Total synthesis of maremycins A,B, C1/C2, D1, and D2

The total synthesis of maremycins A, B, C₁/C₂, D₁, and D₂ is achieved starting from the natural amino acids l-isoleucine and S-methyl-l-cysteine, in which the total synthesis of maremycins B, C₁/C₂, and D₂ is accomplished for the first time. The synthesis features a position-selective intramolecular bromination process for the synthesis of key chiral building block, a Pd-catalyzed indole synthesis for the preparation of (2S,3S)-β-methyltryptophan and hydroxylation of oxindoles by molecular oxygen. In addition, the protocol for conversion of maremycins A and B to maremycins C and D was improved.     

1,9-Bis(N,N-dimethylaminomethyl)dipyrromethanes in the synthesis of porphyrins bearing one or two meso substituents

A synthesis of 5,15-disubstituted zinc-porphyrins has been developed that employs condensation of a 1,9-bis(N,N-dimethylaminomethyl)dipyrromethane+a dipyrromethane in refluxing ethanol containing zinc acetate followed by oxidation with DDQ. The N,N-dimethylaminomethylation of the dipyrromethane was achieved via Eschenmoser's reagent (N,N-dimethylmethyleneammonium iodide) in CH₂Cl₂ at room temperature. The synthesis is compatible with diverse substituents (e.g., alkyl, aryl, ester, acetal) and enables rapid synthesis of trans-AB-, A₂-, and A-porphyrins. The synthesis of >40 zinc porphyrins has been surveyed; 13 zinc porphyrins were isolated in yields of 5-20% without detectable scrambling.     

Boron trifluoride etherate-assisted ring opening of ethylene oxide by a chiral organolithium: enantioselective synthesis of (R)-N-Boc-2-(2-hydroxyethyl)pyrrolidine

A practical synthesis of (R)-N-Boc-2-(2-hydroxyethyl)pyrrolidine in high enantiomeric purity is described. The synthesis involves BF₃·Et₂O-assisted ring opening of ethylene oxide by a homochiral carbanion (R)-3, which is derived from sparteine-mediated asymmetric deprotonative lithiation of 1-Boc-pyrrolidine.     

A type 2 Ferrier rearrangement-based synthesis of d-myo-inositol 1,4,5-trisphosphate

The synthesis of d-myo-inositol 1,4,5-trisphosphate (InsP₃) from methyl α-d-glucopyranose, via a type 2 Ferrier rearrangement is reported. A key intermediate in this synthesis possesses orthogonal protecting groups at the 1-, 4- and 5-position, making it a versatile starting point for the synthesis of unnatural InsP₃ derivatives. Biological evaluation of the synthetic InsP₃ demonstrates that this compound evokes selective Ca²⁺ release via activation of InsP₃ receptors.     

Catalytic transformations of sulfur dioxide into organic sulfur compounds

The applications of catalytic transformations of SO₂ into sulfur-containing organic compounds, reported in the literature, are briefly reviewed. The authors' studies in this field of chemistry,viz., the hydrosulfination of alkenes, the synthesis of γ-oxo sulfonesvia hydrosulfination, and the synthesis of aromatic sulfinic acids from diazonium salts, are summarized. Current results on the synthesis of the new sulfinato complex [Pd(SO₂Ph)(Cl)dppp] and its hydrogenation to PhSO₂H are presented, and a mechanism for the catalytic synthesis of sulfinic acids is proposed. The structure of ([Pd(μ-Cl)(dppp)l₂ ²⁺(SO₄)^2?·4SO₂ salt is studied by X-ray diffraction analysis.     

Exploiting morph-DAST mediated ring-expansion of substituted cyclic β-amino alcohols for the preparation of cyclic fluorinated amino acids. Synthesis of 5-fluoromethylproline and 5-fluoropipecolic acid

The synthesis of proline analogues bearing a fluorine-containing substituent at the fifth position of the pyrrolidine ring, racemic trans- and cis-5-fluoromethyl prolines, was performed. The key step of the synthesis is a transformation of the CH₂OH-group into the CH₂F-one using morpholinosulfur trifluoride. During the synthesis, an efficient procedure to prepare trans- and cis-5-fluoropipecolic acids was elaborated.     

Olefin metathesis polymerization: Some recent developments in the precise polymerizations for synthesis of advanced materials (by ROMP,ADMET)

Recent results for synthesis of end-functionalized polymers (EFP) by using olefin metathesis polymerization have been introduced including basic characteristics in ring-opening metathesis polymerization (ROMP) of cyclic olefins and acyclic diene metathesis (ADMET) polymerization for synthesis of conjugated polymers. Several approaches were demonstrated for synthesis of EFP by living ROMP using molybdenum (exclusive coupling with aldehyde) and ruthenium catalysts (sacrificial ROMP, chain transfer). Cis specific (Z selective) ROMPs were achieved by molybdenum, ruthenium, and vanadium catalysts by the ligand modification. The catalytic synthesis of EFP with high cis selectivity has been achieved by combined ROMP with chain transfer by V(CHSiMe₃)(N-2,6-Cl₂C₆H₃)[OC(CF₃)₃](PMe₃)₂. The ADMET polymerization using molybdenum and ruthenium catalysts afforded defect-free, high molecular weight poly(arylene vinylene)s containing all trans olefinic double bonds. The methods for precise synthesis of EFPs, exhibiting unique optical properties combined with the end groups, were developed. The catalytic one-pot syntheses for EFPs have also been developed.     

Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2+2’ porphyrin formation reactions is presented.     

A facile one-pot synthesis of 2-fluoroalkyl 1,3-imidazolines and 1,3-oxazolines through imidoyl halide intermediates

A facile one-pot procedure has been developed for the synthesis of 1,3-imidazolines and 1,3-oxazolines bearing fluorinated alkyl groups at the 2-position. The reaction involves the condensation of N-monosubstituted ethane-1,2-diamines or 2-aminoethanols with a fluorinated carboxylic acid in the presence of PPh₃/CX₄. The proposed mechanism is that the amide intermediates were initially formed, and then converted to the imidoyl halide intermediates in the presence of PPh₃/CX₄, followed by rapid intramolecular cyclization to 1,3-diazoline products. This protocol allows for the synthesis of 2-bromodifluoromethyl-1,3-imidazoline, a useful CF₂Br-heterocyclic building block, which can be used for the synthesis of gem-difluoromethylene linked compounds.     

Iron-catalyzed hydroaminocarbonylation of alkynes: Selective and efficient synthesis of primary α,β-unsaturated amides

α,β-Unsaturated primary amides are important intermediates and building blocks in organic synthesis. Herein, we report a ligand-free iron-catalyzed hydroaminocarbonylation of alkynes using NH₄HCO₃ as the ammonia source, enabling the highly efficient and regioselective synthesis of linear α,β-unsaturated primary amides. Various aromatic and aliphatic alkynes are transformed into the desired linear α,β-unsaturated primary amides in good to excellent yields. Further studies show that using NH₄HCO₃ as the ammonia source is key to obtain good yields and selectivity. The utility of this route is demonstrated with the synthesis of linear α,β-unsaturated amides including vanilloid receptor-1 antagonist TRPV-1.     

Diastereoselective synthesis of novel 5-substituted morpholine-3-phosphonic acids: further exploitation of N-acyliminium intermediates

The first diastereoselective total synthesis of 5-substituted morpholine-3-phosphonic acids is reported. The principal feature of the synthesis is the introduction of a dimethyl phosphonate group into 5-substituted morpholin-3-ones. The procedure is based on the preparation of N-Boc-(S)-5-phenyl- and N-Boc-(S)-5-benzylmorpholin-3-one from l-phenylglycine and l-phenylalanine methyl esters, followed by the formation of the 3-methoxylated compounds and subsequent reaction with trimethyl phosphite in the presence of BF₃·OEt₂. Diastereoselectivity in the formation of cis-disubstituted products is in agreement with the nucleophilic addition to other methoxylated derivatives.     

A green route for microwave synthesis of sodium tungsten bronzes NaxWO3 (0<x<1)

A green route has been developed for microwave synthesis of sodium tungsten bronzes Na_xWO₃ (0<x<1) from Na₂WO₄, WO₃ and tungsten powder. The hybrid microwave synthesis was carried out in argon atmosphere using CuO powder as the heating medium. Tungsten powder is used as the reducing agent instead of the alkali metal iodides previously used for the microwave synthesis of oxide bronzes. The prepared samples were characterized by powder X-ray diffraction, energy-dispersive X-ray analysis and scanning electron microscopy, and their phase constitutions, crystal structures and morphologies are in consistence with that in the literature. This synthesis method is simple, green and atom economic, and promising for preparation of other oxide bronzes and related compounds.     

Asymmetric synthesis of l-proline regio- and stereoselectively labelled with deuterium

A synthesis of l-proline where all of the ring methylenes are stereoselectively labelled with deuterium is described. A catalytic deuteration of protected 3,4-dehydro-l-proline using transition metal catalyst followed by RuO₄-oxidation gave a [3,4-D₂]pyroglutamic acid derivative. A syn-selective deuteration of the aminal derived from the pyroglutamate with Et₃SiD–BF₃·OEt₂ furnished (2S,3S,4R,5S)-[3,4,5-D₃]proline. The present procedure is also applied to the synthesis of the corresponding (2S,3S,4R,5R)-isomer.     

Synthesis of desmosine-d4: Improvement of isotopic purity by D-H exchange of amino groups

Desmosine is a crosslinking pyridinium amino acid of elastin, which is a useful biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) by LC–MS/MS analysis. We previously reported a synthesis of desmosine-d₄, which is useful as an internal standard for quantitative LC–MS/MS analysis of desmosines, by deuterogenation of an alkyne group; however, the isotopic purity of the desmosine-d₄ was only ca. 50%. The present report describes a new synthesis of desmosine-d₄ that improves the isotopic purity to ca. 90% by exchanging the protons of the amino groups to deuterium using deuterogenation.     

Synthesis of meso-tetraarylporphyrins using SeO2 as oxidant

The oxidative step of the two-step, one-flask synthesis of meso-tetraarylporphyrins is herein conducted with heterogeneous oxidant SeO₂ instead of the usual quinones DDQ or p-chloranil. Evaluation of BF₃O(Et)₂ or I₂ amount for the condensation of the first step combined with the excess of SeO₂ defined porphyrin synthesis conditions employing benzaldehydes and pyrrole (or 5-phenyldipyrromethane) as starting materials. The simplicity of the workup, allied with reaction mild conditions, makes this method a good option for the synthesis of this kind of compound.     

Synthesis of partially benzylated arabinofuranosides,NMR analysis,and application to oligosaccharide synthesis

The preparation and NMR analysis of 2,3-di-O-benzyl arabinofuranosides have been described. In DMSO-d₆, the sugar adopts a conformation in which the hydroxyl groups are in an equatorial position; the equilibrium composition is determined by steric factors. In CDCl₃, the sugar adopts a conformation in which the intramolecular hydrogen bonding plays an important role in determining the equilibrium composition. The use of 2,3-di-O-benzyl arabinose in the synthesis of oligoarabinofuranosides enabled the synthesis of α- or β-linked furanosides.     

Amino-zinc-ene-enolate cyclisation: a short access to (2S,3R)- and (2S,3S)-3-benzylprolines (3-benzylpyrrolidine-2-carboxylic acids)

The synthesis of 3-benzylprolines can be easily achieved in a diastereoselective and enantioselective way via amino-zinc-ene-enolate cyclisation. Transmetalation of the cyclic zinc intermediate with Pd₂(dba)₃/P(o-Tolyl)₃ allowed functionalisation with an aromatic ring. One-pot hydrogenolysis and Boc-protection led to the cis-isomer readily usable for peptide synthesis. The trans-isomer was obtained by epimerisation of the α-centre in a sealed tube at 200 °C.     

X-Ray and Electron Microscopy Studies of Rare-Earth Tungsten Bronzes

Rare-earth tungsten bronzes, RE_xWO₃, of perovskite tungsten-bronze (PTB) type, formed by conventional solid-state synthesis, have been studied by X-ray powder diffraction, electron diffraction in combination with microanalysis, and high-resolution transmission electron microscopy (HRTEM). The X-ray patterns indicated cubic PTB type structure with a≈3.83 Å (subcell), while the electron microscopy study indicated a lowering of the subcell symmetry and a complex superstructure. The upper phase composition limit, x≤0.25, for the RE_xWO₃ bronzes with PTB-related structures was established from the microanalysis study. Ordered, disordered and microtwinned superstructures were revealed by electron diffraction patterns and HRTEM images taken along 〈110〉_p. The superstructure is due to filling of the interstices in the WO₃ structure with the rare-earth ions. A hypothetical model of the superstructure based on the contrast features in the HRTEM images has been deduced. The relationships between the RE_xWO₃ bronzes formed by solid-state synthesis under high- and ambient-pressure conditions are presented.     

Formation of LiAlyNi1−yO2 solid solutions under high and atmospheric pressure

Three methods were used for the synthesis of LiAl_yNi_1−yO₂ solid solutions with layered crystal structure: citrate and hydroxide precursor methods at atmospheric pressure and high-pressure synthesis in oxygen-rich atmosphere (3 GPa). Structural characterization of the oxides was performed by powder XRD analysis and electron paramagnetic resonance (EPR) spectroscopy. Irrespective of the different preparation techniques used, it was found that LiAl_yNi_1−yO₂ solid solutions can be formed in the limited concentration range of 0?y?0.5 and 0.75?y?1.0. The unit cell parameter a decreases linearly with the Al content whereas the unit cell parameter c increases sharper as compared to the linear interpolation of the c parameter calculated for the two end compositions LiNiO₂ and LiAlO₂. In these compositions, aluminum substitutes for Ni in the NiO₂-layer, the mean Al_yNi_1−y-O bond length decreasing. The extent of the trigonal distortion of Al_yNi_1−yO₆ and LiO₆-octahedra varies with the aluminum content and depends on the synthesis procedure used. The LiO₆-octahedra are more flexible to tolerate the increased trigonal distortion as compared to the Al_yNi_1−yO₆-octahedra. High-pressure synthesis favors the formation of oxides with a higher extent of trigonal distortion of both Al_yNi_1−yO₆ and LiO₆-octahedra. From EPR measurements, it was shown that local cationic distribution in LiAl_yNi_1−yO₂ depends on the synthesis temperature. At atmospheric pressure, higher synthesis temperatures promote the reaction of cation mixing between the layers.     

Investigation for the cyclization efficiency of linear tetrapeptides: Synthesis of tentoxin B and dihydrotentoxin

Investigation of the cyclization efficiency of N-methyl linear tetrapeptides using a molecular modeling study and chemical synthesis is described. The linear peptide with two N-methyl groups, MeAla-Leu-MePhe-Gly, forms γ-turn like conformation with the amine at N-terminus and the carbonyl at C-terminus in closer proximity to give the desired cyclic tetrapeptide, dihydrotentoxin. In addition, synthesis of tentoxin B by the combination of Fmoc solid-phase peptide synthesis and cyclization in solution phase has been reported. An unusual amino acid, an L-N-methyl-β-hydroxyphenylalanine derivative, which was assembled on solid support, was prepared from ethyl cinnamate. Cyclic tetrapeptide formation and cleavage of benzyl ether were optimized with DIPCI/HOBt/DIPEA and Et₃SiH/Pd(OH)₂, respectively.