6 research outputs found
Scalable Synthesis of the Amber Odorant 9-<i>epi</i>-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction
A novel biomimetic
nucleophilic bromocyclization reaction is used
in the key step of a new and straightforward synthesis of 9-<i>epi</i>-Ambrox, an organic compound of high interest and value
in the context of fragrances. This strategic reaction allows access
to 9-<i>epi</i>-Ambrox on a gram scale from a dienyne derivative,
easily available from geraniol, following a sequence of seven steps
(35% global yield) with just one purification process. Both enantiomers
of the molecule were obtained by a challenging enzymatic resolution
Synthesis of Cyclohexanones through a Catalytic Cationic Cyclization of Alkynols or Enynes
A novel procedure
for the synthesis of cyclohexanones from alkynol
or enyne derivatives through a cationic cyclization has been developed.
The key points to obtain the six-membered ring derivatives are the
use of starting materials containing a terminal alkyne, the use of
tetrafluoroboric acid as a promoter of the cationic cyclization, and
the appropriate selection of 1,1,1,3,3,3-hexafluoropropan-2-ol
(HFIP) as solvent. This strategy can be extended to the biomimetic
cationic cyclization of several terpene-derived polyenynes
Effect of a Prolonged-Release System of Urea on Nitrogen Losses and Microbial Population Changes in Two Types of Agricultural Soil
The Discovery of Novel Antimalarial Aminoxadiazoles as a Promising Nonendoperoxide Scaffold
Since the appearance
of resistance to the current front-line antimalarial
treatments, ACTs (artemisinin combination therapies), the discovery
of novel chemical entities to treat the disease is recognized as a
major global health priority. From the GSK antimalarial set, we identified
an aminoxadiazole with an antiparasitic profile comparable with artemisinin
(<b>1</b>), with no cross-resistance in a resistant strains
panel and a potential new mode of action. A medicinal chemistry program
allowed delivery of compounds such as <b>19</b> with high solubility
in aqueous media, an acceptable toxicological profile, and oral efficacy.
Further evaluation of the lead compounds showed that in vivo genotoxic
degradants might be generated. The compounds generated during this
medicinal chemistry program and others from the GSK collection were
used to build a pharmacophore model which could be used in the virtual
screening of compound collections and potentially identify new chemotypes
that could deliver the same antiparasitic profile
The Discovery of Novel Antimalarial Aminoxadiazoles as a Promising Nonendoperoxide Scaffold
Since the appearance
of resistance to the current front-line antimalarial
treatments, ACTs (artemisinin combination therapies), the discovery
of novel chemical entities to treat the disease is recognized as a
major global health priority. From the GSK antimalarial set, we identified
an aminoxadiazole with an antiparasitic profile comparable with artemisinin
(<b>1</b>), with no cross-resistance in a resistant strains
panel and a potential new mode of action. A medicinal chemistry program
allowed delivery of compounds such as <b>19</b> with high solubility
in aqueous media, an acceptable toxicological profile, and oral efficacy.
Further evaluation of the lead compounds showed that in vivo genotoxic
degradants might be generated. The compounds generated during this
medicinal chemistry program and others from the GSK collection were
used to build a pharmacophore model which could be used in the virtual
screening of compound collections and potentially identify new chemotypes
that could deliver the same antiparasitic profile
Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial
Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. Results: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors