Synthesis And Antitumor Activity Of Diosgenin Analogs With Special Disaccharide Modules

Saponins have been found out owning a broad range of promising biological properties, such as antitumor and anti-inflammatory activities, and been considered as the key components in botanic medicines. However, further pharmacological studies towards saponins are often limited due to their lower contents in plant materials and the complicated isolation and purification work. As an important access to find novel sapogenyl glycoside structures, chemical synthesis plays a dominant role and receives increasing attention. Using the definite structures of some natural saponins for reference to guide the partial synthesis of diverse saponin compounds from a certain of cheap available sapogenins, followed with the pharmacological screenings of the synthetic compounds and summarizing the corresponding structures and activities relationships (SARs), is one of the effective researching strategies for saponin medicinal chemistry.The recent developments of the researches on the synthesis and structural modification of naturally active spirostanol saponins were summarized in the first chapter of the dissertation. It is quite clear that the activities of spirostanol saponins are related to both the aglycones and the sugar units. The diversity in structures of saponins lies mainly in their sugar moieties. Many studies have disclosed that some biological functions of spirostanol saponins can be most ascribed to the carbohydrate residue.Based on the relevant literature reported, we chose five monosaccharides and two disaccharides to synthesize the active sugar donors——glycosyl trichloroacetimidates and chose diosgenin as the aglycone. Therefore, 9 compounds (CW1-CW9) with similar trisaccharide moiety structures were prepared by stepwise glycosylation. Preliminary in vitro pharmacological research showed that compound CW1, CW2, CW3, and CW6 presented inhibition against cell SK-OV-3 under the 10μM. Therefore, it can be concluded that some trisaccharide moieties can induce the cytotoxicity of spirostanol steroidal glycosides, and the structures of sugar moieties play important roles in the activities.