Oxidative photochemical decarboxylation of zaragozic acid A

A unique decomposition reaction of the novel squalene synthase inhibitors called zaragozic acids has been studied. Under very mild conditions, e.g. by merely exposing their solutions to air and visible light at ambient temperature, these compounds, characterized by the 2,8-dioxabicyclo[3.2.1]octane-4,6,7-trihydroxy-3,4,5-tricarboxylic acid core, rapidly decompose. As relatively stable intermediates in the cascade of decomposition, the biologically active 2,8-dioxabicyclo[3.2.1]octane-6,7-dihydroxy-4-keto-5-caroxylic acid (or 3,4-decarboxy-4-dehydro) derivatives of these compounds have been isolated in ca. 20% yield. Derivatization on the highly reactive 4-carbonyl group yields stable derivatives, several of which are potent inhibitors of squalene synthase. Further decomposition results in the elimination of C3 and C4 atoms and the carboxylic acid on C5, the oxidation of C5 to carboxylic acid and the liberation of the oxo group on C1. Specific results obtained with zaragozic acid A, a key representative of the family of these potent cholesterol-lowering agents, are presented in this study.     

New utilizations of the phenacyloxy protecting group in peptide synthesis

Zusammenfassung Es wird über weitere Verwendungsmöglichkeiten der Phenacyloxy-Gruppe in der Peptidsynthese berichtet. Phenacyloxyester reagieren leicht mit Hydrogencyanid unter Bildung der entsprechenden 2-Cyano-2-phenyl-vinyl-ester, welch letztere Derivate sich als gute Acylierungsmittel erwiesen.

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Acknowledgement. I thank ProfessorM. Bodanszky for valuable discussions and advice. Financial support for the research has been provided by the National Science Foundation.     

Direct aromatization of C19-steroid sulphates

Zusammenfassung Bei Bebrütung von synthetischem 7-³H-Androst-4-en-3, 17-dion-³⁵S-sulfat mit Mikrosomen aus menschlicher Placenta in Gegenwart von NADPH₂ wurden 15.9% des Substrats in doppelt-markiertes Östron-sulfat mit unverändertem³H/³⁵S-Verhältnis umgewandelt. Da die Ausbeute vergleichsweise höher lag als bei Verwendung von 7-³H-Dehydroepiandrosteron-³⁵S-sulfat, wird angenommen, dass die Biosynthese von Östron-sulfat aus Dehydroepiandrosteron-sulfat über ein dem Androst-4-en-dion entsprechendes 3,5-Dienol-sulfat verläuft.

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This investigation was carried out with the support of the Deutschen Forschungsgemeinschaft, Bad Godesberg.     

In vivo perfusion of the human ovary with 4-14C-dehydroepiandrosterone and 7α-3H-dehydroepiandrosterone35S-sulfate. Biosynthesis of steroid hormones in human gonads,V

Zusammenfassung Nach in-vivo-Perfusion eines menschlichen Ovars mit 4-¹⁴C-DHEA und 7-³H-DHEA-³⁵S-sulfat lagen rund 15% der freien C₁₉- und C₁₈-steroide im Ovarialvenenblut als³H- und 85% als¹⁴C-markierte Verbindungen vor. Die Fraktion der sulfokonjugierten Steroide, bestehend aus 60% Steroidsulfatiden und 40% Steroidsulfaten, enthielt etwa 69% doppeltmarkierte, 27%³H- und 4%¹⁴C-markierte Sulfokonjugate. Neben dem vorzugsweise direkten Metabolismus des sulfokonjugierten DHEA liess sich auch ein indirekter Stoffwechsel zu Androgenen und Östrogenen nachweisen.

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This investigation was supported by the Deutsche Forschungsgemeinschaft, 532 Bad Godesberg (Germany)     

Clusters of iron-rich cells in the upper beak of pigeons are macrophages not magnetosensitive neurons

Understanding the molecular and cellular mechanisms that mediate magnetosensation in vertebrates is a formidable scientific problem. One hypothesis is that magnetic information is transduced into neuronal impulses by using a magnetite-based magnetoreceptor. Previous studies claim to have identified a magnetic sense system in the pigeon, common to avian species, which consists of magnetite-containing trigeminal afferents located at six specific loci in the rostral subepidermis of the beak. These studies have been widely accepted in the field and heavily relied upon by both behavioural biologists and physicists. Here we show that clusters of iron-rich cells in the rostro-medial upper beak of the pigeon Columbia livia are macrophages, not magnetosensitive neurons. Our systematic characterization of the pigeon upper beak identified iron-rich cells in the stratum laxum of the subepidermis, the basal region of the respiratory epithelium and the apex of feather follicles. Using a three-dimensional blueprint of the pigeon beak created by magnetic resonance imaging and computed tomography, we mapped the location of iron-rich cells, revealing unexpected variation in their distribution and number--an observation that is inconsistent with a role in magnetic sensation. Ultrastructure analysis of these cells, which are not unique to the beak, showed that their subcellular architecture includes ferritin-like granules, siderosomes, haemosiderin and filopodia, characteristics of iron-rich macrophages. Our conclusion that these cells are macrophages and not magnetosensitive neurons is supported by immunohistological studies showing co-localization with the antigen-presenting molecule major histocompatibility complex class II. Our work necessitates a renewed search for the true magnetite-dependent magnetoreceptor in birds.     

Excretion of C19-Steroids in human seminal fluid

Zusammenfassung Sechs Stunden nach i.v. Verabreichung von 7-³H-Dehydroepiandrosteron-³⁵S-sulfat enthielt das Sperma eines 43jährigen Mannes 0.033% injizierter³H-Aktivität. Hiervon entfielen 0.010% auf freie Steroide, 0.021% auf Sulfokonjugate und 0.002% auf Steroid-glucuronoside. Die aus Steroid-sulfatiden und-sulfaten bestehenden Sulfokonjugate wiesen ein nur geringfügig verschobenes Isotopenverhältnis³H/³⁵S auf (3.78 und 3.40 gegenüber 2.88). In den verschiedenen Fraktionen konnten ausser Dehydroepiandrosteron auch Androsteron, Androstendion und weitere C₁₉-Steroide nachgewiesen werden.