10248-30-3

Usage

Uses

(±)-Lupinine is used to the synthesis of calcium-channel antagonists.

Purification Methods

It crystallises from Me2CO, pentane and pet ether (b. 40-60o) and can be sublimed or distilled in high vacuum. The picrate has m 127o(from Et2O), the picrolonate has m 203-204o, and the methiodide has m 203o(dec, from EtOH). [Clemo et al. J Chem Soc 969 1937, Boekelheide & Lodge J Am Chem Soc 73 3684 1951, Beilstein 21 II 28, 21 III/IV 291.]

Upstream product

• 505-18-0 2,3,4,5-tetrahydropyridine 
• 127-09-3 sodium acetate 
• 5176-08-9 (+/-)-1t-bromomethyl-(9ar)-octahydro-quinolizin 
• 31436-28-9 methyl (1R^*,9aR^*)-1,2,3,6,7,8,9,9a-octahydro-4H-quinolizine-1-carboxylate 
• 102301-64-4 4-(3-Dimethylaminomethyl-1,1-dioxo-2,5-dihydro-1H-1λ⁶-thiophen-2-yl)-butyric acid tert-butyl ester 
• 675-20-7 piperidin-2-one 
• 858261-80-0 5-phenoxy-2-[2]piperidyl-pentan-1-ol 
• 101888-71-5 5-phenoxy-2-[2]piperidyl-valeric acid ethyl ester 
• 849334-35-6 1-(5-hydroxypentyl)-2-(4-methylphenylsulfonyl)acetamide 
• 916067-59-9 1-hydroxy-1-hydroxymethyl-3-trimethylsilanyl-1,6,7,8,9,9a-hexahydro-quinolizin-4-one 
• 916067-58-8 1-methylene-3-trimethylsilanyl-1,6,7,8,9,9a-hexahydro-quinolizin-4-one 
• 916067-52-2 1-methylene-3-trimethylsilanyl-1,6,7,8,9,9a-hexahydro-quinolizine-4-thione 
• 2130-68-9 Lupinal 
• 16100-91-7 cis carbethoxy-1 octahydro-1,2,3,6,7,8,9,10-4H-pyrido<1,2-a>pyridine 

Downstream Products

• 486-70-4 lupinine 
• 10248-22-3 (+/-)-N-Lupinyl-phthalimid 
• 2121-03-1 d,l-chlorolupinane 
• 10248-22-3 2-[(1S,9aR)-octahydro-2H-quinolizin-1-ylmethyl]-1H-isoindol-1,3(2H)-dione 

Relevant academic research and scientific papers

Syntheses of Isoretronecanol and Lupinine

Syntheses of (+/-)-isoretronecanol and (+/-)-lupinine are described which employ the 1,3-dipolar additions of cyclic nitrones to dihydrofuran and dihydropyran.The reaction proceeded regio- and stereoselectively to afford the adducts, which were converted into the title compounds by two-step processes.

β-ENAMINOESTERS BICYCLIQUES : SYNTHESE ET REDUCTION STEREOSPECEFIQUES. ACCES A L'ISORETRONECANOL, LA TRACHELANTHAMIDINE, LA LUPININE ET L'EPILUPININE

The functionalized N-alkyl-β-enaminoesters 11 are precursore of nitrogen-bridged bicyclic β-enaminoesters 7.The compounds 7 are prepared either by intramolecular alkylation of β-enaminoesters 11 or by termolysis of β-enaminoesters 6.A stereospecific reduction of 7 under thermal control leads to bicyclic β-aminoesters 13, 14, 15 or 16 which are good precursors of natural aminoalcohols like lupinine 4 or isoretronecanol 2.

Piperidine and azetidine formation by direct cyclization of diols with N-nonsubstituted sulfonamide under the Mitsunobu conditions utilizing (cyanomethylene)tributylphosphorane (CMBP) and its application to the synthesis of lupinine

(Cyanomethylene)tributylphosphorane (CMBP) can promote the Mitsunobu reaction of 1,3- and 1,5-diols with N-nonsubstituted sulfonamides, such as tosylamide (TsNH2) and 3,3-dimethoxypropylsulfonamide (DimpsNH2), to prepare azetidine and piperidine ring systems directly. Utilizing this methodology, lupinine, a biologically active piperidine alkaloid, was synthesized.

Synthesis of Substituted Quinolizidines via a Gold-Catalyzed Double Cyclization Cascade

A novel synthesis of quinolizidines by a cationic gold-catalyzed double cyclization cascade has been developed. The reaction was initiated by the gold-catalyzed 6-exo-dig cyclization of ynamides, which was followed by a second cyclization of an enamide intermediate to provide the corresponding quinolizidine derivatives. The utility of this reaction was demonstrated by application to the synthesis of multi-substituted quinolizidines and by the total synthesis of a quinolizidine alkaloid, (±)-lupinine.

A hydrozirconation/iodination-mediated access to tetrahydroquinolizinium salts. Application to the synthesis of Lupinine and (-)-Epiquinamide

The preparation of tetrahydroquinolizinium salts, based on a hydrozirconation/iodination sequence involving 2-pyridyl alkenes, is presented. This approach was applied to the synthesis of substituted quinolizines as illustrated by the synthesis of Lupinine

Synthesis and comparison of antiplasmodial activity of (+), (-) and racemic 7-chloro-4-(N-lupinyl)aminoquinoline

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.

A new strategy for the synthesis of (±)-Lupinine and (±)-epilupinine via cyclization of α-sulfinyl carbanions

(±)-Lupinine and (±)-epilupinine have been prepared starting from commercially available δ-valerolactam. The synthetic route involves the advantages of the cyclization based on α-sulfmyl carbanions.

Synthesis of δ-thiolactams by the aza-Diels-Alder reaction of in situ generated allenyltrimethylsilylthioketenes with imines

Allenyltrimethylsilylthioketenes, generated in situ through [3,3] sigmatropic rearrangement of trimethylsilylethynyl propargyl sulfides, underwent facile [4+2] cycloaddition with imines to afford the corresponding δ-thiolactams. The resulting 2-trimethylsilyl-4-methylenetetrahydroquinolidine-2-thione, obtained by the [4+2] cycloaddition using piperideine as a dienophile, was transformed into (±)-lupinine in six steps.

Synthesis of lupinine

A synthesis of lupinine (1a) is performed from 5-amino-1-pentanol in ten steps. The glutarimide (3) was obtained from 1-(5-hydroxypentyl)-2-(4-methylphenylsulfonyl)acetamide (5) and acrylate (4) via a formal [3+3] annulation. This formation of quinolizidi

Oxidative deamination of tetrahydroanabasine with o-quinones: An easy entry to lupinine, sparteine, and anabasine

A mild oxidative deamination reaction of tetrahydroanabasine O-methyloxime 17 is described, making use of an o-quinone that is based on topaquinone (TPQ, 11), the cofactor that is present in copper-containing amine oxidases. In situ ring closure of the oxidation product produced double functionalized quinolizidine 5, containing an enamine functionality with excellent reactivity. From this quinolizidine 5 a variety of biogenetically related lupin alkaloids were prepared: lupinine (7) and aminolupinane (8) via reductive sequences and sparteine (9) via a condensation reaction with dehydropiperidine 1. The configurationally more favorable trans isomers epilupinine (25) and β-isosparteine (10) were formed when more drastic reaction conditions were used for oxime hydrolysis. Anabasine (4) and a new 5-piperidylanabasine derivative 6 were formed by an unexpected acid catalyzed ring transformation reaction, whereby the pyridine ring was formed via oxime-induced aromatization. The stereochemistry of the reaction products and the biogenetic implications are discussed.