- Synthesis of (-)-Cytisine Using a 6- endo aza-Michael Addition
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An asymmetric synthesis of (-)-cytisine has been achieved. The piperidine C-ring was formed using a stereodivergent intramolecular 6-endo aza-Michael addition. The B-ring was established by intramolecular pyridine N-alkylation. The absolute stereochemistry was established by an Evans acyl oxazolidinone enolate alkylation reaction that proceeded with an unexpected stereochemical outcome due to participation of the pyridine nitrogen lone pair.
- Barát, Viktor,Csókás, Dániel,Bates, Roderick W.
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p. 9088 - 9095
(2018/07/25)
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- The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular “Inside-Out” Approach
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Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an α,N-fused 2-pyridone, an endo- or exo-α,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular “inside-out” approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C2-symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the α,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es.
- Scharnagel, Dagmar,Goller, Jessica,Deibl, Nicklas,Milius, Wolfgang,Breuning, Matthias
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supporting information
p. 2432 - 2435
(2018/02/16)
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- Concise synthesis of (±)-cytisine via lithiation of N-Boc-bispidine
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(Chemical Equation Presented) (±)-Cytisine has been synthesized in 19% overall yield via a six-step approach from commercially available materials. Key features of this new strategy are as follows: (i) initial construction of the bispidine core, (ii) lithiation-transmetalation-allylation of an N-Boc-bispidine, and (iii) a Pd/C-mediated dihydropyridone oxidation-N- debenzylation process.
- Stead, Darren,O'Brien, Peter,Sanderson, Adam J.
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p. 4459 - 4462
(2007/10/03)
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- Total Enantioselective Synthesis of (-)-Cytisine
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(Equation presented) The first total enantiosynthesis of the biologically active alkaloid (-)-cytisine is reported, featuring a ruthenium-catalyzed RCM reaction as the key step. The approach relies on readily available cis-piperidine-3,5-dimethanol monoacetate as the chiral building block, and it is suited for achieving the target compound in both enantiomeric forms.
- Danieli, Bruno,Lesma, Giordano,Passarella, Daniele,Sacchetti, Alessandro,Silvani, Alessandra,Virdis, Andrea
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p. 493 - 496
(2007/10/03)
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- Total synthesis of (±)-cytisine
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(equation presented) The nicotine partial agonist cytisine was prepared in five steps featuring an "in situ" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]-nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.
- O'Neill, Brian T.,Yohannes, Daniel,Bundesmann, Mark W.,Arnold, Eric P.
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p. 4201 - 4204
(2007/10/03)
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- Total synthesis of (+/-)-cytisine via the intramolecular heck cyclization of activated N-alkyl glutarimides.
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[reaction:see text] A synthesis of racemic cytisine 1 has been developed utilizing an intramolecular Heck cyclization to prepare the bridged tricyclic intermediate 2. The cyclization employs activated glutarimide-derived ketene aminals 3 (X = P(O)OEt(2) or SO(2)CF(3)) and represents the first use of such intermediates in metal-catalyzed processes.
- Coe
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p. 4205 - 4208
(2007/10/03)
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