555-29-3Relevant articles and documents
Multiple molecular targets mediated antioxidant activity, molecular docking, ADMET, QSAR and bioactivity studies of halo substituted urea derivatives of α-Methyl-L-DOPA
Anireddy, Jaya Shree,Avula, Vijaya Kumar Reddy,Chamarthi, Naga Raju,Mallepogu, Venkataswamy,Pasupuleti, Visweswara Rao,Ponne, Venkata Chalapathi,Vadabingi, Nagalakshmamma,Vallela, Swetha,Zyryanov, Grigory V.
, (2020/03/13)
A series of novel α-methyl-L-DOPA urea derivatives viz., 3-(3,4-dihydroxyphenyl)-2-methyl-2-(3-halo/trifluoromethyl substituted phenyl ureido)propanoic acids (6a-e) have been synthesized from the reaction of α-methyl-L-DOPA (3) with various aryl isocyanates (4a-e) by using triethylamine (5, TEA) as a base catalyst in THF at reflux conditions. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis studies and screened for their in-vitro antioxidant activity against DPPH, NO and H2O2 free radical scavenging assays and identified compounds 6c & 6d as potential antioxidants. The acquired in vitro results were correlated with the results of molecular docking, ADMET, QSAR and bioactivity studies performed for them and predicted that the recorded in silico binding affinities are in good correlation with the in vitro antioxidant activity results. The molecular docking analysis has comprehended the strong hydrogen bonding interactions of 6a-e with 1CB4, 1N8Q, 3MNG, 1OG5, 1DNU, 3NRZ, 2CDU, 1HD2 and 2HCK proteins of their respective SOD, LO, PRXS5, CP450, MP, XO, NO, PRY5 and HCK enzymes. This has sustained the effective binding of 6a-e and resulted in functional inhibition of selective aminoacid residues to be pronounced as multiple molecular targets mediated antioxidant potent compounds. In addition, the evaluated toxicology risks of 6a-e are identified with in the potential limits of drug candidates. The conformational analysis of 6c & 6d prominently infers that urea moiety uniting α-methyl-L-DOPA with halo substituted aryl units into a distinctive orientation to comply good structure-activity to inhibit the proliferation of reactive oxygen species in vivo.
Memory of chirality of tertiary aromatic amide: Application to the asymmetric synthesis of (S)-α-methylDOPA
Mai, Thi Thoa,Viswambharan, Baby,Gori, Didier,Kouklovsky, Cyrille,Alezra, Valerie
, p. 8797 - 8801,5 (2020/09/15)
We describe an original asymmetric synthesis of (S)-α-methylDOPA proceeding by the concept of memory of chirality, the only source of chirality being the starting d-alanine. The initial chirality of the amino acid is temporarily transferred to a dynamic axial chirality of a tertiary aromatic amide. The (S)-α-methylDOPA hydrochloride is obtained after four steps with 98% ee.
Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I
Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.
, p. 6354 - 6364 (2007/10/02)
Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.
