Application of the Dakin−West Reaction for the Synthesis of Oxazole-Containing Dual PPARα/γ Agonists

Abstract

An improved method for the preparation of a series of oxazole-containing dual PPARalpha/gamma agonists is described. A synthetic sequence utilizing a Dakin-West reaction was devised that allows for the introduction of the oxazole ring either late in the synthetic sequence via aminomalonate-derived chemistry or in pivotal SAR intermediates derived from aspartic acid.

Silica Supported Tungstosilicic Acid as an Efficient and Reusable Catalyst for the One-Pot Synthesis of β-Acetamido Ketones via a Four-Component Condensation Reaction

“…[13][14][15] These supported catalysts have been widely studied and found useful in many reactions such as the synthesis of 2,4-dihydropyrimidones, 16 metanethole, 17 α-aminonitriles 18 and esterification. 19,20 The β-acetamido carbonyl compounds, in that their skeletons exist in a number of valuable biologically or pharmacologically active compounds, 21,22 has gained considerable attention in organic synthesis, owing to their importance as versatile intermediates for preparation of β-amino acids, 23 or 1,3-amino alcohols 24 as well as for the synthesis of various antibiotics such as nikkomycins or neopolyoxines 25 and potent molecules in α-glucosidase inhibitory activity. 26 β-Acetamido ketones were usually prepared through Michael addition to α,β-unsaturated ketones, 27 acylation of β-aminoketones, 28 or photoisomerisation of phthalimides.…”

NaHSO4•H2O as an efficient and eco-friendly catalyst for the one-pot multicomponent synthesis of β-acetamido ketones under mild and heterogeneous conditions

“…Thus, MCRs have attracted considerable interest owing to their exceptional synthetic efficiency. 4 Acetamido-or amino-ketone derivatives are important for their biological and pharmaceutical properties, 5,6 and in the preparation of antibiotic drugs such as nikkomycine or neopolyoxines. 7,8 The best known route for the synthesis of this class of compounds is the Dakin-West reaction, 9 the condensation of an α-amino acid with acetic anhydride in the presence of a base provides the α-acetamido ketones via an azalactone intermediate.…”

One-pot preparation of β–amido ketones and esters in four-component condensation reaction using ferric hydrogensulfate as effective and reusable catalyst

“…[1][2][3][4][5][6][7][8] Amido-or amino ketone derivatives are important for their biological, pharmaceutical properties, 9,10 and in the preparation of antibiotic drugs such as nikomycine or neopolyoxines. 11,12 The common procedure for the synthesis of these class compounds is the Dakin-West reaction [13][14][15] which involves the condensation of α-amino acids with acetic anhydride in the presence of suitable base, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] these reaction produce α-acetamido ketones ZnO, 29 Amberlyst-15, 30 iodine 31 and FeCl 3 .6H 2 O. 32 Ferric salts have applied for the formation of carbon-nitrogen and carbon-oxygen bonds in organic synthesis.…”