10.1021/jo7018812
The research focuses on the total synthesis of OSW-1, a natural saponin with significant antitumor activities, which was synthesized from (+)-dehydroisoandrosterone, L-arabinose, and D-xylose on a gram scale. The study aimed to develop a new, efficient, and practical method for synthesizing OSW-1, a promising lead compound for the development of novel antitumor drugs, due to its potent cytotoxicity against various malignant tumor cells. The synthesis was achieved in 10 linear steps with an overall yield of 6.4%, starting from (+)-dehydroisoandrosterone. The research concluded that the developed synthetic strategy was reliable, with simple workup procedures, enabling large-scale synthesis and providing a foundation for the preparation of various OSW-1 derivatives for further studies on structure-activity relationships and potential anticancer therapeutics. Key chemicals used in the process included propanenitrile, 3-methylbutylmagnesium bromide, NaOH, TBS chloride, ethylene glycol, and a variety of other reagents and solvents employed in the multi-step synthesis procedure.
10.1021/tx950065t
The research investigates the quantitative relationships between substrate structure and the catalytic activity of sulfotransferase a (STa), an enzyme that catalyzes the formation of sulfuric acid esters from alcohols. The study aims to understand the specificity of STa for various alcohols, including both endogenous and xenobiotic compounds. Key chemicals involved in the research include benzyl alcohol and a series of benzylic alcohols substituted with n-alkyl groups (CnH2n+1, where n ranges from 1 to 8), primary n-alkanols (CnH2n+1OH, where n ranges from 3 to 16), and various other alcohols such as cholesterol, dehydroepiandrosterone (DHEA), and several phenols. The researchers also used 7-(hydroxymethyl)-12-methylbenz[a]anthracene (HMBA) to study the enzyme's activity with a carcinogenic compound. The study employed methods such as purification of STa, determination of kinetic constants (kcat/Km values), and molecular modeling to analyze the influence of substrate hydrophobicity and steric effects on the catalytic efficiency of STa. The findings revealed that hydrophobicity of the substrate is a major factor contributing to the catalytic efficiency, with optimal catalytic efficiency observed for certain chain lengths of aliphatic alcohols and benzylic alcohols. The study also highlighted limitations in substrate size and the importance of steric effects, providing insights into the enzyme's specificity for different alcohols.
10.1007/s00044-012-0059-1
The study investigates the creation and evaluation of imidazolyl substituted 16E-arylidenosteroidal derivatives for their potential as aromatase inhibitors, which are crucial in treating estrogen-dependent tumors such as breast cancer. The researchers synthesized various steroidal hybrids by condensing imidazole with the androstane nucleus. Key chemicals involved include dehydroepiandrosterone (DHA), substituted benzaldehydes, and imidazole. The synthesis process involved aldol condensation of DHA with substituted benzaldehydes to form 16-benzylidene steroidal derivatives, which were then fused with imidazole and subjected to Oppenauer oxidation to yield the final products. The most potent compound, 16-[3-{3-(imidazol-1-yl)propoxy}benzylidene]-4-androstene-3,17-dione (10), exhibited an IC50 value of 4.4 μM, making it seven times more potent than the standard drug aminoglutethimide. The study highlights the significance of structural modifications in enhancing the binding affinity of these steroidal derivatives with the aromatase enzyme, with meta-substituted compounds showing more promise than para-substituted ones.
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