine A, was isolated from cultures of the endophytic fungus Pestalotiopsis neglecta. Its structure was elucidated by analysis of 1D and 2D spectroscopic data as well as MS. Neglectine A possessed a rare bis-tetrahydrofuran ring system and showed moderate activities against SHP1, CDC25B, and PTP1B, with IC50 value of 17.1 μg/mL, 24.0 μg/mL, and 6.7 μg/mL, respectively. It is important to note that neglectine A has exhibited significant selectivity between PTP1B and CDC25B, LAR, SHP1, and SHP2. This is the first time that neglectine A is reported to have significant PTP1B inhibitory action.

Selective Acetogenins and Their Potential as Anticancer Agents.

The Kingdom Plantae has provided several successful drugs for the treatment of different diseases, including cancer, and continues to be a source of new possible therapeutic molecules. For example, the annonaceous acetogenins (AAs) are secondary metabolites found in the Annonaceae family, which are plants employed in traditional medicine for the treatment of cancer and various other diseases. These polyketides are inhibitors of Complex I in the respiratory chain of tumor cells, a process that is closely related to tumor metabolism, cell death, apoptosis, and autophagy. The goal of this review is to update readers on the role of the AAs as antitumor agents using in vitro and in vivo studies to demonstrate their importance in the area of oncology drug discovery. For this purpose, we performed a literature search in the PubMed scientific database using a range of keywords, including acetogenins and cancer, acetogenins antitumor activity, acetogenins and cytotoxicity, and acetogenins mechanism of action, among others. As a result, we found that the AAs are cytotoxic compounds that can induce apoptosis, cell cycle arrest, and autophagy in vitro, in addition to exhibiting tumor growth inhibition in vivo. The functional group related to their antineoplastic activity is suggested to be the mono or bis tetrahydrofuran ring accompanied by two or more hydroxy groups. The versatility of the AA bioactivity therefore renders them potential therapeutic agents for cancer treatment. It is therefore apparent that nature is worth further examination to aid in the discovery of more effective, accurate, and less harmful therapies in the fight against cancer.

Toxicity of squamocin on Aedes aegypti larvae, its predators and human cells.

The mosquito Aedes aegypti transmits a virus that causes diverse human diseases, and control of the vector is an important strategy to avoid disease propagation. Plants in the family Annonaceae are recognised as sources of molecules with uses in the medical and agriculture fields. Molecules of secondary metabolites of Annonaceae plants exhibit insecticidal potential against insect pests and vectors, especially acetogenins, showing high toxicity at low doses, which has encouraged research into producing new insecticide molecules. Herein, we identify an acetogenin from Annona mucosa seeds (chemical analysis) and provide the results of toxicity tests against larvae of A. aegypti (target insect) and its predators Culex bigoti and Toxorhynchites theobaldi (non-target insects) and cytotoxicity to human leukocytes. We identified squamocin (C37 H66 O7 ), a fatty acid with a bis-tetrahydrofuran ring. In A. aegypti, this compound caused behavioural disturbance before larval death and high mortality at low concentrations (LC50 = 0.01 µg mL-1 and LC90 = 0.11 µg mL-1 ). However, in predators and human leukocytes, squamocin showed no toxicity effect, indicating the selectivity of this molecule for non-target organisms. We identified squamocin from A. mucosa seeds, which exhibited lethal action against A. aegypti and showed selectivity for non-target insects and low cytotoxicity to human cells. © 2016 Society of Chemical Industry.

Studies directed towards the total synthesis of polyether antibiotic ionomycin: asymmetric synthesis of fragments C(24)–C(32) and C(1)–C(23)

A convergent and stereoselective approach for the synthesis of C1–C23 and C24–C32 segments of polyether antibiotic, ionomycin has been achieved. The key steps involved in this approach are the elaboration of two advanced fragments from a common precursor using enzymatic desymmetrization to create two methyl chiral centers, desymmetrization of the bicyclic olefin to introduce two methyl and two hydroxyl chiral centers, the use of Evans auxiliary to introduce another methyl group and the creation of four chiral centers in bis-tetrahydrofuran ring by Sharpless asymmetric epoxidation and the regioselective opening of epoxide with methyl sulphone. The coupling of C11–C16 with C17–C23 was achieved through a Julia-Kocienski olefination and directed Aldol reaction. Oxidation of C9 alcohol facilitates the coupling of C10–C23 with C1–C9.

Stereodivergent and Reiterative Synthesis of Bistetrahydrofuran Ring Cores of Annonaceous Acetogenins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chamuvarinin, an acetogenin bearing a tetrahydropyran ring from the roots of Uvaria chamae.

A new cytotoxic acetogenin, chamuvarinin (1), containing a tetrahydropyran ring with an adjacent bis-tetrahydrofuran ring, which corresponds to a novel carbon skeleton in this series, was isolated from the roots of Uvaria chamae, together with the previously reported acetogenins squamocin (2), desacetyluvaricin (3), and neoannonin (4). The structure determination of chamuvarinin (1) was based on extensive NMR studies and high-resolution mass spectral measurements. This new compound shows significant cytotoxicity toward the KB 3-1 cell line (IC50 = 8 x 10(-10) M). In addition, a biosynthetic relationship between 1 and 2 is briefly discussed.

Stereodivergent and reiterative synthesis of bistetrahydrofuran ring cores of annonaceous acetogenins.

Eight diastereoisomers of the bistetrahydrofuran ring cores of annonaceous acetogenins have been synthesized by asymmetric alkynylation of alpha-tetrahydrofuranic aldehydes and stereodivergent one-pot tetrahydrofuran (THF) ring formation. In all cases, the asymmetric alkynylation proceeded with very high diastereoselectivity to give eight kinds of optically pure THF cores. We also describe a comparison of the (1)H and (13)C NMR spectral data of the eight isomers and give full details of the THF ring construction.

New adjacent Bis-tetrahydrofuran Annonaceous acetogenins from Annona muricata.

Bioactivity-guided fractionation led to the isolation of two new Annonaceous acetogenins, annocatacin A ( 1). and annocatacin B ( 2). from the seeds and the leaves, respectively, of Annona muricata. Compounds 1 and 2 are the first examples where the adjacent bis-tetrahydrofuran ring system is located at C-15. The new structures were elucidated and characterized by spectral and chemical methods. Both Annonaceous acetogenins 1 and 2 showed significant in vitro cytotoxicity toward the human hepatoma cell lines, Hep G2 and 2,2,15, and were compared with the known adjacent bis-tetrahydrofuran acetogenins, neoannonin ( 3). desacetyluvaricin ( 4). bullatacin ( 5). asimicin ( 6). annoglaucin ( 7). squamocin ( 8). and rollimusin ( 9).

Hydrogen bonding control in the oxidative cyclisation of 1,5-dienes

The regioselective dihydroxylation of a series of functionalised polyenes is described. Under acidic conditions, the osmate ester derivatives obtained from oxidation with OsO4/TMEDA undergo an intramolecular cyclisation reaction forming functionalised tetrahydrofurans with high stereoselectivity and in good yield. The generality of this method is illustrated with an application to the synthesis of a bis-tetrahydrofuran ring system.

Three new adjacent bis-tetrahydrofuran acetogenins with four hydroxyl groups from Asimina triloba.

Three new adjacent bis-tetrahydrofuran ring Annonaceous acetogenins with four hydroxy groups, bullatetrocin (1), 10-hydroxyasimicin (2), and 10-hydroxytrilobacin (3), were isolated by activity-directed fractionation from the stem bark of Asimina triloba. Their structures were established on the basis of chemical and spectral evidence. The absolute stereochemistry at the C-10 hydroxy position was determined by converting 2 and 3 to their ketolactone isomers, 2,4-cis/trans 10-hydroxyasimicinones and 2,4-cis/trans 10-hydroxytrilobacinones, respectively. The bioactivities of the new compounds against brine shrimp larvae and six human solid-tumor cell lines are reported, and structure-activity relationships between trihydroxylated and tetrahydroxylated acetogenins are discussed. In addition to 1-3, gigantetrocin A, 2,4-cis/trans-gigantetrocin A-ones, annonacin, and annonacin A were also isolated for the first time from this species.

Strategy and Construction of the Backbone Bistetrahydrofuran System Towards Synthesis of Rollinicin

Abstract Rollinicin1 (I), uvaricin2 (II) and cherimoline3 (III), the new antitumour, antibiotic agents, isolated from renewable resources having bistetrahydrofuran ring system in the molecules, have been recently reported. Bates2 has postulated that uvaricin has been probably biosynthesised from 1,5,9-trienoic acid derivative. The central portion of I - III, a bistetrahydrofuran ring system, is apparently novel. This prompted us to develop a methodology for the construction of the central bistetrahydro-furan ring system (L) using acetylenic derivatives as the starting materials for the first time. In this communication, we report 4 its result.