Concise asymmetric synthesis of (5R)-6-hydroxy-3,8-dioxabicyclo[3.2.1]octane derivatives

[reaction: see text] A concise method to asymmetrically synthesize 6-hydroxy-3,8-dioxabicyclo[3.2.1]octane (HDBO) derivatives was devised.     

Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands

In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.     

Synthesis of (−)-(4R,5R)- and (+)-(4S,5S)-1-alkyl-4-(4′-nitrophenyl)-1-azonium-3,7-dioxabicyclo[3.3.0]octane halides

A preparative method has been proposed for the synthesis of bicyclic quaternary ammonium salts via sequential treatment of (–)-(1R,2R)- and (+)-(1S,2S)-1-(4-nitrophenyl)-2-amino-1,3-propanediol with paraform followed by an alkyl halide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1394–1395, October, 1990.     

Enantioselective synthesis and selective monofunctionalization of (4R,6R)-4,6- dihydroxy-2,8-dioxabicyclo[3.3.0]octane

An efficient, enantioselective synthesis of a disubstituted bis-THF scaffold 5 is described, as well as an efficient differentiation of the 1,3-diol unit. [reaction: see text]     

Stereospecificity of the reaction of (+)-(4S, 5S)-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3.3.0]octane with methyl iodide

The MINDO3, MNDO, AM1, and PM3 methods have been used to optimize the geometries of (+)-(4S,5S)-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3.3.0]octane and (+)-(4S,5S)-4-phenyl-1-aza-3,7-dioxabicyclo-[3.3.0]octane. It has been shown that the stereospecificity, of the reaction of the former with methyl iodide is due to the high stability of one of the possible conformers. Pharmacy Faculty 28, University of the Auvergne, Henri Dunant Place, Clermont-Ferrand, France; Samara State University, Samara 443011, Russia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1424–1427, October, 1999.     

Reaction of 8,8-diethyl-6-imino-3-(pentan-3-yl)-2,7-dioxabicyclo[3.2.1]octane-4,4,5-tricarbonitrile with Ketoximes

Russian Journal of Organic Chemistry -     

X-ray structural analysis of (1R,2R,4S,5S,8S)-2,8-bis(4-chlorophenyl)-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3,3,0]octane

The configuration of the asymmetric atoms in the molecule of (1R,2R,4S,5S,8S)-2,8-bis(4-chlorophenyl)-4-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3,3,0]octane has been determined using X-ray analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 930-934, June, 2006.     

Synthesis of 1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-Mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose

1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose were synthesized.     

Identification,synthesis and conformational study of a CN(R,S) synthon by-product: (5R, 10R)-5,10-diphenyl-1,6-diaza-3,8-dioxabicyclo[4.4.1]undecane

The title compound, containing a new heterocyclic skeleton, was identified by X-ray crystallography as the product of condensation of (R)-phenylglycinol with an excess of formaldehyde. The molecule adopts a rigid double twist-chair conformation in both solid and solution states.     

Stereo- and enantioselective synthesis of (−)-(1R,3R,5S)-1,3-dimethyl-2,9-dioxabicyclo [3.3.1] nonane

The title compound has been synthtised in an enantioselective and diastereoselective manner from an optically pure lactol obtained via an enzymatic hydrolysis.     

Crystal Structure of (3S, 6S, 7R, 8R)-3,6-Bis-diphenylphosphino-1,4-dioxabicyclo〔3.3.0〕octane

1INTRoDUCTIONThetitlecompoundhasbeenfoundtobeaveryefficientchiralligandusedtoco-ordinatewithpalladiumformingcatalystsystemsforasymmetrichydroesterificationofnorborneneandstyrene.Intheseasymmetriccatalyticreactions,thechiralinduc-tionofthetitlecompoundisratherstronggivingveryhighoptica1yields(>9o%)ofproductstl3.Inordertostudytherelationshipoftheperformanceandthestructureofthisligand,itisimportanttodeterminethemolecularstructureofthechiraldiphos-phinecompound,whichwaspreparedbytheliteraturem…     

Asymmetric Synthesis of （-）-（4R, 5R）-4-[5-（Benzo[1, 3]dioxol-5-yl）-4- hydroxyl- 1-（pyridin-2-yl）-4, 5-dihydro- 1H-pyrazol-3-yl]benzamide

For discovering novel small molecule inhibitors of transforming growth factor-β1(TGF-β1)type-I receptor(ALK5),we designed1,3,5-triaryl-4-hydroxyl-4,5-dihydro-1H-pyrazole(1)as target compound,mimic the structure of SB-431542which is a2-pyridyl substituted triarylimiazole inhibitor of ALK51.Racemic compound1showed moderate ALK5inhibitory activity in luciferase reporter assays[inhibition(%control):0.1umol/L8.79%;1umol/L19.05%].To investigate the influence of the absolute configuration of…