“Diversity Oriented Synthesis” of Functionalized Chiral Tetrahydropyridines: Potential GABA Receptor Agonists and Azasugars from Natural Amino Acids via a Sequential Baylis−Hillman Reaction and RCM Protocol

Abstract

The preparation of chiral tetrahydropyridine-4-carboxylates as isoguvacine analogues and azasugars with a tertiary stereocenter from L-amino acids via diastereoselective a Baylis-Hillman reaction of N-allyl-Boc alpha-aminal, followed by ring-closing metathesis and dihydroxylation sequences, is reported.

Tetrahydropyridine: a promising heterocycle for pharmacologically active molecules

“…95 They have the potential to be used as anticancer, antiviral, and antidiabetic agents. 97 Ethyl 1,6-dimethyl-3-oxo-5phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate (compound 107) is a derivative of secoergoline that exhibited the inhibition of uptake of GABA (IC 50 = 680 ± 87 µ M) and glutamine (IC 50 = 660 ± 61 µ M) through cerebrocortical membranes specifically. The inhibition of uptake of GABA (IC 50 = 3.7 ± 0.6 µ M, 360 ± 8 µ M) and glutamine (IC 50 = 9 ± 0.2 nM, 591 ± 24 µ M) was more effective in the presence of a known inhibitor of these neurotransmitters and took place in two phases.…”

Silver, iron, and nickel immobilized on hydroxyapatite‐core‐shell γ‐Fe2O3 MNPs catalyzed one‐pot five‐component reactions for the synthesis of tetrahydropyridines by tandem condensation of amines, aldehydes, and methyl acetoacetate

“…Tetrahydropyridine and their derivatives possess a broad spectrum of pharmacological and biological activities. For example, these compounds have been frequently used as antibacterial, antimalarial, oral antagonistic, neurotoxic activity, antihypertensive, GABA receptor, and anticonvulsant and antiinflammatory agents . Furthermore, these compounds are used as therapeutic agents such as bamipine, ɑ‐methylfentanyl, cisapride, fentanyl, clebopride, and indoramine .…”

Diastereoselective synthesis and molecular docking studies of novel fused tetrahydropyridine derivatives as new inhibitors of HIV protease

“…In addition, the tetrahydropyridine ring system is a widely distributed structural framework that is involved in a number of pharmaceuticals ---and natural products, [4] , [5] such as, Haouamine A, and B, isolated from the ascidian Aplidium haourianum, [6] (-)-grandisine G, isolated from an Australian rainforest tree Elaeocarpus grandis, which was found to show potent activity in the human σ-opioid receptor binding affinity, [7] and Lysergic acid. [8] Furthermore, during the last decade, such compounds have shown interesting pharmacological properties like anti-inflammatory, [9] antimycobacterial, [10] antimalarials, [11] dopamine D1 receptor, [12] GABA, [13] and CB1 receptors. [14] (Fig.…”