Synthesis and bioactivity evaluation of 3‐hydroxy‐3‐(phenylethynyl)indol‐2‐one analogues

Abstract

A series of propargylic alcohol was synthesized by the addition of phenylacetylene to isatin and its N-substituted derivatives for the first time. This reaction involves activation of zinc reagent via coordination with carbonyl substrates that behave ''ligand like.'' The bioactivities on protective effect on the apoptosis of PC12 cells induced by H 2 O 2 and cytotoxicity against lung cancer A549 and P388 cell line of these compounds were investigated, and several compounds showed potent activities.

Crystal structure of 1-methyl-3-[((naphthalen-2-ylsulfonyl)oxy)imino]indolin-2-one, C19H14N2O4S

“…Some isatin (indoline-2,3-dione) derivatives attracted much attention and have extensive applications as sca old in medicinal chemistry related to their anti-bacterial, anti-virus and neuroprotection properties [2][3][4][5][6][7][8]. Some oxime derivatives have been also examined as useful pharmacophores in a range of therapeutic agents and considered as bioisosteres which provide a series of potent antiviral agents [9][10][11][12][13].…”

Copper/Guanidine‐Catalyzed Asymmetric Alkynylation of Isatins

“…Moreover,alkynes bearing branched and cyclic alkyl groups, or an alkene group,c ould be successfully utilized, thus forming the products 3cn-cr in 70-97 %yields and 93-96 % ee (entries [13][14][15][16][17][18]. The electronic properties and positions of the substituents on the phenyl group had aslight effect on the activity (3cb-ch).…”

“…[15] Fore xample,3 -alkynyl-3-hydroxyindolin-2-ones, analogues of efavirenz, show ab iological effect on Echinococcus multilocularis metacestodes. [17] Meanwhile,k etimines derived from isatins have been employed in copper(I)-catalyzed stereoselective alkynylations for the total synthesis of KAE609. [17] Meanwhile,k etimines derived from isatins have been employed in copper(I)-catalyzed stereoselective alkynylations for the total synthesis of KAE609.…”

Copper/Guanidine‐Catalyzed Asymmetric Alkynylation of Isatins

“…Areoptimization of the catalyst loading to 5mol %f or the reaction of 2-fluoro-, 4-fluoro-, 3-chloro-, and 3-methoxysubstituted phenylacetylene resulted in good yields and excellent enantioselectivities.W ith alkyl-substituted alkynes possessing functional groups,s uch as propionate,b enzoate, ether, or amine,t he corresponding products 3cj-cm were generated in 79-90 %y ields and 89-96 % ee (entries 9-12). Moreover,alkynes bearing branched and cyclic alkyl groups, or an alkene group,c ould be successfully utilized, thus forming the products 3cn-cr in 70-97 %yields and 93-96 % ee (entries [13][14][15][16][17][18]. With alkynes having longer substituted alkyl groups (2s-u), it was advantageous to use ahigher amount of catalyst to compensate for the reduction in reaction rate while maintaining high levels of enantiocontrol (78-89 %yield and 89-94 % ee,entries 19 and 20).…”

“…[16] Racemic derivatives have been synthesized through the addition of terminal alkynes to isatins by using either nBuLi, ZnEt 2 ,o rC uI/ DBU. [17] Meanwhile,k etimines derived from isatins have been employed in copper(I)-catalyzed stereoselective alkynylations for the total synthesis of KAE609. [18] Herein, we have developed an asymmetric version for enantioselective alkynylation of isatins to generate products useful for pharmacological evaluation.…”