A New Tetrahydrofurannulation Via Tandem Radical Cyclization Reaction-Reductive Deoxygenation Sequence

Treatment of bromoketals 2, derived from allyl alcohols 1, with tributyltin chloride, sodium cyanoborohydride and AIBN furnishes the tetrahydrofurannulated products 3 via a 5-exo-trig radical cyclisation reaction followed by reductive cleavage of ketal 4.

Crystal and molecular structure of the quinoxaline antibiotic analog TANDEM (des-N-tetramethyltriostin A)

The crystal structure of TANDEM (des-N-tetramethyltriostin A), a synthetic analogue of the quinoxaline antibiotic triostin A, has been determined independently at -135 and 7 'C and refined to R values of 0.088 and 0.147, respectively. The molecule has approximate 2-fold symmetry, with the quinoxaline chromophores and the disulfide cross-bridge projecting from opposite sides of the peptide ring. The quinoxaline groups are nearly parallel to each other and separated by about 6.5 A. The peptide backbone resembles a distorted antiparallel 13 ribbon joined by intramolecular hydrogen bonds N-H(LVal)--O(L-Ala). At low temperatures, the TANDEM molecule is surrounded by a regular first- and second-order hydration sphere containing 14 independent water molecules. At room temperature, only the first-order hydration shell is maintained. Calculations of the interplanar separation of the quinoxaline groups as a function of their orientation with respect to the peptide ring support the viability of TANDEM to intercalate bifunctionally into DNA.

Tributyltin chloride-sodium cyanoborohydride mediated tandem radical cyclisation-reductive demethoxylation sequence

Reaction of the bromoketals 3, 7a-g and 11 with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of AIBN furnished the ethers 5, 8a-g and 13 via a tandem sequence comprising of a radical cyclisation reaction and tri-n-butylhalostannane and sodium cyanoborohydride mediated reductive demethoxylation of the resulting cyclic ketals.

Convenient Synthesis of Ferrocene Conjugates Mediated by Benzyltriethylammonium Tetrathiomolybdate in a Multi-Step Tandem Process

The synthesis of a wide range of ferrocene-derived sulfur-linked mono- and disubstituted Michael adducts and conjugates mediated by benzyltriethylammonium tetrathiomolybdate (1) in a tandem process is reported. New route to access acryloylferrocene (4) and 1,1'-diacryloylferrocene (5) is discussed. Conjugation of amino acids to ferrocene is established via their N and C termini and also via side chains employing conjugate addition as key step to furnish mono-and divalent conjugates. This methodology has also been extended to access several ferrocene-carbohydrate conjugates. The electrochemical behavior of some selected ferrocene conjugates was studied by cyclic voltammetry.

Synthesis based on cyclohexadienes. Part 34. A tandem cationic rearrangement-ene cyclisation route to 2-pupukeanone

A new strategy for the construction of the isotwistane skeleton is reported from easily available cyclohexadienes, which involves a one-pot cationic skeletal rearrangement and ene cyclisation of a bicyclo[2.2.2]octenone derivative and a cationic rearrangement of a tricyclo[5.3.0.0(4,8)]decane to a [4.3.1.0(3,7)]decane skeleton as the key steps in the synthesis of 2-pupukeanone.

Tandem Michael reaction. Synthesis of bridged diketones

Addition of NaOMe, NaOEt, or NaOPr(i) to dispironaphthalenone 1 resulted in the formation of diketones 4a-c and 5a-c. The structure assigned to 4a was confirmed by conversion to the known hemiacetal 3. Similar addition of carbon nucleophiles like diethyl malonate, dimethyl malonate, methyl cyanoacetate, and ethyl cyanoacetate afforded diketones 4d-g. Formation of these compounds has been rationalized.

Tandem 5-exo-trig allyl and 3-exo-trig radical cyclisation and rearrangement to copa and ylanga type sesquiterpene skeleton

A novel tandem 5-exo-trig allyl and 3-exo-trig radical cyclisation and rearrangement to copa and ylanga type sesquiterpene skeleton is reported.

Enantiospecific synthesis of functionalised bicyclo[3.3.1] nonanes from 10-bromocarvones via tandem intermolecular alkylation-intramolecular Michael addition sequence

A simple and convenient tandem methodology for the enantiospecific generation of functionalised bicyclo[3.3.1] nonanes 9,14-18, via intermolecular alkylation of Michael donors with 10-bromocarvones 7, 10 and 11, followed by intramolcular Michael addition, is achieved. An unsuccessful attempt for the extension of the methodology for a possible short enantiospecific approach to AB-ring system 22 of taxanes via the allyl bromide 21, is also described.

Structure of tandem and its implication for bifunctional intercalation into dna

Quinoxaline antibiotics (Fig. 1a, b) form a useful group of compounds for the study of drug–nucleic acid interactions1,2. They consist of a cross-bridged cyclic octadepsipeptide, variously modified, bearing two quinoxaline chromophores. These antibiotics intercalate bifunctionally into DNA2,3 probably via the narrow groove, forming a complex in which, most probably, two base pairs are sandwiched between the chromophores4,5. Depending on the nature of their sulphur-containing cross-bridge and modifications to their amino acid side chains, they display characteristic patterns of nucleotide sequence selectivity when binding to DNAs of different base composition and to synthetic polydeoxynucleotides4,6,7. This specificity has been tentatively ascribed to specific hydrogen-bonding interactions between functional groups in the DNA and complementary moieties on the peptide ring2,4,5. Variations in selectivity have been attributed both to changes in the conformation of the peptide backbone6 and no modifications of the cross-bridge7. These suggestions were made, however, in the absence of firm knowledge about the three-dimensional structure and conformation of the antibiotic molecules. We now report the X-ray structure analysis of the synthetic analogue of the antibiotic triostin A, TANDEM (des-N-tetramethyl triostin A) (Fig. 1c), which binds preferentially to alternating adenine-thymine sequences7. The X-ray structure provides a starting point for exploring the origin of this specificity and suggests possible models for the binding of other members of the quinoxaline series.

Features of a unique intronless cluster of class I small heat shock protein genes in tandem with box C/D snoRNA genes on chromosome 6 in tomato (Solanum lycopersicum)

Physical clustering of genes has been shown in plants; however, little is known about gene clusters that have different functions, particularly those expressed in the tomato fruit. A class I 17.6 small heat shock protein (Sl17.6 shsp) gene was cloned and used as a probe to screen a tomato (Solanum lycopersicum) genomic library. An 8.3-kb genomic fragment was isolated and its DNA sequence determined. Analysis of the genomic fragment identified intronless open reading frames of three class I shsp genes (Sl17.6, Sl20.0, and Sl20.1), the Sl17.6 gene flanked by Sl20.1 and Sl20.0, with complete 5' and 3' UTRs. Upstream of the Sl20.0 shsp, and within the shsp gene cluster, resides a box C/D snoRNA cluster made of SlsnoR12.1 and SlU24a. Characteristic C and D, and C' and D', boxes are conserved in SlsnoR12.1 and SlU24a while the upstream flanking region of SlsnoR12.1 carries TATA box 1, homol-E and homol-D box-like cis sequences, TM6 promoter, and an uncharacterized tomato EST. Molecular phylogenetic analysis revealed that this particular arrangement of shsps is conserved in tomato genome but is distinct from other species. The intronless genomic sequence is decorated with cis elements previously shown to be responsive to cues from plant hormones, dehydration, cold, heat, and MYC/MYB and WRKY71 transcription factors. Chromosomal mapping localized the tomato genomic sequence on the short arm of chromosome 6 in the introgression line (IL) 6-3. Quantitative polymerase chain reaction analysis of gene cluster members revealed differential expression during ripening of tomato fruit, and relatively different abundances in other plant parts.

Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Olanzapine in Human Urine

A sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method was developed to determine olanzapine (OLZ) in human urine. After solid-phase extraction with SPE cartridge, the urine sample was analysed on a C-18 column (Symmetry 3.5 mu m, 50 x 4.6 mm i.d) interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase consisted of ammonium acetate (pH 7.8)-acetonitrile (10:90, v/v). The method was linear over a concentration range of 1-100 ngml(-1). The lower limit of quantitation was 1 ngml(-1). The intra-day and inter-day relative standard deviation across three validation runs over the entire concentration range was < 11.5 %. The accuracy determined at three concentrations (8.0, 50.0 and 85.0 ngml(-1) OLZ) was within +/- 1.21 % in terms of relative errors.

Bromenium-Catalysed Tandem Ring Opening/Cyclisation of Vinylcyclopropanes and Vinylcyclobutanes: A Metal-Free 3+2+1]/4+2+1] Cascade for the Synthesis of Chiral Amidines and Computational Investigation

We present a detailed study of a 3+2+1] cascade cyclisation of vinylcyclopropanes (VCP) catalysed by a bromenium species (Brd+?Xd-) generated in situ, which results in the synthesis of chiral bicyclic amidines in a tandem one-pot operation. The formation of amidines involves the ring-opening of VCPs with Br?X, followed by a Ritter-type reaction with chloramine-T and a tandem cyclisation. The reaction has been further extended to vinylcyclobutane systems and involves a 4+2+1] cascade cyclisation with the same reagents. The versatility of the methodology has been demonstrated by careful choice of VCPs and VCBs to yield bicyclo4.3.0]-, -4.3.1]- and -4.4.0]amidines in enantiomerically pure form. On the basis of the experimental observations and DFT calculations, a reasonable mechanism has been put forth to account for the formation of the products and the observed stereoselectivity. We propose the existence of a p-stabilised homoallylic carbocation at the cyclopropane carbon as the reason for high stereoselectivity. DFT studies at B3LYP/6-311+G** and M06-2X/6-31+G* levels of theory in gas-phase calculations suggest the ring-opening of VCP is initiated at the p-complex stage (between the double bond and Br?X). This can be clearly perceived from the solution-phase (acetonitrile) calculations using the polarisable continuum model (PCM) solvation model, from which the extent of the ring opening of VCP was found to be noticeably high. Studies also show that the formation of zero-bridge bicyclic amidines is favoured over other bridged bicyclic amidines. The energetics of competing reaction pathways is compared to explain the product selectivity.

Regioselective Synthesis of Vinyl Halides, Vinyl Sulfones, and Alkynes: A Tandem Intermolecular Nucleophilic and Electrophilic Vinylation of Tosylhydrazones

A diazo species is trapped in an intermolecular fashion by two independent ion species in tandem at the carbene center to install an electrophile and a nucleophile on the same carbon. This metal-free concept, which is unprecedented, has been illustrated by regioselective synthesis of a variety of vinyl halides, vinyl sulfones, and alkyne derivatives.