Irina Novosjolova

User Friendly Synthesis of Vogel’S Silyl Sulfinate and its Application in Quantitative Gc–Ms Analysis

GRAPHICAL ABSTRACT Abstract The synthesis of trimethylsilyl 2-methylprop-2-ene-1-sulfinate (Vogels silyl sulfinate) from methallyltrimethylsilane and SO2 in the presence of Tf2NTMS was developed. The title compound silylates carbohydrates and other polyhydroxylated compounds by producing SO2 and isobutene as gaseous side products. This silylation procedure is perfectly suitable for derivatization and subsequent GC–MS quantitative analysis of ribose and malic acid as representatives of organic polyhydroxylated compounds.

Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-sulfinates in Preparative Silylation and GC-Derivatization Reactions of Polyols and Carbohydrates.

Trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, and triisopropylsilyl 2-methylprop-2-ene-1-sulfinates were prepared through (CuOTf)2⋅C6H6-catalyzed sila-ene reactions of the corresponding methallylsilanes with SO2 at 50 °C. Sterically hindered, epimerizable, and base-sensitive alcohols gave the corresponding silyl ethers in high yields and purities at room temperature and under neutral conditions. As the byproducts of the silylation reaction (SO2 +isobutylene) are volatile, the workup was simplified to solvent evaporation. The developed method can be employed for the chemo- and regioselective semiprotection of polyols and glycosides and for the silylation of unstable aldols. The high reactivity of the developed reagents is shown by the synthesis of sterically hindered per-O-tert-butyldimethylsilyl-α-D-glucopyranose, the X-ray crystallographic analysis of which is the first for a per-O-silylated hexopyranose. The per-O-silylation of polyols, hydroxy carboxylic acids, and carbohydrates with trimethylsilyl 2-methylprop-2-ene-1-sulfinate was coupled with the GC analysis of nonvolatile polyhydroxy compounds both qualitatively and quantitatively.

Structural characterization of cevimeline and its trans-impurity by single crystal XRD.

Cevimeline is muscarinic receptor agonist which increases secretion of exocrine glands. Cevimeline base is a liquid (m.p. 20-25 °C) at ambient conditions, therefore its pharmaceutical formulation as a solid hydrochloride hemihydrate has been developed. The synthesis of cevimeline yields its cis- and trans-isomers and only the cis-isomer is recognized as the API and used in the finished formulation. In this study structural and physicochemical investigations of hydrochloride hemihydrates of cis- and trans-cevimelines have been performed. Single crystal X-ray analyses of both cis- and trans-isomers of cevimeline are reported here for the first time. It was found that the cis-isomer, the API, has less dense crystal packing, lower melting point and higher solubility in comparison to the trans-isomer.

Synthesis of Novel 2- And 6-Alkyl/Arylthiopurine Derivatives

GRAPHICAL ABSTRACT Abstract Synthetic methodologies toward different types of novel 2- and 6-alkyl/arylthiopurine nucleosides, including those containing 1,2,3-triazolyl moieties, are described. The title compounds were obtained by SNAr reactions between 2,6-diazido-, 2,6-dichloro- and 2,6-bis-triazolylpurine nucleosides and different S-nucleophiles. The chemical reactivity of the aforementioned variously substituted purine nucleosides toward different S-nucleophiles is discussed. The obtained monoazido purine nucleoside intermediates exist in azide and tetrazole tautomeric forms. These compounds were later used in 1,3-dipolar cycloaddition reactions with different terminal alkynes. The obtained sulfur-containing nucleoside analogs are interesting in terms of medicinal chemistry.

2,6-Di­chloro-9-(2′,3′,5′-tri-O-acetyl-β-d-ribo­furanos­yl)-9H-purine

The title synthetic analog of purine nucleosides, C16H16Cl2N4O7, has its acetylated β-furanose ring in a 3′β-envelope conformation, with the corresponding C atom deviating by 0.602 (5) Å from the rest of the ring. The planar part of the furanose ring forms a dihedral angle of 65.0 (1)° with the mean plane of the purine bicycle. In the crystal, molecules form a three-dimensional network through multiple C—H⋯O and C—H⋯N hydrogen bonds and C—H⋯π interactions.