Maria J. Milewska

Enantioselective Inclusion Complexation of N‐Nitrosopiperidines by Steroidal Bile Acids

N-nitrosamines, whose chirality is solely due to hindered rotation about the N-N bond, are enantioselectively enclathrated by the crystal host matrices of cholic or deoxycholic acid, as evidenced by X-ray crystallography (see structure in picture) and CD spectra.

Synthesis, stereochemistry, and chiroptical spectra of cyclopropyl lactones and thionolactones

Abstract Several optically active substituted 3-oxabicyclo[3.1.0]hexan-2-ones and their thiocarbonyl analogues were synthesized, and their circular dichroism spectra are reported. It was found that the n-π ∗ Cotton effect sign is determined by the helicity of an inherently chiral chromophore formed by the lactone or thiolactone group and the cyclopropyl moiety. The π-π ∗ Cotton effect of thiocarbonyl compounds shows opposite sign to that observed for the lowest energy transition. The crystal structures of two compounds were solved to establish their molecular geometries.

Conformational properties and chiroptical spectra of lactams and thiolactams with 2-azabicyclo[2.2.1]heptane, 2- and 3-azabicyclo[3.2.1]octane skeletons

Abstract The CD spectra of several bicyclic lactams and thiolactams were measured in different solvents. The concentration dependence of the spectra observed in hydrocarbon solvents was attributed to shifts in the equilibrium between monomer and hydrogen-bonded dimer forms. The CD of some compounds is characterized by unusually strong Cotton effects resulting from non-planarity of the amide bonds due to internal strain of the bicyclic skeletons. The X-ray crystallographic structures of 2a , c , 3b , d and 4a , b showed different degrees of distortion of the amide or thioamide moieties from planarity, which causes inherent chirality of the chromophores and profoundly affects the Cotton effect sign and magnitude. This distortion also restricts application of the sector rules for prediction of the n–π * CD sign, since they can be used only for compounds with planar chromophores.

Synthesis, structure and chiroptical spectra of the bicyclic α-diketones, imides and dithioimides related to santenone

Abstract Isomeric α-diketones, imides and dithioimides related to santenone were prepared in a multistep synthesis from (+)-camphor and their CD spectra compared with those of analogous chromophoric systems related to camphor. In the case of conformationally rigid α-diketones the methyl substituents at C-7, lying on the symmetry plane of the chromophore, exert only a weak contribution to the n–π* Cotton effects. In contrast, the Cotton effect magnitudes of the anhydrides, imides and dithioimides are significantly affected by the substituents at C-8. The steric interaction of these chromophores with the syn -methyl group at C-8, leading to the chromophore distortion, was confirmed by X-ray crystallographic studies.

Synthesis of optically active monothioimides with chirality due to sulphur substitution

Abstract Two optically active bicyclic monothioimides were prepared via chiral derivatives of cis -1,2-cyclopropanedicarboxylic and cis -1,3-cyclopentanedicarboxylic acids and their absolute configurations were assigned.

Chiroptical spectra of bicyclic selenolactams. Optical activity of the singlet–triplet transition

Abstract Two selenolactams with rigid 2-azabicyclo[2.2.1]heptane skeletons were prepared by reaction of the corresponding lactams with P 4 Se 10 . A comparison of their UV–vis and CD spectra with those of the carbonyl and thiocarbonyl analogues showed a similar character of the lowest-energy electronic transitions and the same signs of the corresponding Cotton effects. The MCD spectra of selenolactams revealed that their n–π* absorption band is dominated by the singlet–triplet component. A very weak CD corresponding to this component has an opposite sign to its much stronger singlet–singlet counterpart observed at the blue edge of the n–π* band.

Antifungal Activity of Homoaconitate and Homoisocitrate Analogs

Thirteen structural analogs of two initial intermediates of the l-α-aminoadipate pathway of l-lysine biosynthesis in fungi have been designed and synthesized, including fluoro- and epoxy-derivatives of homoaconitate and homoisocitrate. Some of the obtained compounds exhibited at milimolar range moderate enzyme inhibitory properties against homoaconitase and/or homoisocitrate dehydrogenase of Candida albicans. The structural basis for homoisocitrate dehydrogenase inhibition was revealed by molecular modeling of the enzyme-inhibitor complex. On the other hand, the trimethyl ester forms of some of the novel compounds exhibited antifungal effects. The highest antifungal activity was found for trimethyl trans-homoaconitate, which inhibited growth of some human pathogenic yeasts with minimal inhibitory concentration (MIC) values of 16–32 μg/mL.

Stereochemistry and chiroptical spectra of 3-azabicyclo[3.1.0]hexan-2-ones and thiones

Abstract Several optically active substituted 3-azabicyclo[3.1.0]hexan-2-ones and their thiocarbonyl analogues have been synthesized, and their circular dichroism spectra studied. The crystal structure of thiolactam 1a showed that the bicyclic skeleton of the title compounds assumes a sofa-like geometry. It is postulated that the cyclopropyl moiety and amide or thioamide group constitute an inherently chiral chromophore, helicity of which determines the Cotton effect sign corresponding to the n -π ∗ electronic transition. The weak π-π ∗ Cotton effect of thiolactams shows opposite sign to that observed for the lowest energy excitation.

N-Hydroxyamino Acids and Their Derivatives

N-Hydroxyamino acids should, at present, be treated as a new, separate, characteristic group of amino acids. This is necessitated by the particular biological action of these compounds and their derivatives. Although α-N-hydroxyamino acids were first discovered by Miller and Plochl (1) as early as 1893, they have aroused particular interest mainly in the last twenty years.

Oxidation of amino acid. Part V. A novel synthesis of N6-Acetyl-N6-hydroxylysine from lysine

Abstract N 6 -Acetyl-N 6 -L-hydroxylysine was synthesized from L-lysine by oxidation of the amino group in the N 2 -benzyloxycarbonyl-L-lysine tert- butyl ester with benzoyl peroxide and subsequent acetylation.