Cyclopentenone Derivatives Research Articles

Myrothenones A and B, Cyclopentenone Derivatives with Tyrosinase Inhibitory Activity from the Marine‐Derived Fungus Myrothecium sp.

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Taste‐Active Maillard Reaction Products: The “Tasty” World of Nonvolatile Maillard Reaction Products

This study was done to obtain greater insight into the structures and sensory activities of those tastants that are not present in foods per se, but are generated during food processing by Maillard-type reactions from carbohydrates and amino acids and thus remain unknown. In order to rank the tastants according to their relative taste impact and to identify the key tastants generated during thermal food processing, the so-called taste dilution analysis (TDA), which uses the human tongue as a biosensor for tastants, was applied to heated, intensely bitter tasting binary mixtures of glucose or xylose and proline or alanine, respectively. This screening technique led to the identification of previously unknown taste compounds, among which intensely bitter tastants such as quinizolate and homoquinizolate, a pungent-tasting pyranopyranone, cyclopentenone derivatives exhibiting a physiological cooling effect, as well as a taste-enhancing pyridinium betaine named alapyridaine will be presented.

Heterocyclic Derivative Syntheses by Palladium-Catalyzed Oxidative Cyclization−Alkoxycarbonylation of Substituted γ-Oxoalkynes

4-Yn-1-ones containing different substituents, prop-2-ynyl alpha-ketoesters, and prop-2-ynyl alpha-ketoamides have been caused to react catalytically under oxidative carbonylation conditions to give tetrahydrofuran, dioxolane and oxazoline, dihydropyridinone, and tetrahydropyridinedione derivatives in satisfactory yields. Reactions were carried out in MeOH or MeCN/MeOH mixtures at 65-100 degrees C in the presence of catalytic amounts of PdI(2) in conjunction with KI under 32 bar (at 25 degrees C) of a 3:1 mixture of CO and air. Anti and syn 5-exo-dig cyclization modes account for the formation of different products. It has been found that cyclopentenone, dihydropyridinone, and tetrahydropyridinedione derivatives, formed when the reaction is carried out at higher temperature and for a longer time, can also be selectively obtained through an acid treatment of tetrahydrofuran and oxazoline derivatives involving an unusual rearrangement. The structures of 6-methoxy-2,2-dimethyl-3-oxo-5-phenyl-2,3-dihydropyridine-4-carboxylic acid methyl ester and 2,2,5-trimethyl-3,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid methyl ester have been confirmed by X-ray diffraction analysis.

The Multicomponent Reaction of Dimethoxycarbene, Dimethyl Butynedioate and Electrophilic Styrenes: An Unprecedented Synthesis of Highly Substituted Cyclopentenone Acetals.

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A Pauson–Khand Approach to New Carbocyclic Nucleoside Analogs

AbstractThe synthesis of three new carbocyclic nucleoside analogs (CNAs) with the nucleobase attached to a 3′‐hydroxymethylcyclopent‐2′‐en‐1′‐yl scaffold is reported. A variety of symmetric dienynes (propargylic acetals of type 11) were used as substrates in a cobalt‐mediated Pauson–Khand (PK) reaction to give bicyclic cyclopentenone derivatives of type rac‐12 with high diastereoselectivity. These compounds are valuable building blocks for the synthesis of structurally diverse CNAs with a high biological potential as apoptosis‐inducing agents. Starting from the PK product rac‐12a, the synthesis of 4′‐trialkylsilyloxyethyl‐substituted nucleosides rac‐18 and rac‐19 (with 5‐bromouracil and 6‐chloropurine as a nucleo‐base, respectively) was accomplished in seven steps (28 % and 37 % overall yield). The regio‐ and diastereoselective nucleobase (NB) introduction was achieved by Pd0‐catalyzed allylic substitution. Starting from the PK product rac‐12e, the 2′‐phenyl‐4′‐trialkylsilyloxymethyl‐substituted CNA rac‐17 was prepared (6 steps, 29 % yield)by exploitingan alternative protocol — a Mitsunobu reaction — for the NB introduction. The key intermediates 12a and 12e were obtained in virtually enantiopure form by kinetic resolution by means of oxazaborolidine‐catalyzed borane reduction (CBS reduction) in the presence of a (R)‐diphenylprolinol‐derived B‐methyl oxazaborolidine catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Synthesis of 5′‐Substituted Fluoro‐neplanocin A Analogues: Importance of a Hydrogen Bonding Donor at 5′‐Position for the Inhibitory Activity of S‐Adenosylhomocysteine Hydrolase.

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Copper‐Catalyzed Dimerization of Chromium Fischer Carbene Complexes: Synthesis of Dialkoxytrienes and Their Nazarov‐Type Cyclization to 2‐Alkoxy‐2‐cyclopentenones.

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Myrothenones A and B, Cyclopentenone Derivatives with Tyrosinase Inhibitory Activity from the Marine-Derived Fungus Myrothecium sp.

New 3-amino-5-ethenylcyclopentenones, myrothenones A (4) and B (5), were isolated together with known 6-n-pentyl-alpha-pyrone (1), trichodenone A (2), and cyclonerodiol (3) from the marine algicolous fungus of genus of Myrothecium. The structure and absolute stereochemistry of the new compounds were established by spectral interpretation and X-ray analysis. Compounds 1 and 4 exhibited a tyrosinase inhibitory activity with IC(50) value of 0.8 and 6.6 muM, respectively, which are more active than kojic acid (IC(50), 7.7 muM) currently being used as a functional personal-care compound.

Cyclopentenones from a Novel [4+1]Cocyclization of Methylenecyclopropanes with Fischer Carbenechromium Complexes

Fischer carbenechromium complexes react with methylenecyclopropanes and bicyclopropylidene in an unprecedented manner. All four carbon atoms of the methylenecyclopropane moiety along with carbon monoxide are incorporated with the formation of three new C-C σ-bonds to give substituted cyclopentenone derivatives in moderate (33-58% for methylenecyclopropanes) to good yields (65-72% for bicyclopropylidene).

Structural manifestations of the cheletropic reaction

Examination of selected cyclopentenone derivatives which are fixed into the boat conformation reveals structural deviations from "normal" C-C(O) and C=O bond distances consistent with the early stages of the cheletropic extrusion of carbon monoxide.

The multicomponent reaction of dimethoxycarbene, dimethyl butynedioate and electrophilic styrenes: an unprecedented synthesis of highly substituted cyclopentenone acetals

The zwitterionic species generated by the addition of dimethoxycarbene to dimethyl butynedioate is trapped by arylidenemalononitrile to yield cyclopentenone derivatives.

Triphenylphosphine-mediated synthesis of 5-oxo-2,5-dihydrofurans through the reaction of dialkyl acetylenedicarboxylates and butane-2,3-dione

Dimethyl or diethyl acetylenedicarboxylates undergo smooth reactions with butane-2,3-dione in the presence of triphenylphosphine to yield highly functionalised 5-oxo-2,5-dihydrofurans; using di-t-butyl acetylenedicarboxylate affords a cyclopentenone derivative.

Design of 2-cyclopentenone derivatives with enhanced NF-κB: DNA binding inhibitory properties

In this work we derived a series of new inhibitors for the association between nuclear factor kappa B (NF-κB) and the corresponding κB site in DNA. They were derived through optimization of the lead compound 2-cyclopentenone (CP), which corresponds to the reactive unit of natural product 15-Deoxy-Δ 12,14-prostaglandin J 2 (PGJ2). Both CP and PGJ2 possess demonstrated inhibitory efficiency for this and other biological important systems. We began by studying the docking of CP to NF-κB. Subsequently, a set of rational strategies were derived to insert substituents into CP which increase its association to NF-κB, in terms of both the affinity and the specificity. Molecular mechanics calculations have been performed to decide on the suitability of the substitutions, and to evaluate the energies of association with NF-κB. One of the important chemical properties of CP is that it is a weak electrophile, hence it selects attacking nucleophilic sites in proteins, rather than the nucleic acids. To assure that the designed compounds were not substantially more reactive than CP we performed high level density functional theory calculations. Important conclusions have been obtained concerning the optimization of this inhibitor; namely, a set of methodologies for rational drug design have been derived to enhance the affinity of the CP derivatives to NF-κB. The efficacy of these methodologies has been demonstrated by generating a set of substituted CPs, exhibiting increased affinity for NF-κB, and opening new ways to broaden the therapeutic applications of this class of drugs.

Synthesis of 5′-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5′-position for the inhibitory activity of S-adenosylhomocysteine hydrolase

Four 5′-substituted fluoro-neplanocin A analogues 1a– d were designed and synthesized, using cyclopentenone derivative 2 as a key intermediate. The inhibitory activity against SAH was in the following order: NH 2 > SH > F, N 3, indicating a hydrogen bonding donor such as OH or NH 2 was essential for inhibitory activity. All the final compounds showed much less decreased cytotoxicity in two cancer cell lines (Col2 and A549), implying that phosphorylation of the 5′-hydroxyl group of fluoro-neplanocin A is closely related to its high cytotoxicity.

Synthesis of Fluorinated Cyclopentenyladenine as Potent Inhibitor of S‐Adenosylhomocysteine Hydrolase.

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Copper-catalyzed dimerization of chromium Fischer carbene complexes: synthesis of dialkoxytrienes and their Nazarov-type cyclization to 2-alkoxy-2-cyclopentenones

Fischer carbene complexes 1 underwent a clean ligand dimerization reaction yielding functionalized olefins and trienes 4 in the presence of copper (I) catalysts. If treated with trifluoroacetic acid (TFA), trienes 4c, d, f undergo a cyclization process (Nazarov reaction) which furnishes cyclopentenone derivatives 6c, d, 7c, d and 8 in good yields. Finally, the Fischer aminocarbene 9 efficiently cyclodimerizes to the substituted arene 10 in the presence of CuBr.

Novel platinum-catalysed cascade reactions: cyclisation, ring expansion and 1,2-oxygen shift reaction of a camphor-derived diyne

2,3-Bis(ethynyl)-3-hydroxy-camphorsultam was converted in one step into a novel tetracyclic cyclopentenone derivative, in an unprecedented platinum-catalysed cascade reaction. In the course of this reaction, cyclisation of the alkynes takes place, together with a ring expansion of the camphor skeleton and 1,2-migration of an oxygen atom. The structure of the unexpected product was analysed in detail by one- and two-dimensional NMR spectroscopy, and validated with the help of quantum mechanical calculations (B3LYP/6-31G ∗∗ and B3LYP/6-31+G(2df)) of the IR vibrational frequencies and the 1H and 13C isotropic chemical shifts.

Palladium‐Catalyzed Tandem Oxidative Cyclization of 1‐Bromohexa‐1,5‐dien‐3‐ols: Easy Access to Cyclopentenones.

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New cytotoxic metabolites from a marine sponge Homaxinella sp.

Three new butenolides (1-3), a new cyclopentenone derivative (4), and a known alcohol (5) were isolated from a marine sponge Homaxinella sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR and MS analyses. The stereochemistry of the butenolides and cyclopentenone derivative was defined on the basis of optical rotation and CD spectroscopy. The compounds were tested for cytotoxicity against a panel of five human solid tumor cell lines and displayed marginal to significant activity.

CO Insertion Reaction of Zirconacyclopentadienes.

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