221664-11-5Relevant academic research and scientific papers
Strategies for the Asymmetric Construction of Pelletierine and its Use in the Synthesis of Sedridine, Myrtine, and Lasubine
Zaidan, Raed K.,Evans, Paul
, p. 5354 - 5367 (2019/06/25)
Three methods for the asymmetric synthesis of both enantiomers of pelletierine 6 are reported. Bella's proline-based Mannich process gave (R)- and (S)-Cbz-protected 6 in good yields from Δ1-piperideine 14 and in reasonable enantiomeric excess (74–80 % ee). An intramolecular aza-Michael, cinchona-based, organocatalytic method is also reported. With commercially available 9-amino quinine (24a) and quinidine (24b) catalysts, Cbz-protected α,β-unsaturated ketone 23 also gave (R)- and (S)-Cbz-protected 6 in good yields and enantiomeric excess (90–99 % ee). This material was used to synthesize both optically active forms of deoxyhalofuginone (26), an analogue of febrifugine which is of interest as an anti-fibrotic agent. Finally, a resolution of racemic pelletierine using (R)- and (S)-mandelic acid 27 is reported. This scalable method gave both enantiomers of Cbz- and Boc-protected 6 in excellent enantiomeric excess (≥ 99 %). Both highly enantioenriched forms of 6 (obtained from the resolution study) were used to synthesize several alkaloids. Firstly, (–)-(S)-Cbz-protected pelletierine 17 was used to prepare naturally occurring sedridine (32) and its epimer allosedridine (8). Then the preparation of both enantiomers of the quinolizidine myrtine (33) by an olefination-intramolecular aza-Michael sequence is reported. Finally, the synthesis of the epimeric quinolizidine alkaloids, lasubine I (34) and lasubine II (35), from (+)- and (–)-Boc-protected pelletierine (29) respectively, is discussed.
Biomimetic Organocatalytic Approach to 4-Arylquinolizidine Alkaloids and Application in the Synthesis of (-)-Lasubine II and (+)-Subcosine II
Virk, Seerat,Pansare, Sunil V.
supporting information, p. 5524 - 5528 (2019/07/08)
An enantioselective, biomimetic organocatalytic synthesis of 4-arylquinolizidin-2-ones, key intermediates in the synthesis of several Lythraceae alkaloids, was developed. The methodology features S-proline-mediated Mannich/aza-Michael reactions of readily available arylideneacetones and Δ1-piperideine. The total syntheses of (-)-lasubine II and (+)-subcosine II as well as the formal syntheses of structurally related Lythraceae alkaloids were achieved. The use of Δ1-pyrroline in the Mannich/aza-Michael reaction provides enantiomerically enriched 5-arylindolizidin-7-ones, which are precursors to nonopiate antinociceptive agents.
Enantiodivergent Approach to the Synthesis of Cis-2,6-Disubstituted Piperidin-4-ones
Lahosa, Alejandro,Yus, Miguel,Foubelo, Francisco
, p. 7331 - 7341 (2019/06/14)
Enantiopure β-amino ketone derivatives were synthesized by decarboxylative Mannich reaction of chiral N-tert-butanesulfinyl imines with β-keto acids and were subsequently transformed into cis-2,6-disubstituted piperidin-4-ones through an organocatalyzed condensation with aldehydes. Both enantiomers were accessible from the same precursors by inverting the order in the reaction sequence of the aldehydes involved in the imine formation and the intramolecular Mannich condensation. The synthesis of the piperidine alkaloids (+)-241D, (-)-epimyrtine, and (-)-lasubine II demonstrated the utility of this methodology.
Broad Spectrum Enolate Equivalent for Catalytic Chemo-, Diastereo-, and Enantioselective Addition to N-Boc Imines
Trost, Barry M.,Hung, Chao-I
, p. 15940 - 15946 (2016/01/09)
Alkynyl ketones are attractive but challenging nucleophiles in enolate chemistry. Their susceptibility to other reactions such as Michael additions and the difficulty of controlling the enolate geometry make them difficult substrates. Mannich-type reactions, which previously have not been reported using N-carbamoyl-imines with simple ketone enolates, became our objective. In this report, we describe the first direct catalytic Mannich-type reaction between various ynones and N-Boc imines, whose stereocontrol presumably derives from catalyst control of enolate geometry. This method produces α-substituted β-amino ynones with excellent chemo-, diastereo-, and enantioselectivity. The products can be readily transformed into a broad range of molecular scaffolds upon further one-step transformations, demonstrating the utility of ynones as masked synthetic equivalents for a variety of unsymmetrically substituted acyclic ketones. In particular, alkynyl alkyl ketones resolve the long-standing problem of the inability to use the enolates of unsymmetrical dialkyl ketones lacking α-branching for regio- and stereoselective reactions.
Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
, p. 17019 - 17022,4 (2012/12/12)
A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors
Shi, Shi-Liang,Wei, Xiao-Feng,Shimizu, Yohei,Kanai, Motomu
, p. 17019 - 17022 (2013/01/15)
A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Bronsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.
Total synthesis of (±)-decinine via an oxidative biaryl coupling with defined axial chirality
Shan, Zhen-Hua,Liu, Ji,Xu, Ling-Min,Tang, Ye-Feng,Chen, Jia-Hua,Yang, Zhen
, p. 3712 - 3715 (2012/09/21)
The total synthesis of (±)-decinine has been achieved. The key steps in the synthesis involved the formation of lasubine II via a gold catalyzed annulation of 1-(but-3-yn-1-yl)piperidine and the formation of the 12-membered ring of decinine (1) with complementary atropselectivity via a VOF 3-mediated oxidative biaryl coupling reaction.
Preparation of enantiopure substituted piperidines containing 2-alkene or 2-alkyne Chains: Application to total syntheses of natural quinolizidine- alkaloids
Cheng, Guolin,Wang, Xinyan,Su, Deyong,Liu, Hui,Liu, Fei,Hu, Yuefei
supporting information; experimental part, p. 1911 - 1916 (2010/06/15)
"Chemical Equation Presented" A general method, for the preparation of enantiopure 2-alkene- or 2-alkyne-containing chain substituted piperidines was established by using nonracemic Betti base as a chiral auxiliary. The key step is that the auxiliary residue was removed by a novel base-catalyzed N-debenzylation via a formation of o-quinone methide mechanism in stead, of the traditional hydrogenolysis, by which the alkene or alkyne groups survived. By this method, ten 2-alkene- or 2-alkyne-containing chain substituted piperidines were prepared on the gram scale within a few hours. To demonstrate the efficiency of the method and the versatility of the product, total, syntheses of natural alkaloids (+)-pelletierine((-)-lasubine II, and (-)-cermizine C were achieved by using (S)-2-allyl-N-Bocpiperidine as a versatile building block.
Stereoselective synthesis of quinolizidine alkaloids: (-)-Lasubin II
Weymann, Markus,Kunz, Horst
experimental part, p. 425 - 430 (2009/01/31)
Based on a higly diastereoselective Mannich reaction of N-(3,4-dimethoxybenzylidene) 2,3,4,6-tetra-O-pivaloyl-β-D- galactopyranosylamine 3 with the Danishefsky diene the quinolizidine alkaloid lasubin II was synthesized in enantiomerically pure form in six steps.
Concise enantioselective synthesis of (-)-lasubine II
Zaja, Mirko,Blechert, Siegfried
, p. 9629 - 9634 (2007/10/03)
An enantioselective synthesis of the quinolizidine alkaloid (-)-lasubine II 1 is reported. Two different pathways to the key intermediate 2 are described. The first case involving a sequence of ring rearrangement metathesis (RRM), simple functional group interconversion operations, followed by a stereoselective cross metathesis (CM) and in the second case a domino ring opening-/ring closing-/cross metathesis step is involved. In both cases, following the metathesis reactions, exclusively the E-isomer was obtained. The final cyclisation towards the quinolizidine skeleton is achieved by an intramolecular Michael reaction. This concept represents the first example of a highly stereoselective RRM-CM combination in the synthesis of a natural product. Graphical Abstract.
