- A Concise Asymmetric Total Synthesis of (+)-Epilupinine
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Asymmetric total synthesis of (+)-epilupinine was achieved in just three steps using only commercially available common reagents. The total synthesis involved alkylations of N-nosylamide, ozone oxidation, and sequential reactions of the removal of the nosyl group, intramolecular dehydrative condensation, intramolecular Mannich reaction catalyzed by l-proline, and a reduction.
- Tsutsumi, Tomohiro,Karanjit, Sangita,Nakayama, Atsushi,Namba, Kosuke
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p. 2620 - 2624
(2019/04/30)
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- Pyrrolizidines, indolizidines and quinolizidines via a double reductive cyclisation protocol: concise asymmetric syntheses of (+)-trachelanthamidine, (+)-tashiromine and (+)-epilupinine
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The asymmetric syntheses of pyrrolizidine, indolizidine and quinolizidine alkaloids have been achieved using the diastereoselective conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to α-alkenyl-α,β-unsaturated esters followed by diastereoselective protonation of the resultant enolates as the key stereodefining steps. The azabicyclic scaffolds were then efficiently constructed upon sequential oxidative cleavage of the olefinic units within the resultant β-amino esters and hydrogenolytic N-debenzylation of the corresponding dialdehydes, which occurs with concomitant double reductive cyclisation. Subsequent reduction of the ester moieties with LiAlH4gave (+)-trachelanthamidine, (+)-tashiromine, (1S,8aR)-1-(hydroxymethyl)octahydroindolizine and (+)-epilupinine in 4.9, 4.1, 3.0 and 5.9% overall yield, respectively, in only six steps from commercially available starting materials.
- Brambilla, Marta,Davies, Stephen G.,Fletcher, Ai M.,Roberts, Paul M.,Thomson, James E.,Zimmer, David
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p. 7417 - 7429
(2016/11/11)
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- Enantioselective Aza-Sakurai Cyclizations: Dual Role of Thiourea as H-Bond Donor and Lewis Base
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An enantioselective, catalytic aza-Sakurai cyclization of chlorolactams has been developed as an efficient entry into indolizidine and quinolizidine frameworks. Structure-enantioselectivity relationship studies and mechanistic analysis point to a dual role of the catalyst wherein the thiourea moiety of the catalyst is engaged in both anion binding and Lewis base activation of a substrate.
- Park, Yongho,Schindler, Corinna S.,Jacobsen, Eric N.
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supporting information
p. 14848 - 14851
(2016/11/29)
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- Organocatalytic asymmetric mannich cyclization of hydroxylactams with acetals: Total syntheses of ( )-epilupinine, ( )-tashiromine, and ( )-trachelanthamidine
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An asymmetric, organocatalytic, one-pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89% yield and 97% ee. The total syntheses of (-)-epilupinine, (-)-tashiromine, and (-)-trachelanthamidine also achieved to demonstrate the generality of the process.
- Koley, Dipankar,Krishna, Yarkali,Srinivas, Kyatham,Khan, Afsar Ali,Kant, Ruchir
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supporting information
p. 13196 - 13200
(2015/02/19)
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- Total synthesis of (+)-epilupinine via an intramolecular nitrile oxide-alkene cycloaddition
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Total synthesis of (+)-epilupinine was accomplished in nine steps and in 48% overall yield, in which INOC was used as the key step for the construction of the quinolizidine skeleton. We found that it was an extremely difficult task to prepare the key intermediates (R)-N-(3-nitropropyl)-2-vinylpiperidine or (R)-(2-vinylpiperid-1-yl)propanal by routine methods. Thus, by using Fukuyama's oxime synthesis, a general method was developed for highly efficient conversion of 3-(N,N-dialkylamino)propanols into 3-(N,N-dialkylamino)propanal oximes without using the corresponding aldehydes.
- Su, Deyong,Wang, Xinyan,Shao, Changwei,Xu, Jimin,Zhu, Rui,Hu, Yuefei
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supporting information; experimental part
p. 188 - 194
(2011/03/21)
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- A direct stereoselective approach to trans-2,3-disubstituted piperidines: Application in the synthesis of 2-Epi-CP-99,994 and (+)-epilupinine
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(Chemical Equation Presented) A simple synthesis of enantiomerically pure piperidine esters is described, offering a straightforward access to the trans-2,3-disubstituted piperidine skeleton which is present in a broad range of biologically active compounds.
- Ahari, M'Hamed,Perez, Amandine,Menant, Christine,Vasse, Jean-Luc,Szymoniak, Jan
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supporting information; experimental part
p. 2473 - 2476
(2009/05/27)
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- Epimerization of lupinine to epilupinine and vice versa. Reexamination of the structures of lupinal and epilupinal
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Although the epimerization of lupinine (1) has been largely investigated, a previously not observed compound of formula C10H17NO was now isolated from the mixture of alkaloids that remains after the separation of epilupinine (2). It is insoluble in dry Et2O but soluble in EtOH, from which it is recovered as an Et2O-soluble oil that slowly returns to the Et2O-insoluble solid form. For these characteristics and based on GC/MS, 1H-NMR, and IR data, it is considered as the inner salt 6 of the common enolic form 5 of lupinal (3) and epilupinal (4), with which it is in equilibrium when standing in solution (see Scheme 1). The oily form, but not the solid one, is able to improve the conversion of 1 to 2, establishing the role of the aldehydes in the epimerization process. It was observed that also 2 can be converted to 1. Finally, the solid lupinal described by Zaboev should be considered as being identical to the now isolated inner salt 6, while the oily epilupinal of Wicky and Schumann is, indeed, a mixture of epilupinal (4) with a minor amount of lupinal (3), which, on standing, is converted to the inner salt 6 of the common enolic form 5.
- Sparatore, Anna,Tasso, Bruno,Boido, Vito,Sparatore, Fabio
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p. 245 - 251
(2007/10/03)
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- Double ring-closing metathesis reaction of nitrogen-containing tetraenes: Efficient construction of bicyclic alkaloid skeletons and synthetic application to four stereoisomers of lupinine and their derivatives
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The double ring-closing metathesis reaction of nitrogen-containing tetraenes was studied. The selectivity of the fused/dumbbell-type products can be controlled by the electronic/steric effects of the substituents attached to the C=C bonds and the s-cis/s-trans conformational ratios of the substrates. This methodology has also been successfully applied to the enantioselective synthesis of four stereoisomers of lupinine and their derivatives.
- Ma, Shengming,Ni, Bukuo
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p. 3286 - 3300
(2007/10/03)
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- Radical cyclizations of 1,4-dihydropyridines. Synthesis of chiral fused nitrogen heterocycles. Synthesis of lupinine and epilupinine
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Radical cyclizations of 1-(4-iodoalkanoyl)-3-formyl-4-methyl-l,4- dihydropyridines are described and discussed. A regio and diasteroselective reaction is obtained under ultrasonic conditions. An application to the synthesis of lupinine and epilupinine is shown.
- Mangeney, Pierre,Hamon, Louis,Raussou, Sabine,Urbain, Nicolas,Alexakis, Alexandre
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p. 10349 - 10362
(2007/10/03)
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- Asymmetric total synthesis of (-)-lupinine and (+)-epilupinine via α-sulfinyl ketimine. Stereocontrolled reduction of β-sulfinyl enamines
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(-)-Lupinine and (+)-epilupinine [(1R,9aR)- and (1S,9aR)-octahydro-1-hydroxymethyl-2H-quinolizine] were synthesized from (+)-2,3,4,5-tetrahydro-6-[(R)-(4-methylphenyl)sulfinylmethyl]pyridine (4) in five steps. The intermediate, 3,4,6,7,8,9-hexahydro-1-[(R)-(4-methylphenyl)sulfinyl]-2H-quinolizine (7), was stereoselectively reduced with cerium(III) chloride heptahydrate and sodium borohydride to give predominantly C-9a-R isomers, (9aR)-octahydro-1-[(R)-(4-methylphenyl)sulfinyl]-2H-quinolizines.
- Hua,Miao,Bravo,Takemoto
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p. 970 - 974
(2007/10/02)
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