ChemInform Abstract: A General Approach to the Galanthamine Ring System (original) (raw)

Synthesis of galanthamine

Arkivoc, 2001

The synthesis of (±)-and (-)-galanthamine via 3,4-dihydro-6,7-dimethoxy-4'-oxo-spiro[5H]-2-benzazepine-5,1'-[2]cyclohexene]-2(1H)-carboxylic acid ethyl ester (2) is described.

Carbocyclic galanthamine analogs: Incorporating the phenethylamine motif

Journal of Heterocyclic Chemistry, 2002

An unnatural analog of the anti-Alzheimer drug galanthamine bearing a phenethylamine moiety has been prepared as a racemic mixture using K 3 [Fe(CN) 6 ] induced tandem cyclization techniques in the key step to form derivatives of a novel heterocyclic ring system.

Synthesis of β-C-galactosyl d- and l-alanines

Organic & Biomolecular Chemistry, 2012

Synthesis of β-C-D-galactosyl D-and L-alanines is carried out via a highly stereoselective Grignard reaction of glycosyl iodides, Sharpless dihydroxylation and S N 2 displacement of the corresponding mesylate or tosylate. Alternatively, attempted triflation of the intermediate alcohols triggers a stereoselective debenzylative cyclization leading to interesting bicyclic trans-fused compounds. ‡ Electronic supplementary information (ESI) available: 1 H and 13 C NMR spectra for all new compounds and 2D spectra for compounds 9 and 10.

Stereoselective syntheses of galanthamine and its stereoisomers by complementary Luche and L-selectride reductions

Tetrahedron: Asymmetry, 2014

A diastereodivergent approach for the stereoselective syntheses of all four stereoisomers of galanthamine, (À)-galanthamine 1, (+)-galanthamine 2, (À)-epigalanthamine 3, and (+)-epigalanthamine 4, from (±)-narwedine 5 is reported. Thus (±)-narwedine 5 was resolved by dynamic kinetic resolution to obtain enantiomerically pure (À)-narwedine 6 and (+)-narwedine 7. Each enantiomerically pure isomer of narwedine was subjected to Luche and L-selectride reactions to obtain all four isomers of galanthamine. In these reactions, the (À)-galanthamine 1 and (+)-galanthamine 2 isomers were obtained with an enantiomeric purity of >99.5%, whereas (À)-epigalanthamine 3 and (+)-epigalanthamine 4 are obtained with a chiral purity of >97%. The axial hydride attack by the Luche reduction and the equatorial hydride attack by the L-selectride reduction on the cyclic enone system are explored in the stereoselective synthesis of the galanthamine isomers and thus it was demonstrated that the stereoselective synthesis involving the Luche and L-selectride reductions are complementary in yielding enantiomeric stereogenic centers from a prochiral carbonyl group on the cyclic enone system.

Synthesis of (−)- and (+)-8-fluoro-galanthamine

Tetrahedron Letters, 2006

The synthesis of racemic 8-fluorogalanthamine and its separation into (À)-and (+)-8-fluorogalanthamine (= (4aS,6R, 8aS)-and (4aR,6S,8aR)-1-fluoro-4a, 5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol) is described.

Chem. Heterocyclic Compds. 2013, 49, 746-759

We examined the tandem alkylation/[2+4] cycloaddition of 1-(2-furyl)-3,4-dihydroisoquinolines by various allyl halides. It was found that the process occurred through the intermediate formation of 2-allyl-1-furyl-3,4-dihydroisoquinolinium salts with a subsequent intramolecular exo addition of the allyl fragment to the furan ring. The adducts obtained were structural analogs of the isoindolo-[1,2-a]isoquinoline alkaloids jamtine and hirsutine.

Bicyclic glutamic acid derivatives

Chirality, 2006

For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric a-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H 2 SO 4 yielding diastereomeric mixtures of three secondary a-amino a-carbamoyl-gesters and two diastereomeric cis-fused angular a-carbamoyl g-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-a-amino a-carbamoyl-g-esters. Separation was achieved by CC. The pure secondary trans-a-amino a-carbamoyl-g-esters cyclise on heating and treatment with concentrated H 2 SO 4 , respectively, to diastereomeric cis-fused angular secondary a-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary a-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (aR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-aS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide. Chirality 18:383-394, 2006. V V C 2006 Wiley-Liss, Inc.