Cyanuric‐Chloride‐Mediated Synthesis of 2‐Aryl‐3‐tert‐butoxycarbonyl‐thiazolidine‐4‐carboxylic Acid Anilides: Mechanistic, X‐Ray Crystal Structures and Cytotoxicity Studies. Issue 43 (26th November 2019)

• Record Type: Journal Article
• Authors: Jagtap, Rohidas M.; Shaikh, Samir R.; Gonnade, Rajesh G.; Raheem, Shabnam; Rizvi, Masood A.; Pardeshi, Satish K.
• Is Part Of: ChemistrySelect. Volume 4:Issue 43(2019)
• Page Start: 12534
• Page End: 12546
• Publication Date: 2019-11-26
• Subjects: Cyanuric chloride -- Acid-amine coupling -- Mechanistic investigations -- Single crystal X-ray structure -- Cytotoxicity; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201903000
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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. Abstract : The cyanuric chloride mediated clean and ambient condition synthesis of '2R, 4R' ‐2‐aryl thiazolidine‐4‐carboxylic acid anilides via . diesterphenol intermediate is reported, and anilide formation is confirmed by single crystal X‐ray structures. The synthesized anilides are explored for their in vitro anti cancer, neuronal and neuroprotective studies.