-Secretase-1: In Silico Drug Reposition for Alzheimer's Disease.

The -secretase-1 enzyme (BACE-1) performs a key role in the production of beta-Amyloid protein (Aβ), which is associated with the development of Alzheimer's disease (AD). The inhibition of BACE-1 has been an important pharmacological strategy in the treatment of this neurodegenerative disease. This study aims to identify new potential candidates for the treatment of Alzheimer's with the help of in silico studies, such as molecular docking and ADME prediction, from a broad list of candidates provided by the DrugBank database.

Chiral Indolizinium Salts Derived from 2-Pyridinecarbaldehyde-First Diastereoselective Syntheses of (-)-1-lentiginosine.

The first diastereoselective synthesis of (-)-1--lentiginosine from a common chiral -epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-- cyclization of tosylate -epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

Diastereoselective synthesis of new zwitterionic bicyclic lactams, scaffolds for construction of 2-substituted-4-hydroxy piperidine and its pipecolic acid derivatives.

The synthesis of new chiral highly functionalized zwitterionic bicyclic lactams starting from acyclic β-enaminoesters derived from ()-(-)-2-phenylglycinol is described. The key step involved an intramolecular non-classical Corey-Chaykovsky ring-closing reaction of the corresponding sulfonium salts derived from β-enaminoesters. This methodology permits the generation of two or three new stereogenic centers with high diastereoselectivity.

Curcumin induces cortico-hippocampal neuronal reshaping and memory improvements in aged mice.

Aging induces cognitive decline, reduces of synaptic plasticity and increases oxidative reactive species (ROS) in the central nervous system. Traditional medicine has long benefitted from naturally occurring molecules such as curcumin (diferuloymethane). Curcumin is extracted from the plant Curcuma longa and is known for its synaptic and antioxidant-related benefits.

Retro-Curcuminoids as Mimics of Dehydrozingerone and Curcumin: Synthesis, NMR, X-ray, and Cytotoxic Activity.

Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named -curcuminoids (-), was synthesized and characterized using 1D ¹H- and C-NMR, IR, and mass spectrometry; the X-ray structure of , , , , , , and are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α, β-unsaturated ketone functionality.

Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats.

Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment.

The influence of sulfur configuration in H NMR chemical shifts of diasteromeric five-membered cyclic sulfites.

The effect of the stereochemistry of the sulfur atom on H chemical shifts of the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5-phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete H and C NMR spectral assignment was achieved by the use of one-dimensional and two-dimensional NMR techniques in combination with X-ray data. A correlation of experimental data with theoretical calculations of chemical shift tensors using density functional theory and topological theory of atoms in molecules was made.

Crystal structures of two chiral piperidine derivatives: 1-[(1R)-2-hy-droxy-1-phenyl-eth-yl]piperidin-4-one and 8-[(1S)-1-phenyl-eth-yl]-1,4-dioxa-8-aza-spiro-[4.5]decane-7-thione.

The crystal structures of the two title piperidine derivatives show different conformations for the six-membered heterocycle. The N-substituted 4-piperidinone 1-[(1R)-2-hy-droxy-1-phenyl-eth-yl]piperidin-4-one, C13H17NO2, (I), has a chair conformation, while the piperidine substituted in position 2 with a thio-carbonyl group, 8-[(1S)-1-phenyl-eth-yl]-1,4-dioxa-8-aza-spiro-[4.5]decane-7-thione, C15H19NO2S, (II), features a half-chair conformation.

4-Hy-droxy-1,1'-bis-[(S)-1-phenyl-eth-yl]-5,5',6,6'-tetra-hydro-3,4'-bipyridine-2,2'(1H,1'H)-dione.

The title bis-piperidine, C26H28N2O3, was unexpectedly obtained via a dimerization mechanism promoted by acetic acid when performing the Dieckmann cyclization of a chiral amido ester. The S,S configuration was assigned by reference to the enanti-omerically pure starting material. In the mol-ecule, two core heterocycles are linked by a σ bond.

(1) H and (13) C NMR characterization of new cycloartane triterpenes from Mangifera indica.

From the stem bark of Mangifera indica, seven cycloartane-type secondary metabolites were isolated. Compound 1 has been isolated for the first time from M. indica, whereas compounds 2 (2a and 2b, as an epimeric mixture), 3, and 4 are new triterpenoid-type cycloartanes.

(1'S,2R,3R)-(-)-2-Hydr-oxy-3-morpholino-3-phenyl-N-(1'-phenyl-ethyl)propion-amide.

In the title compound, C(21)H(26)N(2)O(3), the morpholine ring has a chair conformation and the dihedral angle between the two phenyl rings is 59.0 (3)°. The crystal packing is stabilized by inter-molecular O-H⋯O hydrogen bonds, generating a ribbon structure along the a axis.

Isolation and characterization of five new tetrasaccharide glycosides from the roots of Ipomoea stans and their cytotoxic activity.

Five new tetrasaccharide glycosides, stansins 1-5, were isolated from the roots of Ipomoea stans, and their structures were elucidated using spectroscopic and chemical methods. Preliminary testing showed the cytotoxicity of 5 toward the OVCAR and UISO-SQC-1 cancer cell lines.

An enantioselective access to 1-alkyl-1,2,3,4-tetrahydroisoquinolines. Application to a new synthesis of (-)-argemonine.

Potassium ferricyanide oxidation of salt 1 gave isoquinolinone 7 whose treatment with Grignard reagents resulted in a high-yield formation of substituted isoquinolinium salts 5. The selectivity of the reduction of these salts to give derivatives 6 has been studied. Particularly good selectivities (82-84%) were observed when R is a benzylic group.

Crystal structure of trans(3R,2aS)-(-)-3-phenyl-hexahydro-oxazolo[3,2-a]pyridin-5-one.

Chiral, non-racemic hexahydro-oxazolo[3,2-a]pyridin-5-ones are strategic starting materials for the asymmetric synthesis of alkaloids, via the stereoselective C-C bond formation at the position a to the nitrogen atom. The stereoselectivity of this key step is mainly driven by the geometry of the fused rings of the oxazolopyridine moiety. In this work, the synthesis and X-ray structure of trans(3R,2aS)-(-)-3-phenyl-hexahydro-oxazolo[3,2-a]pyridin-5-one is reported.

(-)-(1'S,4aS,7R,8aR)-4a-ethyl-7-hydroxy-1-(1'-phenylethyl)perhydroquinolinium bromide.

In the structure of the title compound, C(19)H(30)NO(+).Br(-), the rings of the perhydroquinolinium moiety are cis fused. The successful reduction of the ketone functionality of the quinolinone used as starting material is confirmed by the hydroxy C-O bond length of 1.