Novel synthesis and cytotoxic activity of 1,4-disubstituted 3-methylidene-3,4-dihydroquinolin-2(1H)-ones

Abstract

1,4-Disubstituted 3-methylidene-3,4-dihydroquinolin-2(1H)-ones were efficiently synthesized using a Horner–Wadsworth–Emmons approach and their cytotoxic activity was evaluated.

Synthesis of 3‐Methylidene‐1‐tosyl‐2,3‐dihydroquinolin‐4(1H)‐ones as Potent Cytotoxic Agents

“…In turn, ketones 10 were mixtures of cis and trans isomers and configurational assignments were made on the bases of characteristic 3 J (H2,H3) coupling constants, which were in the range of 4.4 – 4.6 Hz for cis isomers and 1.2 – 1.4 for trans isomers. Analogous differences in the 3 J (H3,H4) coupling constants in cis ‐ and trans ‐4‐substituted‐3‐phosphoryl‐2,3‐dihydroquinolin‐2(1 H )‐ones [ ][ ] and 4‐substituted‐3‐phosphorylchroman‐2‐ones [ ][ ] are well documented and were attributed to the trans ‐diaxial arrangement of the phosphoryl group and substituent in position 4 in trans ‐isomers. Inspection of the molecular models of cis ‐ and trans ‐3‐(diethoxyphosphoryl)‐2,3‐dihydroquinolin‐4(1 H )‐ones 10 revealed great conformational similarity of these compounds to 3‐phosphorylquinolin‐2‐ones and 3‐phosphorylchroman‐2‐ones, including trans ‐diaxial arrangement of the phosphoryl group and substituent in position 2 in trans ‐ 10 .…”

Synthetic strategies and diversification of dibenzo[1,5]diazocines

“…Next, the intramolecular cyclisation of C delivers a tricyclic intermediate D. Finally, the acylation of D with chloride substrate gives 52. 75 The reactivity of 2-aminobenzaldehyde for the formation of the trimeric skeleton containing a N-sulfonyl substituent has been investigated. In 2019, Dong et al 76 described the reaction of 2-aminobenzaldehyde with ethyl-(chlorosulfonyl)acetate in a mixture of pyridine and 1,2-dichloroethane which gave rise to the products 53 and 54 in 28 and 15% yields, respectively (Scheme 26).…”

“…The reaction afforded a major product, diethyl (2-formylphenyl)carbamoyl-methylphosphate in 49% yield as well as tricyclic 52 in a trace amount (Scheme 25). 75 In order to understand the formation of 52 , a tentative synthetic mechanism was proposed. Firstly, a self-condensation of 2-aminobenzaldehyde produces intermediate A , whereas intermediate B is formed from the reaction between the 2-aminobenzaldehyde and diethoxyphosphorylacetyl chloride substrates.…”