The Stereochemistry and Synthesis of the Lobinaline Ring System

Robison, Michael M.; Lambert, Bernard; Dorfman, Louis; Pierson, William G.

doi:10.1021/jo01348a029

“…GC-MS analysis of the CHCl 3 sub-fraction revealed lobinaline, the major alkaloid present in L. cardinalis , as the most abundant constituent (AUC = 70.15%) of the sub-fraction [50, 76–79]. The identity of lobinaline, a complex binitrogenous alkaloid, was confirmed based on previously reported structural and MS data [50, 76, 78]. …”

Section: Resultssupporting

confidence: 68%

Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Brown

¹

,

Rogers

²

,

Pomerleau

³

et al. 2016

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In screening a library of plant extracts from ~1000 species native to the Southeastern United States, Lobelia cardinalis was identified as containing nicotinic acetylcholine receptor (nicAchR) binding activity which was relatively non-selective for the α4β2- and α7-nicAchR subtypes. This nicAchR binding profile is atypical for plant-derived nicAchR ligands, the majority of which are highly selective for α4β2-nicAchRs. Its potential therapeutic relevance is noteworthy since agonism of α4β2- and α7-nicAchRs is associated with anti-inflammatory and neuroprotective properties. Bioassay-guided fractionation of L. cardinalis extracts led to the identification of lobinaline, a complex binitrogenous alkaloid, as the main source of the unique nicAchR binding profile. Purified lobinaline was a potent free radical scavenger, displayed similar binding affinity at α4β2- and α7-nicAchRs, exhibited agonist activity at nicAchRs in SH-SY5Y cells, and inhibited [3H]-dopamine (DA) uptake in rat striatal synaptosomes. Lobinaline significantly increased fractional [3H] release from superfused rat striatal slices preloaded with [3H]-DA, an effect that was inhibited by the non-selective nicAchR antagonist mecamylamine. In vivo electrochemical studies in urethane-anesthetized rats demonstrated that lobinaline locally applied in the striatum significantly prolonged clearance of exogenous DA by the dopamine transporter (DAT). In contrast, lobeline, the most thoroughly investigated Lobelia alkaloid, is an α4β2-nicAchR antagonist, a poor free radical scavenger, and is a less potent DAT inhibitor. These previously unreported multifunctional effects of lobi-naline make it of interest as a lead to develop therapeutics for neuropathological disorders that involve free radical generation, cholinergic, and dopaminergic neurotransmission. These include neurodegenerative conditions, such as Parkinson’s disease, and drug abuse.

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“…[1][2][3][4][5] are consistent with the view that an intact C6-C2 unit, derived from phenylalanine, is incorporated into each of the two "halves" of lobinaline, in analogy with the mode of entry of the phenylalanine-derived fragment into sedamine (Scheme 1).…”

Section: Discussionsupporting

confidence: 65%

“…Lobinaline (I), the major alkaloid of this plant species, was isolated by Manske (2) in 1938. Its structure was determined some 30 years later (3,4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Visual dissection of its nucleus (dotted line) leads to two fragments, C6-C2-C,N, whose skeleton corresponds to that of some simpler Lobelia alkaloids, 8-phenylnorlobelol (4) (6) and 8-phenyllobelol (5) (6), which occur in Lobelia injiata. Even though such monomeric structures have not hitherto been found in L. cardinalis, the hypothesis is biogenetically attractive, that the lobinaline skeleton originates by dimerization of a suitably functionalized C6-C2-C,N monomer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biosynthesis of Lobinaline

Gupta¹,

Spenser²

1971

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The biosynthesis of lobinaline (1) in intact plants of Lobelia cardinalis L. was studied by tracer methods. The incorporation data are consistent with the view that the alkaloid is formed by dimerization of α-phenacylpiperidine (3), whose piperidine nucleus is derived from lysine via a nonsymmetrical intermediate, and whose sidechain originates, as an intact C6–C2 unit, from phenylalanine via cinnamic acid.

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Alkaloids

Mascavage

¹

,

Jasmin

²

,

Sonnet

³

et al. 2010

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Alkaloids Derived from Polyketides and the Amino Acids Ornithine and Lysine 2.1. Alkaloids Derived by the Insertion of Nitrogen into a Polyketide 2.1.1. ( S )‐(+)‐Coniine, γ‐Coniceine and Related Alkaloids 2.1.2. Solenopsin Family (Fire Ant Alkaloids) 2.1.3. Perhydroazaphenalenes: Defensive Alkaloids of the Coccinellidae 2.1.4. Cyanobacteria Alkaloids 2.1.5. Additional Polyketide‐Derived Alkaloids 2.2. Alkaloids Derived from Ornithine and/or Arginine 2.2.1. Tropane Alkaloids 2.2.2. Pyrrolizidine Alkaloids 2.3. Alkaloids Derived from Ornithine (and/or Arginine) and Nicotinic Acid 2.4. Alkaloids Derived from Lysine (Lys, K) and Nicotinic Acid 2.5. Purine Alkaloids 2.6. Imidazole Alkaloids 2.7. Pepper Alkaloids 3. Alkaloids Derived from the Shikimate Pathway 3.1. Alkaloids Derived from Anthranilate 3.2. Alkaloids Derived from Phenylalanine and Tyrosine 3.2.1. Biosynthesis of Dopamine, Mescaline and Capsaicin 3.2.2. Biosynthesis of Tetrahydroisoquinoline Alkaloids 3.2.3. Cryptostyline (Orchidaceae) and Alkaloids of the Amaryllidaceae 3.2.4. Ephedra Alkaloids 3.3. Alkaloids Derived from Tyrosine 3.4. Alkaloids Derived from Tryptophan and/or Tryptamine (Indole Alkaloids) 3.4.1. Alkaloids Derived from Tryptamine and an Unrearranged Monoterpene Unit 3.4.2. Mold Metabolites 3.4.3. Ergot Alkaloids 3.4.4. Corynantheine–Heteroyohimbine Structural Types 3.4.5. Corynantheine‐Type Alkaloids 3.4.6. Ajmalicine‐Type Alkaloids 3.4.7. Heteroyohimbine Oxindole Type 3.4.8. Glucoalkaloids 3.4.9. Yohimbine–Reserpine Structural Types 3.4.10. Akuammidine–Quebrachidine–Ervatamine–Gelsemine–Akuammiline Structural Types 3.4.11. Uleine–Ellipticine–Vallesamine–Ngouniensine Structural Types 3.5. The Cinchona Structural Type 3.6. The Camptothecin Structural Type 3.7. Terpene, Sesquiterpene, Diterpene and Steroidal Alkaloids (→ ((anchor interlink a26_205.xml Terpenes))) 3.7.1. Overview of Terpenoid Biosynthesis 3.7.2. Monoterpene Alkaloids 3.7.3. Sesquiterpene Alkaloids 3.7.4. Diterpene Alkaloids 3.7.5. Sesterterpene and Triterpene Alkaloids 3.7.6. Steroidal Alkaloids 4. Summary

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The Stereochemistry and Synthesis of the Lobinaline Ring System

Cited by 8 publications

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Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis

Biosynthesis of Lobinaline

Alkaloids

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