Verfahren zur Darstellung von 4‐Oxo‐1,4‐dihydropyridincarbonsäurederivaten

Abstract

Durch basenkatalysierte, intramolekulare Kondensation der Michaeladdukte 1 aus homooder heteroaroniatischen o-Aminocarbonsaureestern und AcetylendicarbonsLureestern werden aromatisch anellierte 4-0~0-1,4-dihydr0-2,3-pyridindicarbonsaureester 2 erhalten. Diese konnen durch regioselektive Verseifung und Decarboxylierung in die entsprechenden 443x0-1,4-dihydr0-3-pyridincarbonsauren umgewandelt werden.A General Synthesis of 4-0x0-I ,4-dihydropyridinecarboxylic Acid Derivatives Homo-or heteroaromatically annelated esters of 4-0x0-I ,4-dihydro-2,3-pyridinedicarboxylic acids 2 are easily obtained by base catalyzed intramolecular cyclization o€ the Michael adducts 1 prepared from the corresponding aromatic o-amino esters and dialkyl acetylenedicarboxylates. Successive regioselective hydrolysis and decarboxylation leads to the corresponding 4-0x0-~,4-dihydro-3-pyridinecarboxylic acids.Homo-oder heteroaromatisch anellierte 4-0x0-I ,4-dihydro-3-pyridincarbonsaurederivate 6 (Schema I , 612, g, h und i) sind in der Arzneimittelchemie wegen ihrer antibakteriellen Aktivitat interessant2-5), wahrend anellierte 4-0xo-1,2-dihydro-2-pyridincarbonsaurederivate friiher wegen antiparasitarers) und neuerdings auch wegen antiallergischer Wirkung7) Beachtung finden. Neben den klassischen Verfahren, z. B. Conrad-Limpach-Reaktiori 6 8 ) sowie Niementowski-Reaktion 9. lo), die sich mehr oder weniger gut zur Synthese von 4-0x0-I ,4-dihydrochinolin-2-oder -3-carbonsaurederivaten eignen, wurde die Gould-Jacobs-Reaktion11) besonders haufig zur Synthese der Verbindungen 6 angewendet.

Nucleophilic β-Oniovinylation: Concept, Mechanism, Scope, and Applications

“…Unfortunately, methyl 3-(trimethylsilyl)propiolate (Z ) TMS) did not undergo any vinylonio reaction. Yet, as the decarboxylation of quinolones of type 32 at C2 is known from the literature to be simple and highly effective, 12 the above-mentioned method provides a novel synthetic approach to modern fluoroquinolone antibiotics (which bear a hydrogen substituent at C2 as well as a carboxy group at C3). These constitute the most important class of antiobiotics used today, curing a wide variety of diseases.…”

From Hit to Lead: De Novo Design Based on Virtual Screening Hits of Inhibitors of tRNA‐Guanine Transglycosylase, a Putative Target of Shigellosis Therapy

“…Analogously to the three-step synthesis of 1, from methyl 2-aminobenzoate (5.0 mmol) (see also [38] (7)). Analogously to the three-step synthesis of 4, from methyl 5-hydroxy-2-aminobenzoate (1.6 mmol).…”

Synthesis of Novel Halogenated 4(1H)-Quinolones by Thermolysis of Arylaminomethylene-1,3-dioxane-4,6-diones

“…Antimicrobial 4(1H)-quinolones norfloxacin (Norfluxx ® ) and ciprofloxacin (Ciprobay ® ) Classic syntheses of 4(1H)-quinolones rely on the addition of (ethoxymethylene)malonates with anilines and subsequent cyclization 8 and on the addition of maleates to o-aminobenzoates and subsequent cyclization. 9 However, these methods are not suitable for the synthesis of 2,3-un-substituted 4(1H)-quinolones as the ester groups present at these positions have to be removed in several steps. Heindel et al reported 10 and elegant approach to 4(1H)quinolones by nucleophilic addition of anilines to methyl acetylenecarboxylate and subsequent cyclization.…”