RESUMO
Protecting group-free synthesis of 1,2:5,6-di-anhydro-D-mannitol, followed by ring opening with propargylamine and subsequent ring closure produced a separable mix of piperidine N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and azepane N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol. In O-acetylated form, these two building blocks were subjected to CuAAC click chemistry with a panel of three differently azide-substituted glucose building blocks, producing iminosugar pseudo-disaccharides in good yield. The overall panel of eight compounds, plus 1-deoxynojirimycin (DNJ) as a benchmark, was evaluated as prospective inhibitors of almond ß-glucosidase, yeast α-glucosidase and barley ß-amylase. The iminosugar pseudo-disaccharides showed no inhibitory activity against almond ß-glucosidase, while the parent N-propargyl 1,5-dideoxy-1,5-imino-D-gulitol and N-propargyl 1,6-dideoxy-1,6-imino-D-mannitol likewise proved to be inactive against yeast α-glucosidase. Inhibitory activity could be reinstated in the former series by appropriate substitution on nitrogen. The greater activity of the piperidine could be rationalized based on docking studies. Further, potent inhibition of ß-amylase was observed with compounds from both the piperidine and azepane series.
Assuntos
Inibidores Enzimáticos/síntese química , Compostos Heterocíclicos com 1 Anel/síntese química , Imino Açúcares/síntese química , Piperidinas/síntese química , Triazóis/síntese química , alfa-Glucosidases/química , beta-Amilase/química , beta-Glucosidase/química , 1-Desoxinojirimicina/química , Azidas/química , Química Click/métodos , Dissacarídeos/química , Inibidores Enzimáticos/química , Glucose/química , Compostos Heterocíclicos com 1 Anel/química , Hordeum/química , Hordeum/enzimologia , Imino Açúcares/química , Manitol/química , Pargilina/análogos & derivados , Pargilina/química , Piperidinas/química , Propilaminas/química , Prunus dulcis/química , Prunus dulcis/enzimologia , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/enzimologia , Triazóis/química , beta-Amilase/antagonistas & inibidores , beta-Glucosidase/antagonistas & inibidoresRESUMO
A practical one-pot synthesis of nicotine analogs from Ugi 4-CR/propargyl adducts is reported. This methodology allows the rapid construction of the pyrrolidine moiety present in nicotine through an intramolecular base-promoted 5-endo cycloisomerization process, followed by a reduction of the resulting mixture of 2- and 3-pyrrolines to afford nicotine analogs in good overall yields.
Assuntos
Técnicas de Química Combinatória/métodos , Nicotina/análogos & derivados , Nicotina/síntese química , Catálise , Ciclização , Éteres de Hidroxibenzoatos/química , Estrutura Molecular , Nicotina/química , Oxirredução , Paládio/química , Pargilina/análogos & derivados , Pargilina/química , Propilaminas/química , Piridinas/química , EstereoisomerismoRESUMO
Herein, we describe an approach toward selenazole preparation based on the cycloisomerization of propargyl selenoamides. The selenoamides were synthesized in situ using the Ishihara reagent with spontaneous cyclization to form the 2,5-disubstituted selenazoles. Heterocylcles 9a-j were prepared using readily available starting materials, and yields ranged from moderate to good (20-80%). Methylselenazole 9a could be transformed into a bromomethyl derivative 13 using NBS. The intermediate 13 would provide a more versatile building block for further derivatizations, e.g., the cyanide 14.
Assuntos
Oxigênio/química , Pargilina/análogos & derivados , Pargilina/química , Compostos de Selênio/síntese química , Selênio/química , Catálise , Ciclização , Estrutura Molecular , Compostos de Selênio/químicaRESUMO
A series of 4-amino-7-chloroquinoline derivatives were synthesized by the reaction of 4,7-dichloro-quinoline with the corresponding diamine and then with propargyl bromide. In addition, platinum(II) complexes were obtained by reacting some of the organic derivatives with K(2)PtCl(4). Several of the synthesized compounds displayed antituberculosis activities. Compound 3 was 47.5 times more active than amphotericin B against Leishmania chagasi (IC(50)=0.04 µg/mL). Compounds 5, 6, 7, 9, 10, 11 and 13 presented promising results against Mycobacterium tuberculosis, with MIC values ranging from 12.5 to 15.6 µg/mL, comparable to the "first and second line" drugs used to treat tuberculosis.
Assuntos
Aminoquinolinas/síntese química , Aminoquinolinas/farmacologia , Antituberculosos/síntese química , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Leishmania/efeitos dos fármacos , Platina/química , Aminoquinolinas/química , Anfotericina B/farmacologia , Antituberculosos/química , Antituberculosos/farmacologia , Complexos de Coordenação/química , Diaminas/química , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Pargilina/análogos & derivados , Pargilina/químicaRESUMO
Long-chain polyacetylene alcohols, faulknerynes A-C, along with known compounds diplynes A, C and E, were isolated from two specimens of the encrusting sponge, Diplastrella sp., collected from the surface of coral in the Bahamas. Two CD methods were critically evaluated for their suitability to terminal propargylic glycols and applied to assignment of configurations of faulkneryne A and diplyne C.