Ērika Bizdēna

ON DIFFERENCES BETWEEN RACEMIC AND ENANTIOMERICALLY PURE FORMS OF AZIRIDINE-2-CARBOXAMIDE*

Synthesis, X-ray, and cytotoxicity studies of (S)- and (R)-aziridine-2-carboxamide (Leakadine) are described. X-ray data for the enantiomerically pure form are compared with those for racemic aziridine-2-carboxamide in order to explain the 21°C large melting point difference between both series. It was found that despite their overall low cytotoxicity (S)-aziridine-2-carboxamide is slightly more cytotoxic than (R)-aziridine-2-carboxamide.

Structural Proof of Tetrazolo[1,5-a]quinazoline Derivatives and Their Application in the Synthesis of 4-Amino-2-(1,2,3-triazol-1-yl)quinazolines

5-Azidotetrazolo[1,5-a]quinazoline (formally known as 2,4-diazidoquinazoline) undergoes regio-selective nucleophilic aromatic substitution with amines at the C-5 atom and provides corresponding 5-amino derivatives of tetrazolo[1,5-a]quinazoline. For the first time, the molecular structure of the latter tricyclic system is unambiguously proved by X-ray structural analysis. Tautomeric equilibrium between tetrazolo[1,5-a]quinazolines and 2-azidoquinazolines permits their use in the copper- catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction. In this way a series of 4-(R-amino)-2-(1,2,3-triazol-1-yl)quinazolines were obtained.

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.

Synthesis and Antibacterial Activity of 5-Phthalate and 5-Glutarate Derivatives of Milbemycins A 3 /A 4 *

Naturally occurring 16-membered macrolides milbemycins A3 and A4 were selectively esterified at their 5-OH group with phthalic and glutaric anhydrides. The obtained monoesters were further functionalized by amide formation. Propargylamide derivatives were demonstrated to undergo 1,2,3-triazole formation upon treatment with organic azides in the presence of copper catalyst. Some of the synthesized compounds exhibited useful levels of antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis.

Synthesis and Immunological Evaluation of Virus-Like Particle-Milbemycin A3/A4 Conjugates

Milbemycins are macrolide antibiotics with a broad spectrum of nematocidal, insecticidal, and acaricidal activity. To obtain milbemycin A3/A4 derivatives suitable for chemical conjugation to protein carriers (milbemycin haptens), succinate linker and a novel 17-atom-long linker containing a terminal carboxylic acid group were attached to the milbemycin core in a protecting group-free synthesis. The obtained milbemycin A3/A4 derivatives were coupled to Potato virus Y-like nanoparticles by the activated ester method. The reaction products were characterized and used in mice immunization experiments. It was found that the mice developed weak specific immune responses toward all tested milbemycin haptens.

Synthesis of 4-Alkylamino-2-Triazolylquinazolines

Abstract 5-Alkylamino derivatives of tetrazolo[1,5-a]quinazoline were obtained with high regioselectivity in the reaction of 5-azidotetrazolo[1,5-a]quinazoline (formally, 2,4-diazidoquinazoline) with long chain alkylamines. The obtained 5-aminoquinazoline derivatives were used in a copper catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction to obtain series of 4-(alkylamino-2-(1,2,3-triazol-1-yl)quinazolines.

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.

Crystal structure of methanolsodium dianemycin — methanol (1:2), Na(C47H77O14)(CH4O) · 2CH4O

C50H89NaO17, monoclinic, P21 (no. 4), a = 10.1377(2) A, b = 21.3450(3) A, c = 13.2198(3) A, ) = 106.5546(7)°, V = 2742.1 A, Z = 2, Rgt(F) = 0.058, wRref(F ) = 0.166, T = 193 K.