Metallic chalcogenolates mediated modular Michael-aldol cascade reaction: an easy route to multi-functionalized chalcogenides and Morita-Baylis-Hillman adducts

Chalcogenolate mediated Michael-aldol cascade reactions consists of a very efficient route to multi-functionalized gamma-hydroxichalcogenides. Although, when selenolates are employed, these gamma-hydroxichalcogenides can be readily converted into the corresponding Morita-Baylis-Hillman adducts by oxidative elimination of the selenium moiety. In this context, herein we present a complete study on the scope and limitations of this reaction. (C) 2012 Elsevier Ltd. All rights reserved.

On the formation of carbonate adducts of fatty alcohols, sterols, and sugars in biological conditions

The formation and properties of carbonate adducts of some organic hydroxy compounds in aqueous medium were investigated. Fatty alcohols and sugars were chosen as representative classes of biological interest, and the medium was carbonated aqueous solution with pH ranging from 3.0 to 8.3. Capillary electrophoresis with two capacitively coupled contactless conductivity detectors (C4Ds) was used for quantitation and to obtain the mobility of the monoalkyl carbonates (MACs), which were used to determine the equilibrium and kinetic constants of the reaction as well as the diffusion coefficients. For increasing chain length of the alcohols, the equilibrium constant tends to the unit, which suggests that fatty alcohols can form the corresponding MACs. The formation of MACs for cyclohexanol and cyclopentanol also suggest the existence of similar species for sterols. Carbonate adducts of fructose, glucose, and sucrose were also detected, which suggests that these counterparts of the well-known phosphates can also occur in the cytosol. Our calculations suggest that one in 1000 to one in 10 000 molecules of these hydroxy compounds would be available as the corresponding MAC in such a medium. Experiments carried out at pH values less than 3.0 showed that there is a catalytic effect of hydronium on the interconversion of bicarbonate and a MAC. Taking into account the great number of hydroxy compounds similar to the ones investigated and that bicarbonate is ubiquitous in living cells, one can anticipate the existence of a whole new class of carbonate adducts of these metabolites.

Stereoselective synthesis of novel diels-alder adducts of p-substituted Methyl Thiocinnamates and Cyclopentadiene

This article describes the Diels-Alder reaction between methyl thiocinnamates, substituted at the para position by electron-donating and electron-withdrawing groups, with cyclopentadiene in the presence of catechol boron bromide (CBB) as a Lewis acid catalyst. The adduct configuration was confirmed by H-1 NMR coupling constants and single-crystal x-ray diffraction. Total endo stereoselectivity was observed in all reactions and was attributed to the effective secondary interaction between the boron atom and the incipient double bond in the norbonene resulting from the planar geometry of the catalyst. C-13 NMR chemical shifts of the coordinated dienophile carbonyl carbons with CBB compared to those of the non coordinated thiocinammates suggest a strong complexation with the catalyst.

Crystal structure and spectroscopic properties of polymeric adducts of the tetra-mu-haloaspirinate-dicopper(II)

Eight new copper(II) complexes with halo-aspirinate anions have been synthesized: [Cu-2(Fasp)(4)(MeCN)(2)] center dot 2MeCN (1), [Cu-2(Clasp)(4)(MeCN)(2)]center dot 2MeCN (2), [Cu-2(Brasp)(4) (MeCn)(2)] center dot 2MeCn (3), {[Cu-2(Fasp)(4)(Pyrz)] center dot 2MeCN}(n) (4) {[Cu-2(Clasp)(4)(Pyrz)] center dot 2MeCN}(n) (5), [Cu-2(Brasp)(4)(Pyrz)](n) (6), [Cu-2(Clasp)(4)(4,4'-Bipy)](n) (7), and [Cu-2(Brasp)(4)(4,4'-Bipy)](n) (8) (Fasp: fluor-aspirinate; Clasp: chloro-aspirinate; Brasp: bromo-aspirinate; MeCN: acetonitrile; Pyrz: pyrazine; 4,4'-Bipy: 4,4'-bipyridine). The crystal structure of two 2 and 4 have been determined by X-ray diffraction methods. All compounds have been studied employing elemental analysis, IR, and UV-Visible spectroscopic techniques. The results have been compared with previous data reported for complexes with similar structures.

A Facile, Versatile, and Mild Morita-Baylis-Hillman-Type Reaction for the Modular One-Pot Synthesis of Highly Functionalized MBH Adducts

MoritaBaylisHillman derivatives have been extensively investigated as intermediates in the preparation of important classes of compounds. However, there are intrinsic limitations regarding the structure of the Michael electrophile acceptors, the aldehydes, and the catalysts. Therefore, this transformation has several drawbacks, including, for example, its long reaction times. Herein we present a simple, general, fast, and high-yielding protocol for the one-pot synthesis of MoritaBaylisHillman derivatives. Our approach is driven by a lithium selenolate Michael/aldol operation with concomitant O-functionalization/selenoxide elimination cascade sequences.

Studies of pure rotational spectra of isolated molecules and molecular adducts using pulsed jet Fourier transform microwave (PJ-FTM) spectroscopy

This thesis focuses on studying molecular structure and internal dynamics by using pulsed jet Fourier transform microwave (PJ-FTMW) spectroscopy combined with theoretical calculations. Several kinds of interesting chemical problems are investigated by analyzing the MW spectra of the corresponding molecular systems. First, the general aspects of rotational spectroscopy are summarized, and then the basic theory on molecular rotation and experimental method are described briefly. ab initio and density function theory (DFT) calculations that used in this thesis to assist the assignment of rotational spectrum are also included. From chapter 3 to chapter 8, several molecular systems concerning different kind of general chemical problems are presented. In chapter 3, the conformation and internal motions of dimethyl sulfate are reported. The internal rotations of the two methyl groups split each rotational transition into several components line, allowing for the determination of accurate values of the V3 barrier height to internal rotation and of the orientation of the methyl groups with respect to the principal axis system. In chapter 4 and 5, the results concerning two kinds of carboxylic acid bi-molecules, formed via two strong hydrogen bonds, are presented. This kind of adduct is interesting also because a double proton transfer can easily take place, connecting either two equivalent or two non-equivalent molecular conformations. Chapter 6 concerns a medium strong hydrogen bonded molecular complex of alcohol with ether. The dimer of ethanol-dimethylether was chosen as the model system for this purpose. Chapter 7 focuses on weak halogen…H hydrogen bond interaction. The nature of O-H…F and C-H…Cl interaction has been discussed through analyzing the rotational spectra of CH3CHClF/H2O. In chapter 8, two molecular complexes concerning the halogen bond interaction are presented.

From Structure to Function: Characterization of Cu(I) Adducts in Leveler Additives by DFT Calculations

We present the first molecular model of the coordination complex formed by Cu(I) and imidazole-epichlorohydrin polymers. Our calculations show that the Cu(I) ion has linear coordination and the whole complex has neutral charge. Our model suggests salt couple pairing as the driving force for the formation of the surface-confined precipitation, which is crucial to obtain flat surfaces in industrial copper deposition processes, required for mass fabrication of state-of-the-art electronic and memory devices.

Alternate, Easy and practical synthesis of allyl amines from acetyl derivatives of Baylis-Hillman adducts using Methanolic Ammonia

A methanolic ammonia-mediated alternate, easy and practical stereoselective synthesis of allyl amines from the acetyl derivatives of Baylis-Hillman adducts is described.

A reinvestigation into the reaction of NH4OAc with acetyl derivatives of Bay-lis-Hillman adducts: Formation of tertiary and secondary allyl amines in-stead of primary allyl amines

A reinvestigation into the reaction between ammonium acetate and the acetyl derivatives of Baylis-Hillman adducts has led us to conclude that the products obtained are tertiary and secondary allyl amines and not the primary allyl amines. The unambiguous assignment of the structure of products using chemical and spectroscopic methods is described

Studies on the reduction of the nitro group in 3-aryl-2-methylene-4-nitro-alkanoates afforded by the Baylis-Hillman adducts: Synthesis of 4-aryl-3-methylene-2-pyrrolidinones and 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylates

The formation of substituted 2-pyrrolidinones and indoles by the reduction of the secondary nitro group in appropriate 3-aryl-2-methylene-4-nitroalkanoates afforded by Baylis-Hillman chemistry via different reducing agents is described. The 3-aryl-2-methylene-4-nitroalkanoate obtained from SN2 nucleophilic reaction between the acetate of Baylis-Hillman adducts and ethyl nitroacetate upon reduction with indium-HCl furnishes a mixture of cis and trans substituted phenyl-3-methylene-2-pyrrolidinones. In contrast, similar reductions of analogous substrates derived from nitroethane stereoselectively furnished only the trans substituted phenyl-3-methylene-2-pyrrolidinones. On the other hand the SnCl2.2H2O-promoted reductions of substrates derived from nitro ethylacetate give oxime derivatives while the ones obtained from nitroethane yield a mixture of cis and trans 4-aryl-3-methylene-2-pyrrolidinones. Alternatively, the SnCl2.2H2O-promoted reduction of substituted 2-nitrophenyl-2-methylene-alkanoate furnished from ethyl nitroacetate yields 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylate while indium-promoted reaction of this substrate leads to a complex mixture. Analogous reactions with SnCl2.2H2O of substituted 2-nitrophenyl-2-methylene-alkanoate obtained from nitroethane yield 4-alkyl-3-methylene-2-quinolones in moderate yields

Studies toward the construction of substituted piperidine-2-ones and pyridine-2-ones from Baylis-Hillman adducts: Discovery of a facile synthesis of 5-methyl-4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates

Studies toward the construction of functionalised piperidone derivatives from derivatives of Baylis-Hillman adducts are described. Interestingly the 6-oxo-4-aryl-piperidine-3-carboxylates generated during the study serve as precursor for the facile synthesis of 4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates

Odorless Preparation Of Thioglycosides And Thio Michael Adducts Of Carbohydrate Derivatives

A generalized, odorless, one-pot methodology has been developed for the preparation of 1,2-trans-thioglycosides and thio-Michael addition products of carbohydrate derivatives through triphenyl phosphine mediated cleavage of disulfides and reaction of the thiolate formed in situ with glycosyl bromides and glycosyl conjugated alkenes.

Application of primary allyl amines afforded by the Baylis-Hillman adducts for heterocyclic synthesis: Generation of 5-benzyl-4(3H)-pyrimidinones and 2-benzylidene-2,3-dihydro-pyrrolizin-1-ones

The applications of the primary allyl amines afforded by the acetyl derivative of Baylis-Hillman adducts of acrylate for the synthesis of heterocycles using robust reactions are described. In the first strategy a one-pot synthesis of 5-benzyl-4(3H)-pyrimidinones have been achieved via N-formylation of the amines in the presence of neat formamide followed by ammonium formate-mediated cyclization. These pyrimidinones have been demonstrated to be excellent precursor to the 4-pyridinamine derivatives. In the second strategy the synthesis of 2-benzylidene-2,3-dihydro-pyrrolizin-1-ones have been accomplished via treatment of allyl amine with dimethoxyfuran followed by saponification and PPA-mediated intramolecular cyclization.

Tandem Mass Spectrometric Analysis of Metallocene Adducts with Short Oligonucleotides

Metallocene dichlorides constitute a remarkable class of antineoplastic agents that are highly effective against several cancer cell lines. They were shown to accumulate in the DNA-rich region, which suggests DNA as the primary target. These compounds exhibit two cyclopentadienyl ligands and two labile halide ligands, resulting in a bent sandwich structure. The cis-dihalide motif is structurally related to the cis-chloro configuration of cisplatin and similar modes of action can thus be assumed. Cisplatin binds to two neighboring guanine nucleobases in DNA and consequently, distorts the double-helix, thereby inhibiting DNA replication and transcription. Platinum is classified as a soft Lewis acid and binds preferentially to the nitrogen atoms within the nucleobases. The metallocene dichlorides investigated in this study comprise the metal centers Ti, V, Nb, Mo, Hf, and W, which are classified as hard or intermediate Lewis acids, and thus, favor binding to the phosphate oxygen. Although several studies reported adduct formation of metallocene dichlorides with nucleic acids, substantial information about the adduct composition, the binding pattern, and the nucleobase selectivity has not been provided yet. ESI-MS analyses gave evidence for the formation of metallocene adducts (M = Ti, V, Mo, and W) with single-stranded DNA homologues at pH 7. No adducts were formed with Nb and Hf at neutral pH, albeit adducts with Nb were observed at a low pH. MS2 data revealed considerable differences of the adduct compositions. The product ion spectra of DNA adducts with hard Lewis acids (Ti, V) gave evidence for the loss of metallocene ligands and only moderate backbone fragmentation was observed. By contrast, adducts with intermediate Lewis acids (Mo, W) retained the hydroxy ligands. Preliminary results are in good agreement with the Pearson concept and DFT calculations. Since the metallodrugs were not lost upon CID, the nucleobase selectivity, stoichiometry, and binding patterns can be elucidated by means of tandem mass spectrometry.

Involvement of HMGB1 in the repair of DNA adducts and the responses to DNA damage in mammalian cells

High mobility group protein B1 (HMGB1) is a multifunctional protein with roles in chromatin structure, transcription, V(D)J recombination, and inflammation. HMGB1 also binds to and bends damaged DNA, but the biological consequence of this interaction is not clearly understood. We have shown previously that HMGB1 binds cooperatively with nucleotide excision repair (NER) damage recognition proteins XPA and RPA to triplex-directed psoralen DNA interstrand crosslinks (ICLs). Based on this we hypothesized that HMGB1 is enhancing the repair of DNA lesions, and through this role, is affecting DNA damage-induced mutagenesis and cell survival. Because HMGB1 is also a chromatin protein, we further hypothesized that it is acting to facilitate chromatin remodeling at the site of the DNA damage, to allow access of the repair machinery to the DNA lesion. We demonstrated here that HMGB1 could bind to triplex-directed psoralen ICLs in a complex with NER proteins XPC-RAD23B, XPA and RPA, which occurred in the presence or absence of DNA. Supporting these findings, we demonstrated that HMGB1 enhanced repair of triplex-directed psoralen ICLs (by nucleotide incorporation), as well as removal of UVC irradiation-induced DNA lesions from the genome (by radioimmunoassay). We also explored HMGB1's role in chromatin remodeling upon DNA damage. Immunoblotting demonstrated that, in contrast to HMGB1 proficient cells, cells lacking HMGB1 showed no increase in histone acetylation after UVC irradiation. Additionally, purified HMGB1 protein enhanced chromatin formation in an in vitro chromatin assembly system. However, HMGB1 also has a role in DNA repair in the absence of chromatin, as shown by measuring UVC-induced nucleotide incorporation on a naked substrate. Upon exploration of HMGB1's effect on several cellular outcomes of DNA damage, we found that mammalian cells lacking HMGB1 were hypersensitive to DNA damage induced by psoralen plus UVA irradiation or UVC radiation, showing less survival and increased mutagenesis. These results reveal a new role for HMGB1 in the error-free repair of DNA lesions in a chromosomal context. As strategies targeting HMGB1 are currently in development for treatment of sepsis and rheumatoid arthritis, our findings draw attention to potential adverse side effects of anti-HMGB1 therapy in patients with inflammatory diseases. ^