2,3-Anti selective aldol reaction of phenylacetonitrile

Diastereoselective (3.3:1 to >50:1) aldol reaction of nitriles and aldehydes is reported for the first time; concentration studies and the observed 2,3-anti selectivity suggest the intermediacy of a monomeric N-lithiated nitrile anion. © 1994 American Chemical Society

Memory of chirality: An emerging strategy for asymmetric synthesis

'Memory of chirality' (MOC) is an intriguing strategy for asymmetric synthesis because it appears to do the impossible: the sole chiral center of a molecule directs the stereochemical course of a reaction even though that center is destroyed in the key reactive intermediate. This review describes the critical role of transient conformational chirality in these processes, and defines the three essential requirements for success in an MOC method. The growing application of MOC to asymmetric synthesis methodology is discussed, with extensive coverage of enolate, radical, photochemical and carbocation reactions

Development and applicaption of the nitrile aldol reaction

The role of electronice effects in determining aldol diastereoselection is investigated, by electronic perturbation of both the aldehyde and arylacetonitrile components. Secondly, a preliminary investigation of the aldol stereoselectivity of aliphatic nitriles is described. Finally we demonstrate the transformation of β-hydroxy nitriles to a variety of diastereomerically pure and highly functionalized acyclic and heterocyclic γ - amino alcohol derivatives

Neuroprotection against excitotoxic and ischemic insults by bis(12)-hupyridone, a novel anti-acetylcholinesterase dimer, possibly via acting on multiple targets

The activation of N-methyl-d-aspartate (NMDA) receptors by excessive release of glutamate is involved in the pathogenesis of ischemic stroke. Thus the NMDA receptor has become an attractive therapeutic target for the development of neuroprotectants, especially from antagonists with moderate to low affinity. In the current study, NMDA receptor blockage and neuroprotective effects of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor derived from a naturally occurring monomeric analog huperzine A, were investigated in vitro and in vivo. In primary rat cerebellar granule neurons, B12H (0.1 nM to 1 μM) prevented glutamate-induced apoptosis in a concentration- and time-dependent manner. Receptor-ligand binding analysis showed that B12H competed with [3H]MK801 with a Ki value of 7.7 μM. In the 2-hour middle cerebral artery occlusion rat model, B12H (0.4 and 0.8 mg/kg, 30 min before-ischemia and 15 min post-ischemia, i.p.) significantly attenuated ischemia-induced apoptosis in the penumbra region, improved neurological behavior impairment, and decreased cerebral infarct volume, cerebral edema and neuronal apoptosis in the stroke model. Together, these results showed that B12H moderately blocks NMDA receptors at MK801 site and exerts neuroprotection against excitotoxic and ischemic insults in vitro and in vivo. Combined with our previous publications, we conjecture that B12H might exert neuroprotection via acting on multiple targets. © 2011 Elsevier B.V. All rights reserved