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