(+)-Sparteine

Sustainable Asymmetric Organolithium Chemistry: Enantio- and Chemoselective Acylations through Recycling of Solvent, Sparteine, and Weinreb "Amine".[Pubmed:30614208]

ChemSusChem. 2019 Mar 21;12(6):1147-1154.

The well-established Hoppe-Beak chemistry, which involves enantioselective generation of organolithium compounds in the presence of (-)-sparteine, was revisited and applied to unprecedented acylations with Weinreb amides to access highly enantioenriched alpha-oxyketones and cyclic alpha-aminoketones. Recycling of the sustainable solvent cyclopentyl methyl ether, sparteine, and the released Weinreb "amine" [HNMe(OMe)] was possible through a simple work-up procedure that enabled full recovery of these precious materials. The methodology features a robust scope and flexibility, thus allowing the enantioselective preparation of scaffolds amenable of further derivatization.

17 Oxo Sparteine and Lupanine, Obtained from Cytisus scoparius, Exert a Neuroprotection against Soluble Oligomers of Amyloid-beta Toxicity by Nicotinic Acetylcholine Receptors.[Pubmed:30584148]

J Alzheimers Dis. 2019;67(1):343-356.

Alzheimer's disease (AD) is a neurodegenerative pathology, which is characterized by progressive and irreversible cognitive impairment. Most of the neuronal perturbations described in AD can be associated with soluble amyloid- beta oligomers (SO-Abeta). There is a large amount of evidence demonstrating the neuroprotective effect of Nicotine neurotransmission in AD, mainly through nicotinic acetylcholine receptor (nAChR) activation and antiapoptotic PI3K/Akt/Bcl-2 pathway signaling. Using HPLC and GC/MS, we isolated and characterized two alkaloids obtained from C. scoparius, Lupanine (Lup), and 17- oxo-sparteine (17- ox), and examined their neuroprotective properties in a cellular model of SO-Abeta toxicity. Our results showed that Lup and 17- ox (both at 0.03muM) prevented SO-Abeta-induced toxicity in PC12 cells (Lup: 64+/-7%; 17- ox: 57+/-6%). Similar results were seen in hippocampal neurons where these alkaloids prevented SO-Abeta neurotoxicity (Lup: 57+/-2%; 17- ox: 52+/-3%) and increased the frequency of spontaneous calcium transients (Lup: 60+/-4%; 17- Ox: 40+/-3%), suggesting an enhancing effect on neural network activity and synaptic activity potentiation. All of the neuroprotective effects elicited by both alkaloids were completely blocked by alpha-bungarotoxin. Additionally, we observed that the presence of both Lup and 17- ox increased Akt phosphorylation levels (52+/-4% and 35+/-7%, respectively) in cells treated with SO-Abeta (3 h). Taken together, our results suggest that the activation of nAChR by Lup and 17- ox induces neuroprotection in different cellular models, and appears to be an interesting target for the development of new pharmacological tools and strategies against AD.

Genome Sequence Analysis of Two Pseudomonas putida Strains to Identify a 17-Hydroxylase Putatively Involved in Sparteine Degradation.[Pubmed:30267141]

Curr Microbiol. 2018 Dec;75(12):1649-1654.

Two strains of Pseudomonas putida, Psp-LUP and Psp-SPAR, capable of growth on the quinolizidine alkaloids, lupanine and sparteine respectively, were studied here. We report the isolation of Psp-SPAR and the complete genome sequencing of both bacteria. Both were confirmed to belong to P. putida, Psp-LUP close to the type isolate of the species (NBRC14164(T)) and Psp-SPAR close to strains KT2440 and F1. Psp-SPAR did not grow on lupanine but did contain a gene encoding a putative quinolizidine-17-hydroxylase peptide which exhibited high similarity (76%identity) to the lupanine-17-hydroxylase characterised from Psp-LUP.

Gram-Scale Synthesis of the (-)-Sparteine Surrogate and (-)-Sparteine.[Pubmed:29155468]

Angew Chem Int Ed Engl. 2018 Jan 2;57(1):223-226.

An 8-step, gram-scale synthesis of the (-)-sparteine surrogate (22 % yield, with just 3 chromatographic purifications) and a 10-step, gram-scale synthesis of (-)-sparteine (31 % yield) are reported. Both syntheses proceed with complete diastereocontrol and allow access to either antipode. Since the syntheses do not rely on natural product extraction, our work addresses long-term supply issues relating to these widely used chiral ligands.

C2-Modified Sparteine Derivatives Are a New Class of Potentially Long-Acting Sodium Channel Blockers.[Pubmed:29045055]

ChemMedChem. 2017 Nov 22;12(22):1819-1822.

The lupin alkaloid sparteine is a well-known chiral diamine with a range of applications in asymmetric synthesis, as well as a blocker of voltage-gated sodium channels (VGSCs). However, there is only scarce information on the VGSC-blocking activity of sparteine derivatives where the structure of the parent alkaloid is retained. Building on the recent renewed availability of sparteine and derivatives we report herein how modification of sparteine at position 2 produces irreversible blockers of VGSCs. These compounds could be clinically envisaged as long-lasting local anesthetics.

Rotational spectra of tetracyclic quinolizidine alkaloids: does a water molecule flip sparteine?[Pubmed:28474045]

Phys Chem Chem Phys. 2017 Jul 21;19(27):17553-17559.

Sparteine is a quinolizidine alkaloid used as a chiral auxiliary in asymmetric synthesis. We examine whether hydration by a single molecule can flip sparteine from the most stable trans conformation to the bidentate cis arrangement observed in catalytic complexation to a metal center. Sparteine and the sparteine-water dimer were generated in a supersonic jet expansion with H2(16)O and H2(18)O, and characterized by broadband chirped-pulse microwave spectroscopy. Even though the bidentate water dimer was predicted with larger binding energy, a single isomer was observed for the monohydrated cluster, with sparteine retaining the trans conformation observed for the free molecule. The absence of the bidentate dimer is attributed to the kinetic control of cluster formation, favoring the pre-expansion most abundant monomer. The structural properties of the O-HN hydrogen bond in the dimer are compared with those of complexes of other secondary and tertiary amines.

(+)-Sparteine is a natural alkaloid acting as a ganglionic blocking agent. (+)-Sparteine competitively blocks nicotinic ACh receptor in the neurons.

(+)-Sparteine,492-08-0,Natural Products, buy (+)-Sparteine , (+)-Sparteine supplier , purchase (+)-Sparteine , (+)-Sparteine cost , (+)-Sparteine manufacturer , order (+)-Sparteine , high purity (+)-Sparteine