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

Trinadhachari, Ganala Naga; Kamat, A. G.; Babu, K. Raghu; Sanasi, Paul Douglas; Prabahar, Koilpillai Joseph

doi:10.1016/j.tetasy.2013.11.016

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…Simple heating of this last compound with neat ethyl formate provided the formamide 17 in quantitative yield, and this was subjected to a Bischler-Napieralskitype cyclodehydration reaction under conditions defined by Movassaghi and Hill. [24] In order to further corroborate the structural assignments presented above, (Ϯ)-narwedine (18) was subjected to diastereoselective reduction with L-selectride, [24,25] thereby affording (Ϯ)-galanthamine [(Ϯ)-1] in 83 % yield. The spectroscopic data acquired on this tetracyclic compound are in complete accord with those reported by Magnus and co-workers.…”

Section: Resultsmentioning

confidence: 84%

“…[11c] Since racemic narwedine is readily converted into either (+)-or (-)-galanthamine, the present work constitutes a formal total synthesis of both enantiomeric forms of the title alkaloid. [24] In order to further corroborate the structural assignments presented above, (Ϯ)-narwedine (18) was subjected to diastereoselective reduction with L-selectride, [24,25] thereby affording (Ϯ)-galanthamine [(Ϯ)-1] in 83 % yield. The 1 H and 13 C NMR spectroscopic data obtained on this material also proved a good match for those recorded on the natural product.…”

Section: Resultsmentioning

confidence: 84%

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A Total Synthesis of Galanthamine Involving De Novo Construction of the Aromatic C‐Ring

2015

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The tetracyclic alkaloid galanthamine is used clinically in a number of countries for the symptomatic treatment of mild to moderate forms of Alzheimer's disease, and this feature coupled with its novel molecular architecture has prompted an extensive focus on its synthesis. The present study reports a new and distinct synthesis of galanthamine wherein the AB‐ring substructure and associated quaternary carbon centre are constructed by using a palladium‐catalyzed intramolecular Alder‐ene reaction. The product of this process is engaged in a Tsuji–Trost‐type reaction to generate a semicyclic diene that participates in a normal‐electron‐demand Diels–Alder reaction to generate, after oxidation of the initially formed adduct, the aromatic C‐ring of the target alkaloid. Modified Bischler–Napieralski chemistry is then deployed to construct the seven‐membered D‐ring and thereby furnishing narwedine, an established precursor to both (+)‐ and (–)‐galanthamine.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 84%

A Total Synthesis of Galanthamine Involving De Novo Construction of the Aromatic C‐Ring

2015

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“…The mixtures of epimers was subjected to oxidation by using pyridinium chlorochromate giving the desired ent ‐narwedine, spectral and physical properties of which were consistent with those published in the literature . The obtained ent ‐narwedine was reduced stereoselectively with l ‐selectride to give ent ‐galanthamine, spectral and physical properties of which matched those described in the literature .…”

Section: Figurementioning

confidence: 99%

Chemoenzymatic Total Synthesis of (+)‐Galanthamine and (+)‐Narwedine from Phenethyl Acetate

Endoma‐Arias

Hudlický

2016

Chemistry A European J

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The stereoselective total synthesis of unnatural (+)-galanthamine starting from phenethyl acetate is described. Chirality was introduced via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis-cyclohexadi-enediol, configuration of which provided the absolute stereochemistry of the ring C of (+)-galanthamine. Intramolecular Heck cyclization was used to form the quaternary carbon and dibenzofuran functionality. The synthesis of (+)-galanthamine was completed in a total of ten steps and an overall yield of 5.5 %. Experimental and spectral data are provided for all new compounds.

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“…A commercial scale process of galantamine hydrobromide was presented by chemists of Aurobindo Pharma [39,40].…”

Section: Drugs Interacting With Acetyl-and Butyrylcholinesterasementioning

confidence: 99%

“…PBD-150 (Probiodrug, Halle, Sachsen-Anhalt, Germany; Fig. 12) is a potent inhibitor of human glutaminyl cyclase (IC 50 = 17 nM) and totally inhibited formation of A␤ 3,11 -(pE) 40 A potential follow-up compound is PQ-1228 (Structure was not communicated).…”

Section: Drugs Interacting With Glutaminyl Cyclasementioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 2: Drugs Interacting with Enzymes. Update 2014

Froestl

Muhs

Pfeifer

2014

JAD

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Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers are very productive. The review on Drugs interacting with Enzymes was accepted in August 2012. However, this field is very dynamic. New potential targets for the treatment of Alzheimer's disease were identified. This update describes drugs interacting with 60 enzymes versus 43 enzymes in the first paper. Some compounds progressed in their development, while many others were discontinued. The present review covers the evolution of research in this field through April 2014.

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

Cited by 15 publications

References 22 publications

A Total Synthesis of Galanthamine Involving De Novo Construction of the Aromatic C‐Ring

A Total Synthesis of Galanthamine Involving De Novo Construction of the Aromatic C‐Ring

Chemoenzymatic Total Synthesis of (+)‐Galanthamine and (+)‐Narwedine from Phenethyl Acetate

Cognitive Enhancers (Nootropics). Part 2: Drugs Interacting with Enzymes. Update 2014

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