1. Synthesis of 2-Alkylsulfonyl-imidazoles with Three Diversity Positions from Immobilized α-Acylamino Ketones
Petra Králová, Miroslav Soural ACS Comb Sci. 2018 Aug 13;20(8):467-471. doi: 10.1021/acscombsci.8b00075. Epub 2018 Jul 10.
The synthesis of novel imidazole derivatives via immobilized α-acylamino ketones is reported in this article. The key intermediates were prepared from the Wang-piperazine resin-supported Fmoc-amino acids. After their sulfonylation with 4-nitrobenzenesulfonyl chloride (4-Nos-Cl), followed by alkylation with α-bromoketones and cleavage of Nos group, the resulting α-acylamino ketones were reacted with Fmoc-isothiocyanate. The corresponding Fmoc-thioureas were subjected to the Fmoc-cleavage and spontaneous ring-closure to imidazole scaffold. The resulting imidazole-thiones were alkylated with alkyl halides and oxidized using meta-chloroperbenzoic acid ( mCPBA). Trifluoroacetic acid (TFA)-mediated cleavage yielded the corresponding trisubstituted 2-alkylsulfonyl imidazoles in good crude purity and acceptable overall yields. In the case of sulfides, prepared from alkyl bromides, the unexpected products brominated at the C4 position of the imidazole were obtained.
2. Combinatorial synthesis of oxazol-thiazole bis-heterocyclic compounds
Siva Murru, Adel Nefzi ACS Comb Sci. 2014 Jan 13;16(1):39-45. doi: 10.1021/co400133a. Epub 2013 Dec 9.
A combinatorial library of novel oxazol-thiazole bis-heterocycles was synthesized in good to excellent overall yields with high purity using a solution and solid-phase parallel synthesis approach. Oxazole amino acids, prepared from serine methyl ester and amino acids via coupling and cyclodehydration, were treated with Fmoc-NCS and α-haloketones for the parallel synthesis of diverse bis-heterocycles. Fmoc-isothiocyanate is used as a traceless reagent for thiazole formation. Oxazole diversity can be achieved by using variety of amino acids, whereas thiazole diversity is produced with various haloketones.
3. Convenient Synthesis of Thiohydantoins, Imidazole-2-thiones and Imidazo[2,1- b]thiazol-4-iums from Polymer-Supported α-Acylamino Ketones
Petra Králová, Michal Maloň, Hiroyuki Koshino, Miroslav Soural Molecules. 2018 Apr 23;23(4):976. doi: 10.3390/molecules23040976.
The preparation of 5-methylene-thiohydantoins using solid-phase synthesis is reported in this paper. After sulfonylation of immobilized Ser (t-Bu)-OH with 4-nitrobenzenesulfonyl chloride followed by alkylation with various bromoketones, the 4-Nos group was removed and the resulting polymer-supported α-acylamino ketones reacted with Fmoc-isothiocyanate. Cleavage of the Fmoc protecting group was followed by the spontaneous cyclative cleavage releasing the 5-methylene-thiohydantoin derivatives from the polymer support. Reduction with triethylsilane (TES) yielded the corresponding 5-methyl-thiohydantoins. When Fmoc-isothiocyanate was replaced with alkyl isothiocyanates, the trifluoroacetic acid (TFA) mediated cleavage from the polymer support, which was followed by the cyclization reaction and the imidazo[2,1-b]thiazol-4-iums were obtained. Their conversion in deuterated dimethylsulfoxide led to imidazole-2-thiones.
