Helvetica Chimica Acta最新文献

An improved, scalable, industrially feasible telescopic process for multigram synthesis of highly commercialized antidepressant drug, moclobemide has been developed. Unlike the conventional approaches, this process enjoys the privilege of being an economical, operationally simple, effectively scalable, and quantitative method for the synthesis of amide-containing drug moclobemide, showcasing easy isolation and purification without the aid of column chromatography. An environmentally benign reagent combination of TBN and NHS very effectively converts the acyl source, 4-chlorobenzaldehyde into its N-hydroxysuccinimide ester intermediate, which simply affords the drug molecule after nucleophilic substitution with the amine source. The synthetic process has successfully been scaled-up upto ~145 g scale with 75 % overall yield and >95 % first crop HPLC purity.

Herein, we report a new method for the synthesis of functionalized pyrrole and isoquinoline derivatives using isoxazole based precursors. The reaction proceeds through the ring opening and ring closing cascade mechanism (ROCC) to afford pyrrole or isoquinoline derivatives in good to excellent yields under very mild experimental conditions. Product outcome relies on the strategic placement of different substituents on the isoxazole moiety. The present method is also applicable to synthesize functionalized isoquinolone derivatives.

Positron Emission Tomography (PET) is an important part of the medical imaging field which is continually exploring novel biological targets as exemplified by PET imaging of neuroinflammation. Due to limitations stemming from either sub-optimal biological targets or a lack of available selective radiotracers, alternative biomarkers and PET imaging agent candidates are considered. One such possible target is microRNA (miRNA) and herein, we discuss the potential of miRNA for PET imaging. With the aim of addressing key strategies for imaging miRNA with PET, we identify three distinct approaches as follows: small molecules directly targeting miRNA, small molecules indirectly targeting Argonaute 2 (AGO2)-protein complexes, and direct chemical modification of antisense oligonucleotides. The radiosynthetic approaches are based on the methods of direct radiolabelling of respective antisense oligonucleotides and several examples are described herein, showcasing the potential of miRNA in PET imaging. Whilst these approaches offer different radiolabelling strategies, application of these radiolabelled molecules towards PET imaging of miRNA are scarce with only one, limited example applied to bone remodeling reported in the literature.

Herein we report a platinum-catalyzed isomerization of cyclopropenes to 1,3-dienes. Diverse dienylated alcohols were obtained in 42–98 % yield. The synthetic potential of the products was demonstrated by their use in Diels–Alder cycloadditions with various dienophiles. Isotope labelling studies provide strong support for a mechanism involving pericyclic [1,5]-σ-bond rearrangement of a vinyl platinum carbene intermediate.

The paramagnetic osmium(III) [Os(SR_F)(S₂CNEt₂)₂(P(C₆H₄X-4)₃)] (R_F=C₆F₄H−4, C₆F₅; X=OCH₃, CH₃, F) (1–6) along with diamagnetic osmium(IV) [Os(SR_F)₂(S₂CNEt₂)₂] (7–8) complexes were obtained from [Os(SR_F)₄(P(C₆H₄-X)₃)] and NaS₂CNEt₂, which were characterized by FAB mass spectrometry, IR spectroscopy, single crystal X-ray diffraction, and for the diamagnetic 7 also by NMR. TD-DFT calculations were performed to simulate the absorption spectra of complexes. In the visible region, LMCT transitions contribute to the calculated intensities, which are somewhat related to the color of the synthesized compounds. In the ultraviolet region, the phosphine ligand plays a significant role in MLCT transitions, which results in Os(III) complexes exhibiting an intense band in that region. Topological analysis and electron localization function (ELF) maps calculated for 6 and 7 confirm the strong ionic character of the Os−S coordination bonds formed by the thiophenolate and dithiocarbamate ligands. This comprehensive study provides information on the structure, bonding, and electronic properties of osmium complexes, for potential applications in catalysis, materials science, and biological systems.

The prevalence of quaternary stereogenic centers in bioactive molecules coupled with innate challenges associated with their enantioselective preparation continues to provide powerful impetus for the development of catalytic asymmetric methods capable of their construction. Herein, we describe a cooperative isothiourea Lewis base-palladium catalyst system that enables the enantioselective alkylation of α-substituted-α-cyano esters with allyl methanesulfonate. While the levels of enantioselection are modest, this study represents the first time we have successfully constructed quaternary-substituted stereogenic centers using this Lewis base-palladium cooperative catalysis scheme. Further, this strategy constitutes a departure from ligand-based enantiocontrol and suggests that, when using acidic pro-nucleophiles, the development of protocols where Lewis base catalysis can outcompete direct deprotonation might be within reach.

Amines, crucial components in various industries, play a pivotal role in the synthesis of pharmaceuticals, agrochemicals, and specialty chemicals. Recognizing the environmental impact of conventional methods for their preparation, our study centers on the utilization of abundantly available natural molecules, specifically amino acids, as precursors for short chain amine synthesis. This paper focuses on the biocatalyst, L-valine decarboxylase from Streptomyces viridifaciens (VlmD), delving into the substrate scope, catalytic activity, and cost-effective scalability of an enzymatic process for amine synthesis. Additionally, we investigate the feasibility of immobilizing VlmD, aiming to pave the way for its effective use in industrial applications. Our study exploits the SpinChem system and provides a comprehensive understanding of the potential and limitations of this biocatalyst. Notably, our yields for key amines (8.42 g ⋅ d⁻¹ for isobutylamine, 5.23 g ⋅ d⁻¹ for isoamylamine, 5.16 g ⋅ d⁻¹ for (S)-2-methylbutylamine, 3.78 g ⋅ d⁻¹ for 3-(methylthio)propylamine, and 10.52 g ⋅ d⁻¹ for (R)-1-amino-2-propanol) demonstrate the process efficiency and potential for industrial scalability.

A novel, industrially viable synthetic route to (+)-biotin has been developed starting from L-cysteine via the known key thiolactone intermediate. The route takes advantage of the in-built stereochemistry of the cysteine starting material and the best features of the two current industrialized processes. The key transformations are the conversion of L-cysteine into a hydantoin avoiding racemization followed by catalytic cyanation and thiolactonization to form the required thiolactone intermediate. This known intermediate can be readily further transformed into (+)-biotin.

Colloidal solutions of gallia-alumina (Ga,Al)₂O_3(x:y) solid-solution nanoparticles with nominal atomic Ga : Al (x:y) ratios of 1 : 6, 1 : 3, 3 : 1, and 1:0 were used to prepare silica-supported catalysts for propane dehydrogenation (PDH). A comparison of the unsupported and silica-supported catalysts reveals that the dispersion on silica increases the Ga-normalized PDH rates for all catalysts, albeit with a notably lower propene selectivity for (Ga,Al)₂O_3(1:6)/SiO₂. Fourier transform infrared (FTIR) spectroscopy allows contrasting the H₂ dissociation sites in the calcined and H₂-treated (Ga,Al)₂O_3(x:y)/SiO₂, indicating a transformation of Ga³⁺ surface sites with Al (mainly) and Ga atoms in the second coordination sphere (Ga_(Al/Ga) sites) in the calcined (Ga,Al)₂O_3(1:6)/SiO₂ to predominantly Ga_(Ga/Si) surface sites in the H₂-treated material. The resulting sites are similarly unselective as in amorphous gallia on silica. H₂ produced during the PDH reaction can cause a similar transformation as H₂ pretreatment in (Ga,Al)₂O_3(1:6)/SiO₂, rapidly resulting in a notably lowered selectivity. The stable and selective Ga_(Al/Ga) surface sites in (Ga,Al)₂O_3(1:3)/SiO₂ yield a Ga−H band at ca. 1990 cm⁻¹ under H₂ dissociation conditions while the less selective surface sites, observed for the other Ga : Al ratios, give Ga−H bands at ca. 2040 and 2060 cm⁻¹.