486-70-4Relevant articles and documents
An efficient asymmetric synthesis of (-)-lupinine
Davies, Stephen G.,Fletcher, Ai M.,Foster, Emma M.,Houlsby, Ian T. T.,Roberts, Paul M.,Schofield, Thomas M.,Thomson, James E.
, p. 8309 - 8311 (2014/07/22)
The asymmetric synthesis of (-)-lupinine was achieved in 8 steps, 15% overall yield and >99:1 dr from commercially available starting materials. The strategy used for the construction of the quinolizidine scaffold involved reaction of an enantiopure terti
Synthesis and comparison of antiplasmodial activity of (+), (-) and racemic 7-chloro-4-(N-lupinyl)aminoquinoline
Rusconi, Chiara,Vaiana, Nadia,Casagrande, Manolo,Basilico, Nicoletta,Parapini, Silvia,Taramelli, Donatella,Romeo, Sergio,Sparatore, Anna
, p. 5980 - 5985 (2012/11/06)
Recently the N-(-)-lupinyl-derivative of 7-chloro-4-aminoquinoline ((-)-AM-1; 7-chloro-4-{N-[(1S,9aR)(octahydro-2H-quinolizin-1-yl)methyl]amino} quinoline) showed potent in vitro and in vivo activity against both Chloroquine susceptible and resistant strains of Plasmodium falciparum. However, (-)-AM-1 is synthesized starting from (-)-lupinine, an expensive alkaloid isolated from Lupinus luteus whose worldwide production is not sufficient, at present, for large market purposes. To overcome this issue, the corresponding racemic compound, derived from synthetic (±)-lupinine was considered a cheaper alternative for the development of a novel antimalarial agent. Therefore, the racemic and the 7-chloro-4-(N-(+)-lupinyl)aminoquinoline ((±)-AM-1; (+)-AM-1) were synthesized and their in vitro antimalarial activity and cytotoxicity compared with those of (-)-AM-1. The (+)-lupinine required for the synthesis of (+)-AM-1 was obtained through a not previously described lipase catalyzed kinetic resolution of (±)-lupinine. In terms of antimalarial activity, (±)-AM1 and (+)-AM1 demonstrated very good activity in vitro against both CQ-R and CQ-S strains of P. falciparum (range IC50 16-35 nM), and low toxicity against human normal cell lines (therapeutic index >1000), comparable with that of (-)-AM1. These results confirm that the racemate (±)-AM1 could be considered as a potential antimalarial agent, ensuring a decrease of costs of synthesis compared to (-)-AM1.
Short total synthesis of (-)-lupinine and (-)-epiquinamide by double Mitsunobu reaction
Santos, Leonardo Silva,Mirabal-Gallardo, Yaneris,Shankaraiah, Nagula,Simirgiotis, Mario J.
, p. 51 - 56 (2011/02/26)
Alternative total syntheses of (-)-lupinine (1) and (-)-epiquinamide (2) have been described via the key intermediate 3 obtained from the addition of 2-trialkylsilyloxyfuran 5 to N-acyliminium intermediate derived from 4. The major R,R-isomer 8 obtained from the Mannich reaction was converted into its R,S-isomer through Mitsunobu reaction. Then, a second Mitsunobu reaction of 3 led to cyano 9 and azido 11 derivatives, which were converted into 1 and 2 in 33 and 36% overall yield from 4, respectively. The synthetic route is amenable for the generation of several quinolizidine alkaloids. Georg Thieme Verlag Stuttgart · New York.
Organocatalytic enantioselective synthesis of quinolizidine alkaloids (+)-myrtine, (-)-lupinine, and (+)-epiepiquinamide
Fustero, Santos,Moscardó, Javier,Sánchez-Roselló, María,Flores, Sonia,Guerola, Marta,Pozo, Carlos Del
experimental part, p. 7412 - 7417 (2011/10/09)
The organocatalytic synthesis of quinolizidine alkaloids (+)-myrtine, (-)-lupinine, and (+)-epiepiquinamide is described. It involved, as the key step, an enantioselective intramolecular aza-Michael reaction (IMAMR) catalyzed by J?rgensen catalyst I, affording the common precursor with high enantioselectivity. This compound was subsequently transformed into the three alkaloids in a highly diastereoselective manner.
Convenient one-pot synthesis of chiral tetrahydropyridines via a multicomponent reaction
Noel, Romain,Fargeau-Bellassoued, Marie-Claude,Vanucci-Bacque, Corinne,Lhommet, Gerard
experimental part, p. 1948 - 1954 (2009/04/04)
The multicomponent condensation of various β-dicarbonyl compounds, acrolein and (S)-2-phenylglycinol was found to provide a one-pot access to chiral 6-carbonyl-3-phenyl-2,3,8,8a-tet-rahydro-7H-[l,3]oxazolo[3,2-a]pyridines. The value of this methodology is illustrated by the short and efficient synthesis of (-)-lupinine.
Epimerization of lupinine to epilupinine and vice versa. Reexamination of the structures of lupinal and epilupinal
Sparatore, Anna,Tasso, Bruno,Boido, Vito,Sparatore, Fabio
, p. 245 - 251 (2007/10/03)
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.
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
Ma, Shengming,Ni, Bukuo
, p. 3286 - 3300 (2007/10/03)
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.
Enantioselective synthesis of indolizidine and quinolizidine derivatives from chiral non-racemic bicyclic lactams
Agami, Claude,Dechoux, Luc,Hebbe, Séverine,Ménard, Cécilia
, p. 5433 - 5438 (2007/10/03)
Chiral non-racemic bicyclic lactams 2b,c, derived from (R)- and (S)-phenylglycinol, were used in the enantioselective synthesis of (-)-lupinine and 5-epitashiromine, respectively. The efficiency of the synthesis relied on the high diastereoselectivities of formation and reduction of compounds 2b,c.
Syntheses from chiral heterocyclic β-amino esters. A new versatile access to pyrrolizidine and quinolizidine alkaloids
Ledoux, Stéphane,Marchalant, Elisabeth,Célérier, Jean-Pierre,Lhommet, Gérard
, p. 5397 - 5399 (2007/10/03)
Chiral heterocyclic β-amino esters can be easily transformed into bicyclic alkaloids after a diastereoselective alkylation followed by specific chemical transformations.
Radical cyclizations of 1,4-dihydropyridines. Synthesis of chiral fused nitrogen heterocycles. Synthesis of lupinine and epilupinine
Mangeney, Pierre,Hamon, Louis,Raussou, Sabine,Urbain, Nicolas,Alexakis, Alexandre
, p. 10349 - 10362 (2007/10/03)
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.
