László F. Szabó

Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine

Strictosidine, the precursor of more than 2,500 indole alkaloids, was isolated from four species of three plant families. By searching the Dictionary of Natural Products on DVD it was found that about 150 indole alkaloids were obtained from the same species (coalkaloids), which is a direct proof of their common origin. On the base of their three-dimensional structure, taxonomic properties and standard reaction mechanisms an extended network was established which involved the four fundamental skeletons, the three types of carbon framework in the secologanin subunit and all major groups of indole alkaloids derived from secologanin and tryptamine (except a few minor groups, in which only less then 10 alkaloids were known). The system was extended to the heterodimer indole alkaloids and the quinoindole alkaloids as well.

Unusual tigliane diterpenes from euphorbia grandicornis

Phytochemical study of the aerial parts of Euphorbia grandicornis led to the isolation of two new tigliane diterpenes, 16-angeloyloxy-13α-isobutanoyloxy-4β,9α,20-trihydroxytiglia-1,5-diene-3,7-dione (1) and 16-angeloyloxy-13α-isobutanoyloxy-4β,9α,7β-trihydroxytiglia-1,5-dien-3-one (2). The structures and relative configuration of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments ((1)H NMR, JMOD, (1)H-(1)H COSY, NOESY, HSQC, and HMBC), mass spectrometry, and comparison with literature data. The biogenesis of 1 and 2 with respect to the unusual 5-en-7-one and 5-en-7-ol moieties is also discussed.

Chemistry of secologanin. Part 7: Chemical fragmentation of secologanin: biomimetic transition from the aliphatic into the aromatic skeleton

Abstract Transformation of secologanin and its ethylene acetal was investigated under acidic and basic conditions. Under acidic conditions both compounds gave benzaldehyde and an undefined fragment. A primary amine was incorporated into the substrate by lactamization with or without deglucosylation. Secondary and tertiary amines catalyzed lactonization of secologanin, but piperidine cleaved the acetal into methyl 3-piperidino-acrylate and an undefined C 7 unit which proved to be a phenyl group analogous to the indole alkaloid derivatives of secologanin. The biogenetic and biomimetic significance of the fragmentation is discussed.

Chemistry of secologanin. Part 5. Graphical analysis of the acidic deglycosylation of vincoside derivatives

Acidic hydrolysis and cyclization were studied in vincoside glycosides (‘natural’ series) and their dihydro derivatives (‘dihydro’ series) in which either one or both N atoms were free or blocked by an alkyl group. For interpretation of the results, a graph was constructed in which 25 points (actually circles) represent a maximum of 81 aglycone types and 40 arrows indicate 131 possible cyclizations. The reaction matrix of the graph was under thermodynamic control and in most cases afforded the thermodynamically most stable product aglycones. In addition to the deglycosylation, two types of cyclization were observed. In azacyclizations, the preferred nucleophilic site is N-4 over N-1, and the preferred electrophilic site is C-22 in the glycosides, C-21 over C-19 and C-17 in aglycones. In oxacyclizations, the preferred nucleophilic site is O-17 over C-18 and C-21, and the preferred electrophilic site is C-19 over C-21 and C-17 in the ‘natural’ series, C-21 over C-17 in the ‘dihydro’ series. In one case, the kinetically favoured aglycone types which had been generated in the reaction mixture were trapped in a subsequent reaction (outside the graph) before thermodynamic equilibrium was attained. With the help of graphical analysis it was possible to justify the formation of the most favourable and actually isolated products and pathways out of a large number of possibilities.

Some aspects of the chemistry of secologanin

Abstract Secologanin, the representative of more than 650 iridoids and precursor of about 2500 indole, isoquinoline and related alkaloids, is a monoterpenoid glucoside. Its aglucone part is rich in functional groups and stereogenic elements. Our purpose was to study some aspects of its chemistry, and to prepare a bioorganic background for the understanding of its biochemical role. Our work directed mainly toward the reactions of N nucleophiles (including biogenic amines) and the chemical deglucosylation, which opened the way for further chemical transformations. During our work,several new heterocyclic ringsystem were constructed, all the three carbon bonds attached to the single stable chiral center of the molecule could be selectively cleaved, and a new biomimetic aromatization was discovered. NMR technics and graph analysis mainly contributed to the interpretation of the stereochemistry and formation of the reaction products from single educts.

An nmr study of the solution conformation of two asperuloside derivatives

Abstract 3-Methoxy-3,4-dihydro- and the 3-methoxy-3,4,7,8- tetrahydro-asperuloside-tetraacetate were prepared. Total assignment of their 1 H and 13 C NMR spectra was accomplished using 2D shift correlation measurements. The configurations and the conformations of these compounds were determined by the combined analysis of the 3 J coupling constants and NOE factors of the 1 H NMR spectra.

Effect of maternal depression and anxiety on mother’s perception of child and the protective role of social support

ABSTRACT Objective: The purpose of this study was to investigate the impact of postpartum depressive and anxiety symptoms on maternal perception of the infant and the protective role of social support. Background: Adverse effects of perinatal depression on mother–child interaction are well documented; however, the role of maternal perception has not been examined. Methods: We used the data of 431 women enrolled in a prospective study in a single maternity unit. Depressive and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS), the State Trait Anxiety Inventory (STAI), and the mother’s perception of infant with the Mother’s Object Relation Scale (MORS). We used Multidimensional Scale of Perceived Social Support (MSPSS) in order to measure social support. Results: Depressive and anxiety symptoms were positively associated to less positive emotions and a more dominant attitude of child as perceived by mothers. This association was even more significant in the case of trait anxiety. Perceived social support has been found to be a protective factor which was able to reduce this tendency. Conclusion: The findings have potential implications for our understanding of the impact of maternal depressive and anxiety symptoms on the developing mother–infant relationship.

Cerebrovascular Effects of Sustained Norepinephrine Infusion

Publisher Summary This chapter discusses the cerebrovascular effects of sustained norepinephrine infusion. It has been well established that despite cerebral autoregulation, the blood supply of the brain is substantially diminished in hemorrhagic shock. Although the pathogenesis of blood-flow reduction has remained unclear, positive therapeutic results with alpha receptor blockade point to the importance of noradrenergic mechanisms. Because hyperactivity of the sympathetic nervous system during shock produces high local concentrations of norepinephrine around the cerebral vessels, active vasoconstriction could be a significant factor in the development of regional blood flow deficiencies. This possibility is supported by the existence of alpha-adrenergic receptors in the cerebrovascular bed. The chapter presents a few experiments that were performed on immobilized and artificially ventilated rats anesthetized with 50 mg/kg sodium pentobarbital i. p. On the average, mean arterial blood pressure dropped to 68 mmHg, and general acidosis with pH values below 7.0 developed.

NEUROREGULATION OF CEREBRAL BLOOD FLOW

Publisher Summary This chapter discusses the results of a study obtained in situations where either the sympathetic alpha or beta receptors are stimulated or blocked or the parasympathetic influence is abolished by atropine. It also discusses the effect of alpha and beta receptor blockade on the auto regulatory blood flow, blood volume, and NAD/NADH responses. In the study, glass windows holding the stimulating electrodes were implanted into the parietal bone for surface fluororeflectometry in chloralose anesthetized cats. The tissue NADH level as a metabolic parameter was monitored in the cerebral cortex by the in situ fluorometric method. The blood dilution method was used to measure absolute blood flow and blood volume. Local cerebral blood flow was determined in rats by auto-radiography. The animals received 100 microcurie/kg 14C-labeled iodoantipyrine. After freezing the brain, 20 micrometer sliced were cut and the blood flow changes were evaluated in 77 anatomical structures. Phenoxybenzamine treatment itself resulted in a considerable NAD reduction and vascular volume increase. Adrenergic receptors do not have any role in the vasodilataion and vasoconstriction of cerebral vessels during auto regulation. Atropine significantly increases cerebral blood flow in rats. The heterogenous nature of local responses might explain some of the discrepancies found among experimental data.