piperidines and streptazolin

The synthesis of optically active substituted piperidines has been achieved by using four different methodologies. The first one is an intramolecular nucleophilic displacement of activated alcohol moieties that was used to build up the piperidine ring of (-)-prosophylline and (-)-slaframine, and the second one is a ring-closing metathesis of unsaturated amines which was employed in the synthesis of (+)-sedamine and 4a,5-dihydrostreptazoline. The third methodology is the alpha-functionalization of N-Boc piperidines which was particularly useful in the synthesis of argatroban, and the fourth one is a ring expansion of prolinols to 3-chloropiperidines or 3-hydroxypiperidines which was utilized to synthesize (-)-paroxetine, (-)-pseudoconhydrine, the piperidine ring of (-)-velbanamine and (+)-zamifenacin.

Topics: Alkaloids; Arginine; Chemistry; Dioxoles; Paroxetine; Pipecolic Acids; Piperidines; Pyrrolidines; Sulfonamides

Streptomyces thermoviolaceus SRC3, a newly isolated actinobacterial strain from Algerian river sediments, exhibited a broad activity against various bacterial and yeast human pathogens (Salmonella Typhi ATCC 14028, Vibrio cholerae ATCC 14035, MRSA ATCC 43300 and Candida albicans ATCC 10231). The strain SRC3 was selected from thirty nine actinobacterial isolates and identified as S. thermoviolaceus based on morphology, cultural properties, physiological analyses and 16S rRNA gene sequencing. Culture parameters for the antibiotic production were optimized by sequential statistical strategy including Plackett-Burman design (PBD) and Response Surface Methodology (RSM). In PBD experiments, KCl, K

Topics: Algeria; Anti-Infective Agents; Bacteriological Techniques; Candida albicans; Culture Media; DNA, Bacterial; DNA, Ribosomal; Geologic Sediments; Methicillin-Resistant Staphylococcus aureus; Piperidines; Rivers; RNA, Ribosomal, 16S; Salmonella typhi; Sequence Analysis, DNA; Streptomyces; Time Factors; Vibrio cholerae

Two new alkaloids, strepchazolins A (

Topics: Acetylcholinesterase; Alkaloids; Anti-Bacterial Agents; Bacillus subtilis; China; Cholinesterase Inhibitors; Crystallography, X-Ray; Inhibitory Concentration 50; Marine Biology; Microbial Sensitivity Tests; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Piperidines; Stereoisomerism; Streptomyces

Rising rates of antibiotic resistance in bacterial pathogens is a medical crisis of global concern that necessitates the development of new treatment strategies. We have isolated a natural product with macrophage-stimulating activity from a screen of microbially produced bioactive molecules. Streptazolin increased bacterial killing and elaboration of immunostimulatory cytokines by macrophages in vitro. Furthermore, we show that streptazolin stimulates the macrophage nuclear factor κB (NF-κB) pathway via phosphatidylinositide 3-kinase (PI3K) signaling, and that the conjugated diene moiety is essential for stimulatory activity. Immunostimulatory molecules like streptazolin represent entries into new treatment paradigms to address the challenge of antibiotic resistance.

Topics: Anti-Bacterial Agents; Biological Products; Cell Line; Cytokines; Drug Discovery; Drug Resistance, Bacterial; Humans; Macrophages; NF-kappa B; Phosphatidylinositol 3-Kinase; Piperidines; Signal Transduction

Two new compounds, isostreptazolin (1) and sannaphenol (2), were isolated from the culture broth of Streptomyces sannanensis and their structures elucidated on the basis of 1D and 2D NMR as well as MS, IR and UV spectroscopic data analysis. The cytotoxic activity of 1 and 2 were evaluated. Both compounds were inactive against H460 and HeLa cell lines at 100 mM.

Topics: Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Magnetic Resonance Spectroscopy; Phenols; Piperidines; Streptomyces

A stereoselective total synthesis of (+)-streptazolin 1 was accomplished starting from readily available aminocyclopentenol (-)-7. The synthetic sequence highlights an intramolecular aldol condensation strategy to construct the piperidine core and a silicon-tethered ring-closing metathesis strategy to install the Z exocyclic ethylidene side chain of streptazolin. Separate protodesilylation and Tamao oxidation of a common intermediate 32 afforded streptazolin and the precursor for 13-hydroxystreptazolin. The overall yield for (+)-streptazolin 1 from aminocyclopentenol (-)-7 was 4.8% for a total of 16 steps.

Topics: Cyclization; Cyclopentanes; Molecular Conformation; Oxidation-Reduction; Piperidines; Silicon; Stereoisomerism

The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable heptynyl appendage gave exclusively the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-ene-7,10-diones. On the basis of this newly developed Pauson-Khand reaction of 2-oxazolone-alkyne derivatives, the first total synthesis of (+/-)-8alpha-hydroxystreptazolone was accomplished in a highly stereoselective manner. In addition, (+/-)-7-epi-8alpha-hydroxystreptazolone was also synthesized.

Topics: Alkynes; Anti-Infective Agents; Biological Products; Heterocyclic Compounds, 3-Ring; Ketones; Oxazoles; Piperidines; Stereoisomerism

Topics: Alkynes; Catalysis; Cyclization; Palladium; Piperidines; Stereoisomerism; Streptomyces

Concise total syntheses of (+)-streptazolin 1 and its more stable dihydro derivative 2 were accomplished via an intramolecular aldol condensation strategy starting from readily available aminocyclopentenol (-)-7. The synthetic sequence included reductive amination, stereoselective epoxidation, intramolecular aldol (and condensation) reaction, and Wittig reaction. The overall yield for dihydro derivative 2 from aminocyclopentenol (-)-7 was about 7% for a total of 14 steps.

Topics: Acylation; Cyclopentanes; Molecular Conformation; Nitroso Compounds; Piperidines; Stereoisomerism

Variation of the culture conditions of Streptomyces sp. strain A1, which produces streptazolin (1), resulted in the isolation of four new co-metabolites: 5-O-(beta-D-xylopyranosyl)streptazolin (3), 9-hydroxystreptazolin (4), 13-hydroxystreptazolin (5), and streptenol E (6). Their structures were established by spectroscopic and chemical methods. The possible biosynthetic relationship between the streptazolins and the streptenols is discussed.

Topics: Antibiotics, Antineoplastic; Culture Media; Drug Screening Assays, Antitumor; Fermentation; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Piperidines; Streptomyces; Tumor Cells, Cultured