Synthesis of Biologically Active Molecules through Multicomponent Reactions

Abstract

Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

Consecutive Three‐Component Coupling‐Addition Synthesis of β‐Amino Enoates and 3‐Hydroxypyrazoles via Ethyl 3‐Arylpropiolates

“…Multicomponent reactions (MCR) are a reactivity‐based concept, where more than two bonds are formed from more than two compounds in a one‐pot reaction. This implies a plethora of advantages in sustainability and selectivity, whereby these reactions appear to be impeccable for the construction of structures with high diversity, in particular, biologically active molecules . The vast majority of these compounds are heterocycles and, therefore, highly efficient and efficacious concise syntheses, such as MCR, are highly demanded.…”

Edible and Nutritive Electronics: Materials, Fabrications, Components, and Applications

“…Therefore, many synthetic strategies of these biopigments have been reported and reviewed, e.g., multicomponent reactions. [ 32 ]…”

Novel Methodologies for Chemical Activation in Organic Synthesis under Solvent-Free Reaction Conditions

“…Multicomponent reactions reflect also the state of the art in chemical control since generally C-C and C-X (X = heteroatom) bonds are formed in one single step. For recent interesting applications of mechanochemistry in multicomponent reactions see references [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ].…”