Knoevenagel-IMHDA and -IMSDA sequences for the synthesis of chiral condensed O,N-, S,N- and N-heterocycles.

Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.

Impact of COVID-19 pandemic on acute stroke care in a tertiary stroke centre.

The aim of this study was to evaluate how COVID-19 affected acute stroke care and outcome in patients with acute ischemic or hemorrhagic stroke. We performed a retrospective analysis on patients who were admitted with acute ischemic (AIS) or hemorrhagic (ICH) stroke from September 2020 to May 2021 with and without COVID-19. We recorded demographic and clinical data, imaging parameters, functional outcome and mortality at one year.