Synthesis of ansamycins: An approach to the naphthoquinone portion of the rifamycins and streptovaricins

Naphthoquinone $\text{1}$, a fully functionalized model for intermediates in ansamycin synthesis, was prepared by the intramolecular Claisen condensation of benzofuran $\text{9}$ followed by oxidation of the novel tricyclic compound $\text{10}$.     

An approach to mimicking the sesquiterpene cyclase phase by nickel-promoted diene/alkyne cooligomerization

Artificially mimicking the cyclase phase of terpene biosynthesis inspires the invention of new methodologies, since working with carbogenic frameworks containing minimal functionality limits the chemist's toolbox of synthetic strategies. For example, the construction of terpene skeletons from five-carbon building blocks would be an exciting pathway to mimic in the laboratory. Nature oligomerizes, cyclizes, and then oxidizes γ,γ-dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) to all of the known terpenes. Starting from isoprene, the goal of this work was to mimic Nature's approach for rapidly building molecular complexity. In principle, the controlled oligomerization of isoprene would drastically simplify the synthesis of terpenes used in the medicine, perfumery, flavor, and materials industries. This article delineates our extensive efforts to cooligomerize isoprene or butadiene with alkynes in a controlled fashion by zerovalent nickel catalysis building off the classic studies by Wilke and co-workers.     

The shortest synthetic route to puromycin analogues using a modified Robins approach

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.     

An approach to triquinane synthesis using the Pauson-Khand reaction

Tricyclic skeletons have been generated from acyclic enyne precursors by using an intramolecular Pauson-Khand reaction in combination with aldol, Michael and alkylation reactions.     

A new approach to promoting sluggish Diels-Alder reactions: dihapto-coordination of the diene

The cycloaddition between 1,3-cyclohexadiene and various enones and enals (methyl vinyl ketone, ethyl vinyl ketone, methacrolien) is accomplished at room temperature in yields ranging from 51 to 68% without the use of Lewis acids, high pressures, or microwave reactors. This normally sluggish cyclization is accomplished by precoordination of the diene to a pi-basic molybdenum complex. The eta2-bound metal is thought to promote a Michael reaction between the uncoordinated portion of the diene and the enone, and the resulting enolate then closes to form the cycloalkene product. The organic cycloadduct is removed by oxidation with air or with silver triflate in nearly quantitative yield. For more sterically hindered enones (e.g., mesityl oxide) and for methyl acrylate, the desired outcome requires the use of BF3.OEt2, and yields are significantly lower (15-35%)     

An efficient one-pot approach to phenanthrene derivatives using a catalyzed tandem Ullmann-pinacol coupling reaction

In the presence of catalyst (Ph₃P)₂NiCl₂ and reductant Zn, the Ullmann reactions of ortho-halo aryl aldehydes generate biaryl-dialdehydes and zinc halides. Subsequently, ZnX₂ can catalyze the intramolecular pinacol coupling reaction of biaryl-dialdehydes to form 9,10-dihydrophenanthrene-9,10-diols. One-pot synthesis of 9-phenanthrols can be achieved using this strategy.     

An empirical approach to estimation of critical energies by using a quadrupole ion trap

A simple energy-resolved mass spectrometric technique is described for the estimation of critical energies for dissociation of ions via threshold collisional activation measurements in a quadrupole ion trap. The method is calibrated by using compounds with well-defined dissociation energies, and separate calibration curves must be constructed for radical ions that are bound by covalent bonds versus hydrogen-bonded complexes. For these sets of experiments, the threshold point is defined as the activation voltage required for the fragment ion intensity to be 10% of the total ion intensity. A plot of threshold activation voltage of the calibrant versus literature critical energies shows a near-linear function, and accuracies are estimated as better than ± 6 kcal/mol. The q _z value during activation seems to have little effect on the threshold voltages as long as very low q _z values that cause ion ejection are avoided. Activation periods that are substantially longer than 10-ms result in nonlinear behavior in the calibration curves for ions that have critical energies above 30 kcal/mol. This energy-resolved method was also useful for the estimation of critical energies of complexes bound by electrostatic forces, such as hydrogen-bonding interactions. A quantitative evaluation of proton-bound polyether-amine complexes showed that the number of available hydrogen-binding sites, the gas-phase basicities of the polyether and amine components, and the ability of the complex to attain the most favorable near-linear hydrogen bonds correlate with the threshold values.     

An approach for disaccharide chiron synthesis using a Ferrier-type rearrangement

We report a new approach for the synthesis of new chiral synthons in which two unsaturated sugars are linked via a glycosidic bond. The di-unsaturated disaccharide can be further functionalized using effective, highly selective methods and used in convergent syntheses of relatively complex glycoconjugates. Our approach utilizes in situ generation of active glycosyl donors via Ferrier-type rearrangement under phase-transfer conditions and subsequent reaction with a nucleophile.     

A systematic SAR study of C10 modified paclitaxel analogues using a combinatorial approach

A library with 63 paclitaxel analogues modified at the C10 position of paclitaxel has been prepared using parallel solution phase synthesis. Most of the C10 analogues were slightly less active than paclitaxel in the tubulin assembly assay and had reduced potency in the B16 melanoma and MCF-7 cell line cytotoxicity assays. These modifications at C10, however, did not lead to the total loss of activity, indicating that the C10 moiety of paclitaxel may not be directly involved in the drug-microtubule interactions, but could influence its binding affinity to P-glycoprotein. Approximately 50% of the analogues demonstrated better activity against the drug resistant cell line MCF7-ADR. However, the increase in activity was 10-fold at most. This result demonstrates that the cytotoxicity against this drug resistant cancer cell line is sensitive to structural changes at the C10 position of paclitaxel. It was also found that the presence of a nitrogen atom in the C10 substituent might play a role in the interaction of analogues with microtubules.     

An expedient approach to allenes and polycyclic structures using propargyl radicals

A general approach to the synthesis of allenes and polycyclic structures has been developed, based on the addition of a xanthate to an enyne followed by ring-closure of the allenyl radical on to an internal olefin.     

An approach to the isoschizozygane alkaloid core using a 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine

[reaction: see text] A new strategy for the synthesis of the isoschizozygane alkaloid core has been developed that is based on a 1,4-dipolar cycloaddition reaction of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes loss of COS, and further reduction delivers a 5a-aza-acenaphthylene intermediate that was transformed into the isoschizozygane skeleton upon treatment with acid.     

Demetalization of oils resulting from recycled tires by liquid-liquid extraction using modified superheated water An environmentally friendly approach

An approach based on continuous pressurized liquid-liquid extraction with 20% HNO₃/1 M KCl/10⁻³ M EDTA as extractant has been developed for the extraction of metals from the oil resulting from recycled tires. A multivariate optimization of the main variables affecting the extraction process has been performed. The method has been applied to three oil samples with different contents in V, Ni, Zn, Fe and Cu. The target metals have been determined in both untreated and treated oil by flame atomic absorption spectrometry (FAAS) in order to obtain the extraction efficiency. Under the optimum conditions, recoveries higher than 90% have been obtained with a repeatability and within-laboratory reproducibility, expressed as relative standard deviations, ranging from 2.75 to 6.91 and 2.97 to 8.16%, respectively. For applications where the demetalization does not require being complete, a study of the demetalization degree achieved depending on the extraction temperature and extractant composition has also been performed. This study provides useful data about the cheapest working conditions to be used in order to obtain a given demetalization level.     

An approach to thermodynamics

Suggestions are given for a new method of teaching thermodynamics starting from a minimum knowledge of quantum mechanics. For didactical reasons much reference is made to systems having only two energy levels in order to minimise difficulties in understanding the concepts of equilibrium and non-equilibrium.     

An approach to oxasteroids

A tandem Dotz-Mitsunobu sequence has been used to prepare the oxasteroid skeleton     

An approach to compatible multiple nonlinear vibrational spectroscopy measurements using a commercial sum frequency generation system

In this paper, we designed a compatible multiple nonlinear vibrational spectroscopy system that can be used for recording infrared-visible sum frequency generation vibrational spectra (SFG) and infrared-infrared-visible three-pump-field four-wave-mixing (IIV-TPF-FWM) spectra using a commercial EKSPLA SFG system. This is the first time IIV-TPF-FWM signals were obtained using picosecond laser pulses. We have applied this compatible system to study the surface and vibrational structures of riboflavin molecules (also known as vitamin B2). The SFG spectra of eight polarization combinations have non-vanishing signals. The signals with incoming s-polarized IR are relatively weaker than the signals with incoming p-polarized IR. Under the double resonant conditions, the SFG signals of the conjugated tricyclic ring are greatly enhanced. For the IIV-TPF-FWM spectra with incoming p-polarized IR, only the sspp and pppp polarization combinations have non-vanishing signals. The IIV-TPF-FWM spectra show a very strong peak at 1585 cm(-1) that is mainly dominated by the N(5)-C(4a) stretch. The method developed in this study will be helpful for researchers, either using a home-built or commercial (EKSPLA) SFG system, to obtain independent and complementary measurements for SFG spectroscopy and more detailed structural information of interfacial molecules.     

An approach to skeletal diversity using functional group pairing of multifunctional scaffolds

Diversification of enantioenriched Michael adducts through functional group pairing to gain access to a range of five- to ten-membered complex fused and bridged ring systems is described.     

An approach to 2-cyanopyrrolidines bearing a chiral auxiliary

The reaction of 2-methyl-2-((1-phenylethyl)amino)propanenitrile with different γ-halocarbonyl compounds is investigated. The influence of different parameters such as the nature of the substrate and solvent, is discussed. The reaction is considered as a convenient route to 2-cyanopyrrolidines in the case of aliphatic γ-halocarbonyl compounds possessing a reasonably reactive carbonyl group. In many cases, the products can be obtained as single enantiomers. It is shown that cyclopropyl ketones can also react with 2-methyl-2-((1-phenylethyl)amino)propanenitrile to give 2-cyanopyrrolidines. A mechanistic scheme is proposed in order to explain the experimental facts observed.     

Temperature dependent energies of formation for hydrogen-bonded water clusters using a modified mndo and a statistical mechanics approach

Employing a modified MNDO treatment, the hydrogen-bond energies of large water clusters are computed. Considering a statistical mechanical treatment in association with the computed results, an expression of temperature dependent formation energy for water clusters to treat varying conditions of temperature and ambient humidities is introduced. Encouragingly, predicted formation energies (energies of formation) are found to be well correlated with the classical theory of capillarity approximation for the Gibbs free energy change. Based on the predicted energies of formation, stability of water clusters is discussed as a function of cluster size.     

An example of a novel synthetic approach to alkenylpyrroles

The synthesis of 2-methyl-3-(2-propenyl)pyrrole ($\text{2}$) and E- and Z-2-methyl-3-(1-propenyl)pyrroles ($\text{3}$) via the reaction of 3-butenyl methyl ketoxime ($\text{1}$) with acetylene in the KOH-DMSO system is reported.