Recent advances and prospects in the organocatalytic synthesis of quinazolinones

Abstract

Quinazolinone, a bicyclic compound, comprises a pyrimidine ring fused at 4´ and 8´ positions with a benzene ring and constitutes a substantial class of nitrogen-containing heterocyclic compounds on account of their frequent existence in the key fragments of many natural alkaloids and pharmaceutically active components. Consequently, tremendous efforts have been subjected to the elegant construction of these compounds and have recently received immense interest in synthetic and medicinal chemistry. The domain of synthetic organic chemistry has grown significantly over the past few decades for the construction of highly functionalized therapeutically potential complex molecular structures with the aid of small organic molecules by replacing transition-metal catalysis. The rapid access to this heterocycle by means of organocatalytic strategy has provided new alternatives from the viewpoint of synthetic and green chemistry. In this review article, we have demonstrated a clear presentation of the recent organocatalytic synthesis of quinazolinones of potential therapeutic interests and covered the literature from 2015 to date. In addition to these, a clear presentation and understanding of the mechanistic aspects, features, and limitations of the developed reaction methodologies have been highlighted.

Visible light-mediated synthesis of quinazolinones and benzothiadiazine-1,1-dioxides utilizing aliphatic alcohols

“…Recently, utilizing inexpensive alcohols as sustainable coupling partners, several transition metal-based protocols were developed for the synthesis of quinazolinones and benzothiadiazine-1,1-dioxides which are an important and versatile class of N-heterocycles. 1,2 Since the conventional coupling partners for the synthesis of these important scaffolds are hazardous and waste generating, 3,4 replacement of these coupling partners with alcohols is a viable alternative as alcohols are stable, non-toxic and easily available from renewable sources. 5 However, the majority of the reported methodologies employed benzyl alcohol derivatives which required high temperature and high base loading.…”

Visible-light-induced organophotocatalytic and singlet oxygen-initiated domino construction of 1,4-dihydropyridines, C-3 functionalized spiro[indoline-3,4′-pyridines] and C-11 functionalized spiro[indeno-[1,2-b]quinoxaline-11,4′-pyridines]

“…Owing to the broad-spectrum distribution of N-heterocycles in over 60% of the products in the market or pipeline manufactured by different chemical industries as agrochemicals, fine chemicals, pharmaceuticals, and drug candidates, the rapid access to N-heterocycles of synthetic and natural origin is extremely demanding. [1][2][3] Among various small N-heterocycles, 1,4-dihydropyridines (1, and their derivatives comprise a huge family of indispensable molecular frameworks and have recently attracted interest in the synthetic organic and medicinal chemistry fields due to their significant pharmacological activities 4,5 and resemblance to the NADH coenzyme, which has an important role in biological oxidation-reduction reactions in our cells. 6 Several commercially available drugs such as felodipine, nitrendipine, nifedipine, and isradipine (Fig.…”

“…1, A-D) possessing the 1,4-DHP moiety are well known for their anti-hypertensive, vasodilatory, cardiac depressant activities, etc. [7][8][9][10][11] Spirocyclic compounds, particularly spirooxindoles, that comprise a tetrahedral sp 3 -hybridized carbon atom at the C-3 position of an orthogonally shaped bicyclic structure have received increasing attention in drug discovery and development, besides their great potential in natural product and synthetic organic chemistry. [12][13][14] Owing to the presence of sp 3 hybridized quaternary stereocenters at the 3-position, spiroox- indoles are a prominent class of compounds that are responsible for a large family of pharmaceutically significant natural and synthetic drug candidates (Fig.…”

“…[7][8][9][10][11] Spirocyclic compounds, particularly spirooxindoles, that comprise a tetrahedral sp 3 -hybridized carbon atom at the C-3 position of an orthogonally shaped bicyclic structure have received increasing attention in drug discovery and development, besides their great potential in natural product and synthetic organic chemistry. [12][13][14] Owing to the presence of sp 3 hybridized quaternary stereocenters at the 3-position, spiroox- indoles are a prominent class of compounds that are responsible for a large family of pharmaceutically significant natural and synthetic drug candidates (Fig. 1, E-I) and provide an opportunity to advance many physicochemical parameters such as lipophilicity, solubility, and metabolic stability, compared to the corresponding monocyclic systems.…”

“…Consequently, several synthetic approaches, from the traditional Hantzsch 31 reaction to many more, have been devised to assemble 1,4-dihydropyridines (Scheme 1a). Alternatively, there are limited reports on the synthesis of 1,4-DHPs based on a four-component reaction of aldehydes, active methylene compounds, dialkyl acetylene dicarboxylates, and amines using various catalytic systems including piperidine, 32 Fe 3 O 4 @SiO 2 -NH 2 , 33 Y 2 O 3 /ZrO 2 , 34 [3,OTf, 35 KF/Al 2 O 3 , 36 CuI, 37 and Sm 2 O 3 /ZrO 2 , 38 and under catalyst-free conditions [39][40][41][42] (Scheme 1b & c 43,44 ). In spite of the tremendous features offered by the developed strategies, the requirements of transition metal catalysts, volatile organic solvents, lengthy and laborious work-up procedures, high energy input, harsh reaction conditions, limited functional group tolerance, and relatively low yields of products mark the shortcomings of the processes.…”