Solid Phase Synthesis of (Benzannelated) Six-Membered Heterocycles via Cyclative Cleavage of Resin-Bound Pseudo-Oxazolones

Abstract

A solid supported procedure for the synthesis of benzoxazinones, dihydropyrazinones, quinoxalinones, and dihydrooxazinones using immobilized oxazolones in combination with difunctional nucleophiles as cleavage agent is presented. The scope of the novel method has been demonstrated through subsequent modification of the parent oxazolone scaffold on solid supports using conversions with electrophiles or CuAAC reactions to give functionalized pyrazin-2-ones. The described method allows the synthesis of the target heterocycles in good yields via three to five steps on solid phases with only one chromatographic purification step.

Chitosan: An Overview of Its Properties and Applications

“…D-p -HPG (or simply D-HPG, a D-amino acid) is a very useful chiral synthon, mainly used for the preparation of different semi-synthetic antibiotics, such as amoxicillin, cefadroxil, cefprozil, or cefoperazone [ 154 , 155 , 156 ] ( Figure 6 ), but also anticancer drugs [ 157 ] and some heterocyclic compounds [ 158 , 159 , 160 , 161 ].…”

“…Our group described the production of enantiopure D-p-hydroxyphenylglycine (D-p-HPG, Figure 6) using a multi-enzyme system containing D-hydantoinase and D-carbamoylase encapsulated in chitosan-based materials [150][151][152][153]. D-p-HPG (or simply D-HPG, a D-amino acid) is a very useful chiral synthon, mainly used for the preparation of different semi-synthetic antibiotics, such as amoxicillin, cefadroxil, cefprozil, or cefoperazone [154][155][156] (Figure 6), but also anticancer drugs [157] and some heterocyclic compounds [158][159][160][161].…”

“…3.5.2.2.] to transform D-p-hydroxyphenyl hydantoin (D-HPH) into Ncarbamoyl-D-p-hydroxyphenylglycine (C-p-HPG), which should be subsequently hydrolyzed by a second enzyme, a highly enantiospecific N-carbamoyl amino acid amidohy- D-p-HPG (or simply D-HPG, a D-amino acid) is a very useful chiral synthon, mainly used for the preparation of different semi-synthetic antibiotics, such as amoxicillin, cefadroxil, cefprozil, or cefoperazone [154][155][156] (Figure 6), but also anticancer drugs [157] and some heterocyclic compounds [158][159][160][161].…”

Chitosan: A Versatile Polymer for 21st Century

“…Schematic representation of the production of p-hydroxyphenylglycine (p-HPG) starting from a racemic mixture of p-hydroxyphenyl hydantoin (HPH) using a multi-enzyme system containing immobilized D-hydantoinase and D-carbamoylase. D-p-HPG (or simply D-HPG, a D-amino acid) is a very useful chiral synthon, mainly used for the preparation of different semi-synthetic antibiotics, such as amoxicillin, cefadroxil, cefprozil or cefoperazone [145][146][147] (Figure 6), but also anticancer drugs [148] and some heterocyclic compounds [149][150][151][152].…”

Copper-catalyzed direct coupling of benzoxazin-2-ones with indoles for the synthesis of diverse 3-indolylbenzoxazin-2-ones: access to natural cephalandole A

“…13,14 Owing to the importance of benzoxazin-2-ones, several methods for their synthesis have been reported. 15,16 The general methods for benzoxazin-2-ones include the domino reaction of o-aminophenol with b-nitroacrylates, 17 cleavage of resin-bound pseudooxazolones with 2-aminophenols, 18 and TFA-catalyzed tandem reaction of benzoxazoles with 2-oxo-2-arylacetic acids. 19 In addition, enantioselective hydrogenation of benzoxazinones and enantioselective addition of indoles to ketimines to give chiral dihydrobenzoxazinones have been accomplished.…”