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Cyanuric‐Chloride‐Mediated Synthesis of 2‐Aryl‐3‐tert‐butoxycarbonyl‐thiazolidine‐4‐carboxylic Acid Anilides: Mechanistic, X‐Ray Crystal Structures and Cytotoxicity Studies
Author(s) -
Jagtap Rohidas M.,
Shaikh Samir R.,
Gonnade Rajesh G.,
Raheem Shabnam,
Rizvi Masood A.,
Pardeshi Satish K.
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201903000
Subject(s) - thiazolidine , chemistry , aryl , carboxylic acid , carboxylate , amine gas treating , stereochemistry , organic chemistry , alkyl
The ‘2R,4R’ ‐2‐aryl thiazolidine‐4‐carboxylic acid anilides ( ATCAAs ) were synthesized using cyanuric chloride ( CC) as a clean and substoichiometric acid‐amine coupling agent under optimized reaction conditions. The diesterphenol intermediate based mechanism is proposed and supported by spectral characterization of the intermediate. The single crystal X‐ray structures of acid substrate ( 2R,4R )‐3‐( tert ‐butoxycarbonyl)‐2‐(2‐methoxyphenyl)thiazolidine‐4‐carboxylic acid (3 a) and anilides ( R )‐ tert ‐butyl 4‐(2‐fluorophenylcarbamoyl)thiazolidine‐3‐carboxylate ( 4 b) , ( 2R,4R )‐ tert ‐butyl 2‐(2,6‐dichlorophenyl)‐4‐( m ‐tolylcarbamoyl)thiazolidine‐3‐carboxylate (6 b) confirmed the formation of chiral anilides. The synthesized library of anilides [( R )‐ tert ‐butyl 4‐Aryl thiazolidine‐3‐carboxylate and ( 2R,4R )‐ tert ‐butyl 2‐Aryl‐4‐Aryl thiazolidine‐3‐carboxylate] 4 a‐6 f was screened for their in vitro anti cancer, neuronal and neuroprotective studies. The anilides 4 b, 4 g, 5 d, 5 h, 6 c and 6 f (where the aryl=2‐fluorophenylcarbamoyl, 4‐chlorophenylcarbamoyl, 2‐methoxyphenyl, 2,5‐dichlorophenylcarbamoyl, 2,6‐dichlorophenyl, 4‐chlorophenylcarbamoyl respectively)were found to be less cytotoxic towards N2 A, SHSY‐5Y neuronal cell lines in their differentiated and undifferentiated forms, and also exhibited dose dependant anti‐inflammatory properties for a possible identification towards neurodegenerative and inflammatory disorders.