L-Proline and related chiral heterocyclic amino acids as scaffolds for the synthesis of functionalized 2-amino-1,3-selenazole-5-carboxylates

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

“…The synthetic strategy for the synthesis of novel functionalized 1,2-oxazole derivatives is outlined in Scheme 1. The synthetic sequence began with preparing β-keto esters 2a-h by treating N-Boc-protected cyclic amino acids 1a-h with Meldrum's acid in the presence of EDC•HCl and DMAP, followed by methanolysis of the corresponding adducts [27,28,31,[36][37][38]. Reaction of the resulting β-keto esters 2a-h with N,N-dimethylformamide dimethylacetal afforded cycloaminyl β-enamino ketoesters 3a-h. After isolation of compounds 3a-h from the corresponding reaction mixtures, they were identified using LC-MS analysis, and were immediately treated with hydroxylamine hydrochloride in an appropriate solvent to obtain the target 1,2oxazoles 4a-h. A representative β-enamino ketoester 3a was subjected to a detailed NMR analysis (Figure 2a).…”

“…The synthetic strategy for the synthesis of novel functionalized 1,2-oxazole derivatives is outlined in Scheme 1 . The synthetic sequence began with preparing β-keto esters 2a – h by treating N -Boc-protected cyclic amino acids 1a – h with Meldrum’s acid in the presence of EDC·HCl and DMAP, followed by methanolysis of the corresponding adducts [ 27 – 28 31 , 36 – 38 ]. Reaction of the resulting β-keto esters 2a – h with N , N -dimethylformamide dimethylacetal afforded cycloaminyl β-enamino ketoesters 3a – h .…”

“…Recently, a highly specific and potent p38α kinase inhibitor containing a 3-amino-1-phenyl-1H-pyrazole-4-carboxylic acid residue was identified directly from the 12.6-million-member DNA-encoded small molecule library using yoctoReactor technology [26]. We have developed efficient protocols that provide easy access to highly functional heterocyclic compounds as novel amino acid-like building blocks by combining thiazole, selenazole, pyrazole, indazole, and indole moieties with both carboxyl functional groups and cycloaminyl units [27][28][29][30][31].…”

Methyl 2-Amino-4-[1-(tert-butoxycarbonyl)azetidin-3-yl]-1,3-selenazole-5-carboxylate

“…The multiplicity-edited 1 H- 13 C HSQC spectrum revealed a cross-peak correlating a methine proton at 4.67 ppm with the 13 C signal at 28.1 ppm from the azetidine ring (Figure 3). The aim of the present study was to extend our previous work on heterocyclic amino acids containing selenazole and azetidine cores [11][12][13][14], as it is still a new and potentially relevant field. In this work, a molecular system containing both selenazole and azetidine scaffolds was synthesized through Hantzsch cyclization of β-ketoester.…”

One-Pot Syntheses of Substituted 2-Aminothiazoles and 2-Aminoselenazoles via Meerwein Arylation of Alkyl Vinyl Ketones

“…Most 2-aminothiazole and 2-aminoselenazole derivatives are prepared by reactions of α-halocarbonyl compounds I with thioureas or selenoureas, 5 17 24 25 respectively (Scheme 1 ). A few approaches start from α-thiocyanato­ketones II , 26 isoselenocyanatoalkenes III , 27 or enamines IV .…”