RESUMO
Salacinol (4) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheses of salacinol (4), the enantiomer of salacinol (5), and a diastereomer (7) are described. The synthetic strategy relies on the selective nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D- or L-arabinitol at C-1 of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The work serves to resolve the ambiguity about the exact structure of salacinol and establishes conclusively the structure of the natural product.
Assuntos
Inibidores Enzimáticos/síntese química , Glicosídeo Hidrolases/antagonistas & inibidores , Álcoois Açúcares/síntese química , Sulfatos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Conformação Molecular , Extratos Vegetais/síntese química , Extratos Vegetais/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Álcoois Açúcares/química , Álcoois Açúcares/farmacologia , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/químicaRESUMO
The derivatives of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p-toluenesulfonates were synthesized and evaluated for antiallergic activity. The 2,3-dihydroxyethoxy group was introduced to the phenyl ring from the standpoint of lipophilicity and electronic effects of substituent. The IgE-induced rat passive cutaneous anaphylaxis (PCA) was inhibited by oral administration of several substituted 2-[(4-propoxyphenyl)carbamoyl]ethyldimethylsulfonium p-toluenesulfonate derivatives. Among them (+/-)-2-[N-[4-(3-ethoxy-2-hydroxypropoxy)phenyl]carbamoyl]ethyldimeth ylsulfonium p-toluenesulfonate (1a, IPD-1151T) was found to possess considerable activity in the PCA test, and it was launched as Suplatast tosilate in Japan.
Assuntos
Antialérgicos , Sulfonatos de Arila , Compostos de Sulfônio , Animais , Antialérgicos/síntese química , Antialérgicos/química , Antialérgicos/farmacologia , Sulfonatos de Arila/síntese química , Sulfonatos de Arila/química , Sulfonatos de Arila/farmacologia , Avaliação Pré-Clínica de Medicamentos , Imunoglobulina E/imunologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Anafilaxia Cutânea Passiva/imunologia , Ratos , Relação Estrutura-Atividade , Compostos de Sulfônio/síntese química , Compostos de Sulfônio/química , Compostos de Sulfônio/farmacologiaRESUMO
The use of single-column ion chromatography with conductometric detection was shown to be useful for the analysis of sulfonium and selenonium ions. A Hamilton PRP X-200 cation column was eluted with either solvent A (5 mM nitric acid in 30% methanol) or solvent B (4 mM nitric acid). With solvent B, trimethylsulfonium ion was separated from trimethylselenonium ion. With solvent A, amounts of trimethylsulfonium ion from 2 to 250 nmol were detected with a linear response. The retention times and response factors for a series of sulfonium ions with various organic groups were determined. In general the ions with more hydrophobic groups eluted later, but all had similar response factors. The method was shown to be useful for optimizing conditions for the synthesis of methylsulfonium ions, specifically the reaction of methyl iodide with diallyl sulfide.
Assuntos
Compostos Alílicos , Cromatografia por Troca Iônica/métodos , Compostos de Selênio , Selênio/análise , Compostos de Sulfônio/análise , Hidrocarbonetos Iodados , Sulfetos , Compostos de Sulfônio/síntese químicaRESUMO
Dopamine, at physiological pH, may exist as either an uncharged amine or a charged ammonium species. In order to gain insight as to which species is better suited for interaction with the dopamine receptor, we have synthesized dopamine analogues in which the nitrogen atom is replaced with a neutral methyl sulfide, a neutral methyl selenide, a charged dimethylsulfonium iodide, and a charged dimethylselenonium iodide. These analogues were tested for their ability to inhibit the K+-stimulated release of [3H]acetylcholine from striatal slices. At 30 microM concentration, the charged sulfonium and selenonium salts possessed significant agonist activity while the corresponding neutral species were inactive, suggesting that a charged species is optimal for dopamine agonist activity. In addition, the methyl sulfide was converted into the corresponding sulfoxide and sulfone; however, neither of these oxidation products possessed significant activity as dopaminergic agonists.