α-Hydroxy ketones as masked ester donors in Brønsted base catalyzed conjugate additions to nitroalkenes
Fecha
2018Autor
Versión
Acceso abierto / Sarbide irekia
Tipo
Artículo / Artikulua
Versión
Versión aceptada / Onetsi den bertsioa
Identificador del proyecto
MINECO//CTQ2016-78487-C2
Impacto
|
10.1002/chem.201705968
Resumen
The catalyst-controlled enantioselective direct addition reaction of enolizable esters and related carboxylic
acid derivatives to p electrophiles remains a difficult synthetic transformation. In this study, the suitability of a-hydroxy
ketones as ester equivalents capable of being activated by
bifunctional Brønsted base catalysts in the context of conjugate addition reactions to nitroolefins i ...
[++]
The catalyst-controlled enantioselective direct addition reaction of enolizable esters and related carboxylic
acid derivatives to p electrophiles remains a difficult synthetic transformation. In this study, the suitability of a-hydroxy
ketones as ester equivalents capable of being activated by
bifunctional Brønsted base catalysts in the context of conjugate addition reactions to nitroolefins is demonstrated. The
scope of the reaction, which affords the corresponding Michael adducts with very high stereoselectivity (diastereomeric ratio (d.r.) +95:5, up to 99% enantiomeric excess (ee)),
and its limitations are explored, as is the aftermath elaboration of adducts into densely functionalized enantioenriched
products. [--]
There is now growing evidence that parkinsonism and
other extrapyramidal signs are highly prevalent in
patients with first-episode psychosis who have never been
exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population
remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis
were enrolled on ...
[++]
There is now growing evidence that parkinsonism and
other extrapyramidal signs are highly prevalent in
patients with first-episode psychosis who have never been
exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population
remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis
were enrolled on the study and followed up for 6 months.
Seventy-seven completed assessments at 3 time points
(baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor
abnormalities. The Simpson-Angus Scale (SAS) was
used for the assessment of extrapyramidal signs, and
each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore
the longitudinal relationships between parkinsonism
scores and cognitive impairment. Parkinsonism scores
showed significant strong longitudinal associations with
deficits in memory, executive functioning, and attention.
Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high
6-month predictive values for cognitive impairment. In
addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia,
akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor
subscores on the SAS scale. These results emphasize the
relevance of the assessment of parkinsonism signs prior
to starting to administer antipsychotic drugs, as core
manifestations of psychotic illness with a high predictive
value for cognitive impairment. [--]
Materias
Addition,
Asymmetric catalysis,
Esters,
Organocatalysis,
Synthesis design
Editor
Wiley
Publicado en
Chemistry - A European Journal 2018, 24, 3893 – 3901
Departamento
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. Institute for Advanced Materials and Mathematics - INAMAT2 /
Universidad Pública de Navarra. Departamento de Química Aplicada /
Nafarroako Unibertsitate Publikoa. Kimika Aplikatua Saila
Versión del editor
Entidades Financiadoras
Support has been provided by the University of the Basque Country UPV/EHU (UFI QOSYC 11/22); the Basque Government (GV grant No IT-628-13); and the Ministerio de Economía y Competitividad (MEC Grant CTQ2016-78487-C2), Spain. I.O. thanks UPV/EHU for a fellowship, and T.C. thanks MEC for a FPI Grant.