Viktors Kumpiņš

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.

Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester linkage.

Graphical abstract Figure. No Caption available. HighlightsNovel lupane triterpenoid‐indazolone hybrids with oxime linkage are obtained.This is the first report on oxime esters derived from betulonic and betulinic acid at their C(28).X‐ray structure of the hybrid molecule is reported.Purification procedure for betulonic acid via its cyclohexylammonium salt is developed. Abstract An efficient protocol for the synthesis of novel lupane triterpenoid‐indazolone hybrids with oxime ester linkage has been developed from naturally accessible precursor betulin. For the first time a series of betulonic acid‐indazolone hybrids have been synthesized via an acylation of corresponding 6,7‐dihydro‐1H‐indazol‐4(5H)‐one oximes with betulonic acid chloride. Diastereoselective reduction of the obtained betulonic acid conjugates with NaBH4 resulted in a formation of betulinic acid‐indazolone hybrids in excellent yields. The configuration of the key compounds has been fully established by X‐ray and 2D NMR analysis.

X-ray structure analysis of a solid solution of milbemycins A3 and A4

Milbemycins A3 and A4 are pharmaceutically and agriculturally useful macrolides isolated from Streptomyces species. The molecular structures of the title compounds were unambiguously established by a single crystal X-ray analysis of the solid solution of both compounds. The crystals present trigonal system, space group P32 with Z = 3, unit cell dimensions: a = 12.2211(4), c = 17.5372(7) Å; V = 2268.4(1) Å3, μ = 0.082 mm− 1; d = 1.183 g cm− 3. An interesting system of intramolecular hydrogen bonds and weak intermolecular CH…O type hydrogen bond was observed in the solid state.

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 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.

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.