Highly Oxygenated Cyclobutane Ring in Biomolecules: Insights into Structure and Activity

Chemical investigation of an alcoholic extract from the stem of Daphne papyracea ("Xuehuagou") led to the isolation of the tetracyclic sesquiterpenoid daphnepapytone A (1), containing a unique caged skeleton with a cyclobutane ring having three tetrasubstituted chirality centers. Also isolated were new guaiane sesquiterpenoids, namely, daphnepapytones B-H (2-8), and one 1,5-diphenylpentanone 2-hydroxy-5-oxo-daphneone (9), together with 26 known compounds. The cyclic metabolites share a 5-isoprenyl-hexahydroazulene-2(1H)-one skeleton with different substitution patterns and a bridged cyclobutane, oxetane, or tetrahydrofuran ring. The planar structures and relative configuration of the new compounds were elucidated on the basis of spectroscopic analysis aided by DFT 13C NMR calculations. The absolute configurations of 1-7 were determined by X-ray single-crystal diffraction or TDDFT-ECD calculations. Daphnepapytones A and C (1 and 3), 2-hydroxy-5-oxodaphneone (9), daphnenone (10), daphneone (11), and 3-methyldaphneolone (12) showed α-glycosidase inhibitory activity, with IC50 values of 159.0, 102.3, 139.3, 43.3, 145.0, and 126.1 μM, respectively.

The photocleavage reaction of dimer model compounds of photosensitive polyimides having cyclobutane rings in the main chain was studied. Efficient photocleavage was observed for the dimer models (CBAM2, CBAM4, and CBPM2) which had an electron‐donating aromatic substituent at the electron‐accepting imide group. On the other hand, the cleavage quantum yield was nearly zero for a dimer (CBCM2) which had a cyclohexane substituent instead of the aromatic ring. Solvent polarity effects on the cleavage quantum yield revealed that these dimers gave the largest photocleavage efficiency in medium‐polar solvents. The transient absorption band of the excited triplet of CBPM2 was effectively quenched by oxygen, whereas no oxygen quenching was observed for the cleavage quantum yield. This leads to the conclusion that the cyclobutane ring in the polyimide is photocleaved via the excited singlet intramolecular CT state.

1. An equation for gyration has been derived which accounts for the scatter of polarizability anisotropy. 2. A polarizability ellipsoid has been determined for the C=C double bond and the bonds that make up the cyclobutane ring.

The title compounds, 1-methyl-1-phenyl-3-[1-hydroxyimino-2succinimido) ethyl] cyclobutane, C17H20N2O3, (I), and 1-(3-methly-3phenylcyclobutyl)-2-morpholin-4-yl-ethanone oxime, C17H24N2O2, (II), crystallize in space group P21/c, [1]. Each compound contains a cyclobutane ring, an oxime group and a benzene ring [2]. The cyclobutane ring in (II) is more puckered than in (I). In (II), morpholin ring adopts a chair conformation. Although the oxime moiety in (I) has an E configuration, the oxime moiety in (II) has a Z configuration The molecules in (I) are linked by O–H...O and C–H...π(benzene) interactions, forming a two-dimensional network, while the molecules in (II) are connected by O–H...N interaction.

Pyrimidine cyclobutane dimers are hazardous DNA lesions formed upon exposure of DNA to UV light, which can be repaired through oxidative electron transfer (ET). Laser flash photolysis and computational studies were performed to explore the role of configuration and constitution at the cyclobutane ring on the oxidative repair process, using the nitrate radical (NO3•) as oxidant. The rate coefficients of 8–280 × 107 M−1 s−1 in acetonitrile revealed a very high reactivity of the cyclobutane dimers of N,N’-dimethylated uracil (DMU), thymine (DMT), and 6-methyluracil (DMU6-Me) towards NO3•, which likely proceeds via ET at N(1) as a major pathway. The overall rate of NO3• consumption was determined by (i) the redox potential, which was lower for the syn- than for the anti-configured dimers, and (ii) the accessibility of the reaction site for NO3•. In the trans dimers, both N(1) atoms could be approached from above and below the molecular plane, whereas in the cis dimers, only the convex side was readily accessible for NO3•. The higher reactivity of the DMT dimers compared with isomeric DMU dimers was due to the electron-donating methyl groups on the cyclobutane ring, which increased their susceptibility to oxidation. On the other hand, the approach of NO3• to the dimers of DMU6-Me was hindered by the methyl substituents adjacent to N(1), making these dimers the least reactive in this series.

Eremophilane-type sesquiterpene lactones from Ligularia hodgsonii Hook

The discovery and large-scale synthesis of fullerenes have aroused interdisciplinary interest in these closed-cage molecules1,2,3,4,5,6. C60 can be photopolymerized into a form in which the cages are thought to be linked by cyclic C4 units in a [2 + 2] cycloaddition7, provoking theoretical studies of the C60 dimer8,9,10,11,12,13,14,15, the smallest subunit of such a polymer. The C60 dimers C120O (refs 16, 17), C121H2( ref. 17) and C120O2(ref. 18) have been reported, in which the two C60molecules are linked by, respectively, a furan group, a cyclopentane ring and a cyclobutane ring plus two oxygen bridges; but the simplest dimer, C120linked by a cyclobutane ring alone, has not so far been observed. We now report that this dumb-bell-shaped molecule can be synthesized by a solid-state mechanochemical reaction of C60 with potassium cyanide. Our X-ray structural analysis shows that the C4 ring connecting the cages is square rather than rectangular—the latter is predicted theoretically8,9,13,14,15. The dimer dissociates cleanly into two C60 molecules on heating or one-electron reduction, but in the gas phase during mass-spectrometric measurements it undergoes successive loss of C2 units, shrinking to even-numbered fullerenes such as C118 and C116 in a sequence similar to that seen for other large fullerenes19,20.

The photochemical behaviour of fifteen derivatives of head-to-head coumarin dimers has been investigated. The photocleavage of the cyclobutane rings in these compounds in solution occurs on irradiation with light of wavelength 277 ± 10 nm to give two molecules of coumarin derivatives via symmetric fission and/or 2,2′-dihydroxystilbene and fumaric (and maleic) acid derivatives via asymmetric fission. The direction of these photofissions is primarily affected by the basic structure of the coumarin dimer derivative, the photocleavage proceeding exclusively with retention of the ring structure when the derivative has a stable five- or six-membered ring fused to its cyclobutane ring. A secondary influence is the steric repulsion between the substituents attached to the cyclobutane ring.

The aromatic herb Plectranthus neochilus with a cannabis smell, widely used in folk medicine, has become the subject of a study of its essential oils of flowers and leaves. GC-MS analysis revealed a unique composition, the oils of flowers, the main component of which is 2-methyl-1-butene, its concentration exceeds 87 percent. On the one hand, this is very unusual data, although, on the other hand, it is known that 2-methyl-1-butene can be a product of thermal decomposition of 1,1-dimethyl-cyclopropane. However from a microbiological point of view, 2-methyl-1-butene can be a product of bacterial reduction of isoprene by a mixture of Comamonas sp. and Acetobacterium wieringae bacteria. This issue is extremely interesting and requires further careful study, although a preliminary discussion is given in the discussion of this phenomenon. Analysis of the oil from the leaves showed that the main products are α-thujene and α-pinene, the content of which exceeds 75 percent. According to a detailed analysis of the species Plectranthus, it was found that this species is a producer of volatile metabolites containing cyclopropane and cyclobutane rings. It is assumed that the compounds of essential oils containing cyclopropane and cyclobutane rings may be the main biologically active substances in this species or genus of plants. Data on the biological activity of the main identified compounds of this aromatic plant are presented..

In the title compound, C(21)H(15)NO(3), which is one of the photoreaction products of N-methyl-1,8-naphthalenedicarboximide with phenylacetylene, the cyclobutene and epoxy rings are trans to each other across the cyclohexene ring of the tetralin moiety. The dihedral angle between the mean planes of the cyclobutene and cyclohexene rings is 112.80 (2) degrees, while the latter makes a dihedral angle of 103.70 (9) degrees with the epoxy ring. The crystal structure is stabilized by C-H...O intermolecular interactions.

Crystal structure, DNA-binding ability and cytotoxic activity of platinum(II) 2,2 ′-dipyridylamine complexes

The photodimerization reaction inp-bromocinnamic acid (p-BCA) in the crystalline state has been probed by Raman phonon spectroscopy. Monotonic redshift of the phonon bands and nonappearance of any new phonon bands on reaction progress suggest that the reaction is homogeneous and the reactant and the product form a solid solution. It is further observed that a low frequency phonon at 18·6 cm−1 softens on photoexcitation and progress of reaction. The photoreaction inp-BCA crystal therefore seems to be mediated by the lattice phonon. In the IR spectrum disappearance of the aliphatic > C=C < stretching frequency and appearance of cyclobutane ring deformation and ring stretching modes on reaction confirm photodimerization by cyclobutane ring formation. Considerable overlap between the absorption and emission bands shows that the exciton-phonon coupling is not very strong in the monomer crystal.

Ring cleavage rearrangement of cyclobutylmethylboranes

Carboplatin derivatives with superior antitumor activity compared to the parent compound

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