Copper Catalyzed Asymmetric [4＋2] Annulations of D-A Cyclobutanes with Aldehydes

Copper catalyzed enantioselective [4＋2] annulations of D-A cyclobutanes and aldehydes have been developed. In the presence of a side arm modified chiral bisoxazoline （SaBOX） ligand, the [4＋2] annulations proceeded smoothly with a broad substrate scope. 22 examples were studied, leading to the corresponding products with various functional groups in 41%-99% yields with 〉99/1 dr and 90%-96% ee. The resulting product with two ester groups was mono-reduced, giving the corresponding product in excellent diastereoselectivity without loss of the enantiopurity.

Synthesis of carborane-fused cyclobutenes and cyclobutanes

Transmetalation of carborane-fused zirconacycles to Cu（II） induces the C-C coupling reaction to form four-membered rings. This serves as a new efficient and general methodology for the generation of a series of carborane-fused cyclobutenes and cyclobutanes. A reaction mechanism involving transmetalation to Cu（II） and reductive elimination is proposed.

Cyclobutane Pyrimidine Dimer Accumulation in Relation to UV-B Sensitivity in Rice Cultivars

Five rice ( Oryza sativa L.) cultivars, widely planted in South China, were grown in greenhouse with or without supplemental UV_B radiation at level of 13.6 kJ·m -2 ·d -1 . After 15 day_UV_B treatment, significant intraspecific differences were observed in plant height, photosynthetic rate and total biomass. Based on the total biomass accumulation, cultivar “Tesanai” was found to be the most sensitive, and cultivar “Luhuangzhan” was the most tolerant species to UV_B radiation. UV_B induced cyclobutane pyrimidine dimer (CPD) in rice DNA were quantified by ELISA with specific monoclonal antibody. CPD accumulations in DNA extracted from 5 rice cultivars were remarkably increased by UV_B radiation, and it was confirmed that there was a strong positive correlation between CPD accumulation and the inhibition of total biomass. Photorepair was proved to be the predominant mode of CPD repair in UV_B irradiated rice. Light_dependent removal of CPD was very fast as compared with dark repair. Different levels of CPD accumulation among rice cultivars were related with different capacity of CPD photorepair. Capacity of light_dependent CPD removal may play an important role in UV_B resistance of rice.

Mechanochemistry of cyclobutanes

The field of polymer mechanochemistry has been revolutionized by implementing force-responsive functional groups—mechanophores.The rational design of mechanophores enables the controlled use of force to achieve constructive molecular reactivity and material responses.While a variety of mechanophores have been developed,this Mini Review focuses on cyclobutane,which has brought valuable insights into molecular reactivity and dynamics as well as innovations in materials.We discuss its reactivity and mechanism,dynamics and stereoselectivity,as well as impacts on material properties.

Exploratory Study of Laser-induced Thymine-thymine Dimer in DNA by RP-HPLC

The relationship between the yield of thymime-thymine dimer after laser irradiation and physical parameters, such as intensity and pulse number was studied to explore the function of laser irradiation to induce thymine-thymine dimer. A modified high-performance liquid chromatography (HPLC) method has been developed for the determination of thymine-thymine dimer in DNA for. The thymine-thymine dimer was prepared by a photochemical reaction to be used as the standard substance. The HPLC method we proposed is not interfered by other hydrolysate from DNA. The stability and reproducibility are good, and it can determine as little as 4.42×10 -5 μg·mL -1 thymime-thymine dimer. Three levels of laser intensity to irradiate DNA were selected from calf thymine to test the influence of the pulse number. The mechanism of DNA lesion and repair caused by laser irradiation was studied preliminarily.

Effects of temperature on UV-B-induced DNA damage and photorepair in Arabidopsis thaliana

DNA damage in the form of cyclobutane pyrimidine dimers(CPDs) and (6-4) photoproducts(6-4PPs) induced by UV-B radiation in Arabidopsis thaliana at different temperatures was investigated using ELISA with specific monoclonal antibodies. CPDs and 6-4PPs increased during 3 h UV-B exposure, but further exposure led to decreases. Contrary to the commonly accepted view that DNA damage induced by UV-B radiation is temperature-independent because of its photochemical nature, we found UV-B-induction of CPDs and 6-4PPs in Arabidopsis to be slower at a low than at a high temperature. Photorepair of CPDs at 24℃ was much faster than that at 0℃ and 12℃, with 50% CPDs removal during 1 h exposure to white light. Photorepair of 6-4PPs at 12℃ was very slow as compared with that at 24℃, and almost no removal of 6-4PPs was detected after 4 h exposure to white light at 0℃. There was evidence to suggest that temperature-dependent DNA damage and photorepair could have important ecological implications.

Synthesis and Crystal Structure of Rctt-1-(2-benzoxazolyl)-2-(4-chlorophenyl)-4-phenyl-3-(4-pyridinyl)cyclobutane

The title compound (C28H21ClN2O, Mr = 436.92) was synthesized by the cross- photodimerization of (E)-2-(2-phenylethenyl)benzoxazole and (E)-4-[2-(4-chlorophenyl)ethenyl]- pyridine in sulfuric acid solution. Its molecular structure has been unequivocally determined by X-ray crystallography. The title compound belongs to triclinic system, space group P?with cell parameters: a = 9.648(3), b = 10.458(4), c = 12.106(4) , a = 89.089(7), b = 75.644(6), g = 68.441(7)? V = 1096.7(7) 3, Z = 2, Dc = 1.323 g/cm3, F(000) = 456 and m(MoKa) = 0.198 mm-1. The final R and wR are 0.0627 and 0.1285, respectively for 1737 observed reflections with I > 2s(I). S = 0.921 and (/s)max = 0.001. The cyclobutane ring has a puckered conformation with four different aryl groups substituted on each carbon atom. The dihedral angles of the cyclobutane ring are 20.2 and 20.6? The bond distances of the cyclobutane ring are 1.541, 1.555, 1.560 and 1.563 ? respectively, which are slightly longer than that of the normal CC single bond. The title compound is the only cross-dimer and its two heteroaryl groups are situated at the trans-1,3 position of the cyclobutane ring, revealing that the cross-photodimerization proceeds in a head-to-tail pattern with high stereo-selectivity.

Molecular Dynamics Insights into Electron-Catalyzed Dissociation Repair of Cyclobutane Pyrimidine Dimer

Excess electrons are not only an important source of radiation damage,but also participate in the repair process of radiation damage such as cyclobutane pyrimidine dimer(CPD).Using ab initio molecular dynamics(AIMD)simulations,we reproduce the single excess electron stepwise catalytic CPD dissociation process in detail with an emphasis on the energy levels and molecular structure details associated with excess electrons.On the basis of the AIMD simulations on the CPD aqueous solution with two vertically added excess electrons,we exclude the early-proposed[2+2]-like concerted synchronous dissociation mechanism,and analyze the difference between the symmetry of the actual reaction and the symmetry of the frontier molecular orbitals which deeply impact the mechanism.Importantly,we propose a new model of the stepwise electron-catalyzed dissociation mechanism that conforms to the reality.This work not only provides dynamics insights into the excess electron catalyzed dissociation mechanism,but also reveals different roles of two excess electrons in two bond-cleavage steps(promoting versus inhibiting).

One-dimensional Coordination Polymers of rctt-1,3-Diphenyl-2,4-bis[2-(5-phenyl)-oxazolyl]cyclobutane with CuCl_2 and CoCl_2

The Cu（Ⅱ） and Co（Ⅱ） supramolecular coordination polymers, [CuCl2（DPO）- （CH3CN）0.5（CH2Cl2）0.5]n （CuDPO, DPO = rctt-1,3-diphenyl-2,4-bis[2-（5-phenyl）oxazolyl]cyclo- butane） and [CoCl2（DPO）]n （CoDPO）, were synthesized and characterized by single-crystal X-ray diffraction method. CuDPO crystallizes in monoclinic, space group P21/n, with a = 11.243（5）, b = 16.070（8）, c = 19.872（9） A, β = 95.678（10）°, Z = 4, V= 3573（3） A3, C35.50H28.50Cl3CuN2.50O2, Mr = 692.00, Dc = 1.287 g/cm3, p = 0.868 mm^-1, F（000） = 1420, S = 1.089, （△/σ）max = 0.069, the final R = 0.0682 and wR = 0.1749. CoDPO is of monoclinie, space group P21/n, with a = 11.396（4）, b = 15.151（5）, c = 17.673（6） A, β = 90.528（6）°, Z = 4, V = 3051.4（17） A3, C34H26Cl2CoN2O2, Mr = 624.40, Dc = 1.359 g/cm3, μ = 0.770 mm^-1, F（000） = 1284, S = 0.981, （△/σ）max = 0.001, the final R = 0.0471 and wR = 0.0961. In each case, the metal cation is coordinated by two C1 anions and two N atoms from oxazole ring of the ligands, which leads to the formation of a one-dimensional polymeric structure. It is found that the cyclobutane ring of coordinated DPO adopts a distorted conformation in the crystal, which is attributed to the increased steric effect between adjacent aryl substituents for the coordination of oxazole ring to metal cation. Thermal gravimetric analysis of the two complexes was also observed.

d-limonene prevents ultraviolet irradiation:Induced cyclobutane pyrimidine dimers in Skh1 mouse skin

AIM: To establish whether d-limonene can protect against induction of cyclobutane pyrimidine dimers(CPDs) and sunburn in ultraviolet irradiation(UVR) irradiated mouse skin. METHODS: The d-limonene was given in 4 daily oral 20 μL aliquots at different concentrations as follows: 100%, 10% or 1% in liponate and 100% liponate as control. One day after the final d-limonene treatment, the mice were anesthetized with i.p. sodium pentobarbital and placed in boxes to allow a rectangular(2 cm × 4 cm) region of dorsal skin to be irradiated with a single, ultraviolet radiation dose of 1.5 kJ /m2. Skin samples from UVR irradiated area were obtained at 5 min after UVR exposure for CPD detection, at 6 d after UVR exposure, skin samples were obtained for in situ analysis for N-myc downstream regulating gene 1(NDRG1)(a stress response gene), proliferating cell nuclear antigen(PCNA)(an S-phase marker) and filaggrin(a barrier integrity gene). Based on immunohistochemistry staining, the number of CPD, NDRG1 and PCNA positive cells, as well as unstained cells was counted in 3 different individually selected areas and percentage of positive cells was established. RESULTS: CPD reduction occurred as follows: liponate only-none; 1% d-limonene-54.3% reduction of CPDs; 10% d-limonene-73.4% reduction of CPDs; 100% d-limonene-86.1% reduction of CPDs, the latter equivalent to a UV dose of only 0.21 k J/m2. Sunburn was also dose-dependently reduced by d-limonene. The NDRG1 protein was strongly induced by UVR(70.0% ± 10.4% positive cells), but 1% d-limonene reduced the response to 64.6% ± 9.2%, 10% d-limonene reduced the response to 16.2% ± 3.4% and 100% d-limonene reduced the response to 6.3% ± 1.7%. Similarly, PCNA was 52.4% ± 9.9% positive in UVR exposed skin, and 1% d-limonene reduced it to 42.9% ± 8.1%, 10% d-limonene reduced it to 36.2% ± 6.7% and 100% d-limonene reduce it to 13.8% ± 3.4%. NDRG1 and PCNA were increased by d-limonene or UVR separately, but combined they produced less than either agent separately owing to the protective effect of pre-exposure to d-limonene. CONCLUSION: Overall d-limonene acted to protect against ultraviolet B-induced DNA photodamage and sunburn in UVR exposed skin.

Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic synthesis.We report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available dichlorocyclobutanones.The substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic conditions.Further transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

Contemporary synthesis of bioactive cyclobutane natural products

Many cyclobutane natural products have intriguing biological properties that arise from their fascinating chemical structures.Cyclobutane natural products feature a cyclobutane scaffold as the core or as a part of the spirocyclic or fused cyclic core.However,the highly functionalized nature and the inherent stereochemistry of these cyclobutane natural products,which are associated with their biological activities,pose tremendous challenges to their preparation.In this perspective,we present contemporary advancements in synthetic methods and/or strategies en route to the bioactive cyclobutane natural products.We begin by describing the representative bioactive cyclobutane natural products and then focus on illustrative examples of their syntheses reported from 2018 to 2021.These advances will enable efficient syntheses of cyclobutanes of structural and biological importance.

Aggregation-Enabled Intermolecular Photo[2+2]cycloaddition of Aryl Terminal Olefins by Visible-Light Catalysis

Photo[2+2]cycloaddition of olefins is a sought-after tool for making cyclobutanes,which are the building blocks for a wide range of biologically active molecules and natural products.However,the formation of cyclobutane derivatives from aryl terminal olefins is problematic due to their high redox potential,and high energy in the excited state,making visible-light-absorbing photocatalyst difficult to realize either electron or energy transfer to olefins during the photocyclic addition process.Herein,we report,for the first time,the aggregationinduced photo[2+2]cycloaddition of two olefins by visible-light catalysis in homogeneous solution.An array of control experiments and spectroscopic analyses reveal that the terminal olefins tend to aggregate to form excimers/exciplexes,which possess much lower energy than their monomeric forms,and enables triplet energy transfer from excited Ir(ppy)3*to supramolecular self-assembly feasible,leading to homo and cross[2+2]photodimerization of the olefins to fabricate cyclobutanes at ambient conditions in good to excellent yields.

Methodology-driven efficient synthesis of cytotoxic(±)-piperarborenine B

The evolution of synthetic design toward the efficient synthesis of cyclobutane natural product(±)-piperarborenine B is demonstrated.Taking the advantages of good functional group compatibility of contractive synthesis of cyclobutanes from pyrrolidines,stereoselective synthesis of unsymmetric highly functionalized cyclobutanes core of(±)-piperarborenine B was realized in one step.Also,an unprecedented carboxylic acid assisted-diastereoselective Kracho decarboxylation/transmethylation features a new strategy for a non-symmetrical cyclobutane core.The synthesis of(±)-piperarborenine B illustrates the advancement of methodology resulting in the improvement in synthetic efficiency.

Kinetics and mechanism of electron-induced splitting of a cyclobutane pyrimidine dimer with or without an electron acceptor

Utilizing a pulse radiolysis equipment with time-resolved optical detector, kinetic processes of electron-induced splitting of cis-syn 1,3-dimethyluracil cyclobutane dimer (DMUD) in aqueous solution were investigated in the presence or absence of riboflavin (RF) or flavin adenine dinucleotide (FAD). It has been observed that the cyclobutane pyrimidine dimer reacting with hydrated electron splits spontaneously to give a monomer and a monomer radical anion, and the anion transfers one electron to RF or FAD. From the buildup kinetics of radical species, the rate constants of electron transfer from the monomer radical anion to RF and FAD have been determined. On the basis of comparison of the interactions between DMUD and hydrated electron in the presence and absence of RF or FAD, a chain reaction process in the absence of RF or FAD has been demonstrated.

Recent advances in the applications of[1.1.1]propellane in organic synthesis

As a highly strained small molecule,[1.1.1]propellane has been widely used in various synthetic transformations owing to the exceptional reactivity of the central bond between the two bridgehead carbons.Utilizing strain-release approaches,the rapid development of strategies for the construction of bicyclo[1.1.1]pentane(BCP)and cyclobutane derivatives using[1.1.1]propellane as the starting material has been witnessed in the past few years.In this review,we highlight the most recent advances in this field.Accordingly,the reactivity of[1.1.1]p ropellane can be divided into three pathways,including radical,anionic and transition metal-catalyzed pathways under appropriate conditions.

Oxidative Splitting of a Pyrimidine Cyclobutane Dimer: A Pulse Radiolysis Study

The oxidative splitting process of cis-syn 1,3-dimethyluracil cyclobutane dimer (DMUD) in aqueous solution was investigated using pulse radiolysis technique. The results indicated that DMUD can be splitted into 1,3-dimethyluracil (DMU) by OH radicals (OH ·) and Br_2 radical anions (Br ·-_2), but not by azide radicals (N ·_3). The oxidative mechanisms that an H-abstracted from DMUD for OH · oxidative splitting and an electron transfer from DMUD to Br ·-_2, were suggested. Related kinetic parameters were determined.

Skeletal contraction:A novel strategy to access multisubstituted cyclobutane

The polysubstituted and spirocyclic cyclobutanes were efficiently constructed by the utilization of a novel skeletal contraction strategy which only took one-step synthesis from the readily accessible pyrrolidines.The mechanistic studies indicated that a key intermediate N-aminated pyrrolidine was formed initially and subsequent extrusion of a nitrogen via a radical pathway completed the transformation.This practical methodology was further highlighted by the concise,formal synthesis of the cytotoxic natural product piperarborenine B.