Cyclobutane Skeleton Research Articles

Supramolecular Control of Photocycloadditions in Solution: In Situ Stereoselective Synthesis and Release of Cyclobutanes.

A new class of supramolecular metallacycles capable of undergoing photochemical reactions and in situ release of cyclobutanes in solution is described. The molecular metallacycles were generated through coordination-driven self-assembly of dinuclear metal-carbene complexes as organometallic clips with olefin-functionalized bridging ligands. Photolysis of these molecular metallacycles in situ led to structural interconversion and release of the formed cyclobutane products with quantitative conversion. Further modifications of the obtained cyclobutanes provided a series of new species containing the cyclobutane skeleton.

Supramolecular Control of Photocycloadditions in Solution: In Situ Stereoselective Synthesis and Release of Cyclobutanes

AbstractA new class of supramolecular metallacycles capable of undergoing photochemical reactions and in situ release of cyclobutanes in solution is described. The molecular metallacycles were generated through coordination‐driven self‐assembly of dinuclear metal‐carbene complexes as organometallic clips with olefin‐functionalized bridging ligands. Photolysis of these molecular metallacycles in situ led to structural interconversion and release of the formed cyclobutane products with quantitative conversion. Further modifications of the obtained cyclobutanes provided a series of new species containing the cyclobutane skeleton.

Polyanthumin, a novel cyclobutane chalcone trimmer from Memecylon polyanthum

A novel unusual trimmer chalcone, polyanthumin (1), together with five known compounds myricetin 3-O-(3″-O-galloyl)-α-l-rhamnopyranoside (2), sulfuretin (3), fustin (4), gallic acid (5), and ethyl gallate (6), was isolated from the dry stems of Memecylon polyanthum H.L. Li. Among them, compound 1 is a new chalcone trimmer with a novel cyclobutane skeleton in nature. Compounds 3 and 4 are flavonoids carrying a single 7-OH in A ring, which provided the first example of these class flavonoids from the family Melastomataceae. In addition, the antitumor activities for 2–4 were reported for the first time in this study. The antitumor effects of the isolated compounds 1–6in vitro were assayed by the SRB method using human cancer K562 cells, with the inhibition rates ranging from 39.4% to 54.5% at 100 μg/ml. The IC50 values of compounds 1 and 3 for the inhibition of K562 cell proliferation were determined to be 45.4 and 30.5 μg/ml, respectively. To the best of our knowledge, compound 1 was the second sample as chalcone trimer. In addition, the antitumor activities for 2–4 were reported for the first time in this study.

Rigenolide A, a new secoiridoid glucoside with a cyclobutane skeleton, and three new acylated secoiridoid glucosides from Gentiana rigescens Franch

Rigenolide A (1), a new secoiridoid glucoside with a cyclobutane skeleton and three new acylated secoiridoid glucosides, 2′-(2,3-dihydroxybenzoyl)-gentiopicroside (2), 2′-(2,3-dihydroxybenzoyl)-swertiamarin (3), 3′-(2,3-dihydroxybenzoyl)-sweroside (4), along with two noriridoids (7 and 8) and two known secoiridoid glucosides (5 and 6), were isolated from Gentiana rigescens Franch. The structures of new compounds were elucidated by extensive spectroscopic analyses. The isolated compounds were evaluated for DPPH free-radical scavenging activity.

Phytochemical of Indonesian Macaranga and their Cytotoxic Properties Against P388 Cells

Plants as a source of bioactive chemicals have been known since very long time, and thus it is a rational strategy to develop phytochemical studies on the Indonesian plants and tested the isolated chemicals on a various biological systems. Since 1999, the author, as a part the Group of Natural Products Chemistry, Institut Teknologi Bandung, has actively wotk on a number of Indonesian plant families, including Lauraceae, Moraceae, Dipterocarpaceae, Zingiberaceae, and Euphorbiaceae, aiming to find new biologically active chemicals from nature. In this presentation, studies on Macaranga species (Euphorbiaceae) will be presented, hightlighting the results from six species of the genus, namely M. gigantea, M. lowii, M. pruinosa, M. recurvata, M. rhizinoides, and M. trichocarpa. Samples of the plants to be extracted were the leaves, and extraction was done either with acetone or methanol. Fractionation was carried out by vacuum liquid chromatography eluted by a gradient solvent system of n-hexaneEtOAc. Purification of the metabolites was done mainly with radial chromatography eluted with various solvent systems. Twenty seven flavonoid and stibene derivatives were isolated and identified, seventeen of which were new compounds. These compounds are substituted with isoprenyl, geranyl, farnesyl, and an iregular sesquiterpenyl group with a cyclobutane skeleton. In the presentation, several selected NMR spectra of the compounds will be described. On biological evaluation against murine leukemia P-388 cells by MTT assay these compounds showed varying cytotoxicities, with the highest active compounds was an isoprenylated dihydroflavanone isolated from M. recurvata. In conclusion, Macaranga is a unique source of flavonoid and stilbene derivatives, some of them have potential for biological activities. Keeping that Indonesia is one of the center of Macaranga’s diversity, pytochemical and biological research on this plant should be continued.

(+)-Camphor Derivative Induced Asymmetric [2 + 2] Photoaddition Reaction

An efficient approach to construct an enantiomerically pure cyclobutane skeleton by means of the chiral auxiliary induced [2 + 2] photoaddition reactions has been described. This asymmetric photoreaction exhibited high diastereoselectivity and provided the photoadducts in excellent yields.

Enantioselective synthesis of rumphellaone A via epoxy nitrile cyclization

The first enantioselective synthesis of rumphellaone A, a cytotoxic 4,5- seco-caryophyllane derivative incorporating a γ-lactone ring as its structural feature, has been achieved by using base-induced intramolecular cyclization of an epoxy nitrile intermediate to install its cyclobutane skeleton as well as three contiguous stereocenters as the key transformation.

A versatile synthetic approach to grandisol monoterpene pheromone

A versatile and efficient synthetic procedure for the grandisol pheromone library has been established. The key feature of our synthesis involves a versatile and highly regioselective Pd(0)-catalyzed intramolecular allylic alkylation for the key cyclobutane skeleton of grandisol. In this connection, the concise synthesis of (±)-grandisol as well as mechanism study of Pd(0)-catalyzed regioselective cyclization as a key reaction have also been accomplished.

Phenolic Derivatives with an Irregular Sesquiterpenyl Side Chain from Macaranga pruinosa

A stilbene and two flavonoid derivatives, macapruinosins A-C (1-3), together with two known flavonoids, papyriflavonol A and nymphaeol C, have been isolated from the acetone extract of the leaves of Macaranga pruinosa. The structures of these compounds were identified based on spectral data analysis. Compounds 1 and 2 are the first examples of natural compounds containing an irregular sesquiterpenyl side chain with a cyclobutane skeleton.

Correlation diagrams of stereoisograms for characterizing stereoisomers of cyclobutane derivatives

Correlation diagrams of stereoisomers are developed as a versatile device for discussing the stereoisomerism of cyclobutane derivatives. A cyclobutane skeleton belongs to an RS-stereoisomeric group, which is constructed by starting from the point group D4h in order to represent a global symmetry. Stereoisomers derived from the cyclobutane skeleton are treated by a main correlation diagram of stereoisograms under the action of the RS-stereoisomeric group. In order to discuss the local symmetry of each RS-stereogenic center, on the other hand, a promolecule is generated at each RS-stereogenic center, where the RS-stereoisomeric group for specifying the promolecule is constructed by starting from the point group Td. Such promolecules derived from respective stereoisomers are correlated to each other by using stereoisograms, which are further correlated to give a correlation diagram of stereoisograms. RS-stereodescriptors are discussed on the basis of such correlation diagrams of stereoisograms.

PtCl2-Catalyzed Rearrangement of Methylenecyclopropanes

Alkylidenecyclopropanes readily convert into cyclobutene derivatives on treatment with catalytic amounts of PtCl2. The reaction is strongly accelerated when performed under an atmosphere of CO (1 atm). The resulting cyclobutenes are isolated in good to excellent yields for substrates bearing aliphatic as well as aromatic substituents R on their olefinic site. If the substituent R, however, is a very electron-rich arene, the cyclobutenes initially formed react further to give dimeric products with a previously unknown 1,2,2a,7a-tetrahydrospiro[cyclobuta[a]indene-7,1'-cyclobutane skeleton. A mechanism accounting for these experimental observations as well as for a deuterium-labeling experiment is proposed which implies reactive intermediates at the nonclassical cation/carbene interface. Furthermore it is shown that the PtCl2-catalyzed cyclobutene formation can be geared with subsequent ring-opening/ring-closing metathesis (ROM/RCM) events. Finally, a convenient "one pot" method for the preparation of the alkylidenecyclopropane substrates used in this study is presented, which is based on a modified Julia-Kocienski olefination of aldehydes with readily available 1-tert-butyl-1H-tetrazol-5-yl-cyclopropyl sulfone under Barbier conditions.

Synthesis of Cyclobutane Serine Analogues

In this paper, we describe a thermal [2 + 2] cycloaddition involving 2-acylaminoacrylates as electron-poor acceptor alkenes, a reaction that involves a Michael-Dieckmann-type process. The reaction gives rise to a new substituted cyclobutane skeleton that can be transformed into amino acid derivatives. For example, a number of transformations were carried out to give the two pairs of stereoisomers of the 2-hydroxycyclobutane-alpha-amino acid serine analogue (c(4)Ser); compounds 22 and 23. This synthesis covers a gap in knowledge in the broad field of restricted amino acids.

General synthesis of methyl- and dimethyl -cyclobutanes from simple 1,3-diols by phase transfer catalysis

A general method is described for the preparation of methyl- and dimethyl-cyclobutanes from simple 1,3-diols. The key steps of the procedure are a phase transfer catalysed ring closure and the transformation of a carboxyl group to a methyl group. Phase transfer catalysis provides good yields in the synthesis of the cyclobutane skeleton.

Enantio- and Diastereo-Selective Synthesis of (+)-Grandisol

Abstract (+)-Grandisol, an insect pheromone having cyclobutane skeleton, is synthesized enantio- and diastereo-selectively. The key steps in the synthesis are the asymmetric [2+2] cycloaddition reaction catalyzed by a chiral titanium reagent and the diastereoselective conjugate addition reaction by the combined use of Me2CuLi and trimethylsilyl trifluoromethanesulfonate.