3 research outputs found

    Carbolithiation of <i>S</i>‑Alkenyl‑<i>N</i>‑aryl Thiocarbamates: Carbanion Arylation in a Connective Route to Tertiary Thiols

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    <i>S</i>-Alkenyl-<i>N</i>-arylthiocarbamates are formed from allylic alcohols by sigmatropic rearrangement and isomerization or Cî—»C bond cleavage. They undergo carbolithiation with a range of organolithium reagents, generating benzyllithium intermediates in a stereospecific manner which may undergo N to C aryl migration to yield thiocarbamates with tertiary substituents. A simple base-promoted alcoholysis reveals a series of hindered tertiary thiols with branched carbon skeletons

    Novel Macrocyclic Amidinoureas: Potent Non-Azole Antifungals Active against Wild-Type and Resistant Candida Species

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    Novel macrocyclic amidinourea derivatives <b>11</b>, <b>18</b>, and <b>25</b> were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds <b>11</b> and <b>18</b> were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds <b>25</b> were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole

    Development of Novel Membrane Disrupting Lipoguanidine Compounds Sensitizing Gram-Negative Bacteria to Antibiotics

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    A new class of amphiphilic molecules, the lipoguanidines, designed as hybrids of guanidine and fatty acid compounds, has been synthesized and developed. The new molecules present both a guanidine polar head and a lipophilic tail that allow them to disrupt bacterial membranes and to sensitize Gram-negative bacteria to the action of the narrow-spectrum antibiotics rifampicin and novobiocin. The lipoguanidine 5g sensitizes Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to rifampicin, thereby reducing the antibiotic minimum inhibitory concentrations (MIC) up to 256-fold. Similarly, 5g is able to potentiate novobiocin up to 64-fold, thereby showing a broad spectrum of antibiotic potentiating activity. Toxicity and mechanism studies revealed the potential of 5g to work synergistically with rifampicin through the disruption of bacterial membranes without affecting eukaryotic cells
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