Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

Abstract

SummaryThe tetrahydroquinolines obtained through the Povarov multicomponent reaction have been oxidized to the corresponding quinoline, giving access to a single product through a two-step sequence. Several oxidizing agents were studied and manganese dioxide proved to be the reagent of choice, affording higher yields, cleaner reactions and practical protocols.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: Synthesis, pharmacological evaluation and mechanistic studies

“…These reactions afforded in moderate to good yields and 1:1 to 1.7:1 diastereomeric ratio the diastereomeric mixtures of cis-fused octahydronaphthyridines 6a-c, which were subjected to DDQ oxidation [12] to yield the lactams 9a-c in 73%, 5%, and 36% yield, respectively, after silica gel column chromatography purification. In an attempt to improve the yield of 9b, the oxidation of the mixture 6b with MnO 2 [13] instead of DDQ only afforded unreacted material and open-ring byproducts. Chemoselective reduction of lactams 9a-c with (EtO) 3 SiH under Zn(OAc) 2 catalysis [14] provided the desired benzonaphthyridines 10a-c in low to moderate (15-52%) yields.…”

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies

“…For the synthesis of hybrids 5a-d, we used as starting material the N-Boc-protected tetrahydrobenzo[h] [1,6]naphthyridine 6, readily available by a multicomponent Povarov reaction between dihydro-2H-pyridine under the catalysis of Sc(OTf) 3 in acetonitrile [12], followed by DDQ oxidation [13] of the resulting diastereomeric mixture of octahydrobenzo[h] [1,6]naphthyridines [10]. Saponification of ester 6, followed by treatment of the resulting carboxylate with an Et 2 O solution of HCl afforded the corresponding carboxylic acid, which was isolated as the naphthyridine hydrochloride.…”

The Chemically Synthesized Ageladine A-Derivative LysoGlow84 Stains Lysosomes in Viable Mammalian Brain Cells and Specific Structures in the Marine Flatworm Macrostomum lignano

“…Starting with the Pictet-Spengler reaction of histamine dihydrochloride and naphthalene-2-carbaldehyde, using potassium hydroxide as base in refluxing ethanol, [ 9 , 15 , 16 ] the resulting 4-(naphthalene-2-yl)-4,5,6,7-tetrahydro- 1H -imidazo[4,5- c ]pyridine 1 was obtained as a mixture of enantiomers in nearly quantitative yield after chromatographic purification. To keep the subsequent oxidation step as simple as possible, a dehydrogenation step with activated manganese (IV) oxide was chosen [ 17 , 18 ], which allowed easy separation of the dehydrogenating agent by filtration of the reaction mixture. Other prominent agents that are commonly used to dehydrogenate tetrahydropyridine rings to aromatic systems, such as chloranil, Pd/C or IBX [ 19 ], had disadvantages during the separation process and were therefore not considered for further optimization of the synthesis method.…”