Synthesis of (±)-phthalascidin 650 analogue: new synthetic route to (±)-phthalascidin 622

A synthesis of functionalized phenolic α-amino-alcohol (±)-13 as synthetic precursor of the catechol tetrahydroisoquinoline structure of phthalascidin 650 is disclosed. Starting from 3-methylcatechol 5, eight steps of synthesis give rise to the synthesis of phenolic α-amino-alcohol (±)-13 in 27% overall yield. This synthetic strategy involves the elaboration of fully functionalized aromatic aldehyde 8 and its transformation into a phenolic α-amino-alcohol (±)-13, through a Knoevenagel condensation, simultaneous reduction of nitroketene and ester functions and hydrogenolysis of the benzyl protecting group. The pentacycle (±)-18 was obtained after four additional steps. The Pictet-Spengler cyclisation between the phenolic α-amino-alcohol (±)-13 and N-protected α-amino-aldehyde 4 allowed to obtain (1,3′)-bis-tetrahydroisoquinoline 14 with N-methylated and N-Fmoc removed. The last step was a Swern oxidation for allowing an intramolecular condensation.     

Synthesis of (±)-phthalascidin 622

A synthesis of functionalized phenolic α-amino-alcohols (±)-8 and (±)-16 as synthetic precursors of the catechol tetrahydroisoquinoline structure of phthalascidin 650 was disclosed. (±)-8 was prepared in 5 steps from the commercially available sesamol. Starting from 3-methyl catechol 5, 8 steps gave rise to the synthesis of phenolic α-amino-alcohol (±)-16 in 27% overall yield. This synthetic strategy involved the elaboration of fully functionalized aromatic aldehyde 13 and its transformation into a phenolic α-amino-alcohol (±)-16, through a Knoevenagel condensation, simultaneous reduction of nitroketene and ester functions, and hydrogenolysis of the benzyl protecting group. The pentacycle (±)-4 was obtained after 4 additional steps. The Pictet-Spengler cyclisation between the phenolic α-amino-alcohol (±)-16 and the N-protected α-amino-aldehyde 4 allowed to obtain (1,3′)-bis-tetrahydroisoquinoline 17 with N-methylated and N-Fmoc removed. The last step was a Swern oxidation allowing the expected intramolecular condensation.     

Use of organic solvent to prevent protein adsorption in CE-MS experiments

Protein adsorption onto capillary wall often hampers CE separations, particularly in the CZE mode. Electrostatic interactions are not the only factors affecting adsorption, as hydrophobic interactions and/or protein conformational changes are also involved in the adsorption phenomenon. Numerous methods can be used to reduce or avoid adsorption, such as (i) addition of low molecular weight molecules in the BGE, (ii) use of surfactants, or (iii) capillary coatings. However, most of these methods are not MS-compatible. In this study, we evaluated the addition of organic solvent as an alternative MS-compatible method to decrease protein adsorption. The effect of the solvent addition was emphasized using classical methods for estimating reversible and irreversible adsorption. In many cases, organic solvents were effective at decreasing adsorption. However, the influence of the organic solvent on protein adsorption should be evaluated case-by-case in CE method development.     

Polypeptide hybrid copolymers as selective micellar nanocarriers in nonaqueous media

The self-assembly of polystyrene-block-poly(l-lysine) (PS-PLLys·HCl) copolymers with different block lengths has been studied in toluene. The obtained spherical micelles exhibit size variations upon addition of acids or bases, as indicated by light and neutron scattering studies. It is shown that pyridine induces a shrinking of the polystyrene chains in the corona region of the micelles, decreasing the aggregate solvent interface. The addition of benzoic acid, on the other hand, leads to a swelling of the copolymer micelles proportional to the molar fraction of polypeptide. This behavior suggests a selective permeability of the PS-PLLys micelles and the possibility to encapsulate organic compounds in toluene depending on their chemical nature.     

Tin(IV) triflimidate-catalyzed cyclization of epoxy esters to functionalized δ-hydroxy-γ-lactones

In the presence of 5 mol % of tin(IV) triflimidate, a cyclization reaction of epoxyesters to δ-hydroxy-γ-lactones proceeding in 46-98% yields without additives, ligands, or co-catalysts was observed. The cyclization to five-membered rings is greatly favored compared to the possible six-membered rings formation and is probably under the control of a Thorpe-Ingold type effect.     

Dimorphic forms of 3,6‐dinitrodurene in a single space group

3,6‐Dinitrodurene (1,2,4,5‐tetramethyl‐3,6‐dinitrobenzene), C₁₀H₁₂N₂O₄, has been crystallized in two polymorphic forms which may be distinguished by their colours in the solid state. Polymorph I gives clear colourless prismatic crystals, while polymorph II crystallizes in the dark and under an inert atmosphere as irregular purple blocks. Both forms belong to the space group C2/c, with both asymmetric units containing two half‐molecules. One molecule is located on an inversion centre and the other lies on a twofold axis. The polymorphism arises from different orientations of the twofold axis: in form I, this axis passes through the mid‐points of two C—C bonds of the benzene ring and, as a consequence, all atoms in the asymmetric unit are in general positions. In form II, the N atoms of the nitro groups and the C_ipso atoms are located on the binary axis. Comparing phases I and II, slightly different conformations are observed for the nitro substituents, while the stacking structures are very similar.     

Approximate controllability for a system of Schrödinger equations modeling a single trapped ion

In this article, we analyze the approximate controllability properties for a system of Schrödinger equations modeling a single trapped ion. The control we use has a special form, which takes its origin from practical limitations. Our approach is based on the controllability of an approximate finite dimensional system for which one can design explicitly exact controls. We then justify the approximations which link up the complete and approximate systems. This yields approximate controllability results in the natural space (L²(R))²$(L^2{(\mathbb{R}))}^2$ and also in stronger spaces corresponding to the domains of powers of the harmonic operator.     

Cyclic and non cyclic aliphatic–aromatic polyesters derived from biomass: Study of structures by MALDI-ToF and NMR

New polyesters were prepared by polycondensation in solution of 1,4:3,6 dianhydrohexitols with various aliphatic–aromatic acid dichlorides which differ by their chain length (m = 6,8,10). They are obtained with yields in the range of between 89% and 95%. In order to obtain these polymers within optimum conditions, a systematic study was conducted on the effect of the parameters involved in the reaction, such as the alkyl chain length of acid dichlorides and the endo or exo positions of hydroxyl function of diols. The resulting polyesters were characterized by different analytical techniques such as NMR (¹H and ¹³C), FT-IR spectrometry, SEC measurements and MALDI-ToF mass spectrometry. Under optimized conditions a high molar fraction of cyclic polyesters was formed.The differential scanning calorimetry (DSC) measurements revealed an amorphous character with glass transition temperatures in the range of 27–45 °C. The polymers are obtained with inherent viscosities in the range of 0.11–0.25 dL/g with a polydispersity index between 1.75 and 1.99.     

Formation and reactivity of 3-diazopyridinium cations and influence on their reductive electrografting on glassy carbon

The in situ generation of 3-diazonium cations from 3-aminopyridine and their subsequent stability under experimental conditions used for electrografting of pyridine groups were investigated by spectroscopy and electrochemistry. UV spectroscopy revealed the rapid kinetics for the reaction of 3-aminopyridine with sodium nitrite in HCl to form the 3-diazopyridinium cation with a second-order rate constant of 550 ± 20 L mol(-1) s(-1) at 22 °C. UV spectroscopy showed that the 3-diazopyridinium ion was relatively unstable and its transformation into 3-hydroxypyridine was proven by (1)H NMR. Its hydrolytic decomposition was investigated by NMR and followed first-order kinetics with a rate constant of (53 ± 5) × 10(-3) s(-1) at 22 °C. These results enable us to establish the appropriate conditions for the electrografting of pyridine from the corresponding diazonium cations generated in situ. The electrochemical modification of glassy carbon electrodes with pyridine was characterized by cyclic voltammetry and the resulting grafted layer by electrochemical impedance spectroscopy in the presence of Fe(CN)(6)(3-/4-) as redox probes. The effect of diazotization time before electrochemical reduction on the blocking effect of the grafted layer was investigated and showed that an increase of the diazotization time led to less efficient grafting. The presence of immobilized pyridine on the electrode surface was demonstrated by X-ray photoelectron spectroscopy measurements, and a surface coverage of 8.8 × 10(-10) mol cm(-2) was estimated for the grafted pyridine groups. The significance of these results for researchers using the in situ generation approach for electrochemical and chemical grafting is discussed.