Synthesis of Bioactive Diosgenyl Saponins and Their 2D NMR Analysis

Saponins, complex glycosides of steroids or triterpenes, are wide distributed in plants and possess significant pharmacological activities. Many chinese traditional herbs contain saponins as the major biologically active ingredients. It is very difficult to study the pharmacological mechanism of the actions of saponins due to the lack of stable and large acquisition of the pure single saponins from natural sources. Chemical synthesis of saponins would pave a way to this demand. Therefore, it is of great significance to synthesize those biologically active saponins, either naturally occurring saponins

1. Synthesis of bioactive diosgenyl saponins with 2,4-branched saccharides.
    Saponins 1 and 2 are structurally typical diosgenyl saponins with 2,4-branched saccharide, which have been isolated from medical plants. The common building block of them was synthesized by glycosylation of diosgenin with a protected glucose bromide, followed by protecting group manipulation and glycosylation. The final protected saponins were synthesized successfully in either a "one-pot" or a stepwise manner by use of the glycosyl trichloroacetimidate and thioglycosides. Removal of protecting groups gave the two tetrasaccharide saponins.
2. Synthesis of bioactive diosgenyl saponins with linear saccharides.
    Saponins 3-6 are structurally typical diosgenyl saponins with linear saccharides. The glucose residue was coupled to diogenin, after deprotection and protection, provided the common building block with the 4-OH on Glc free. With the combined use of glycosyl trichloroacetimidates and thioglycosides, the final protected saponins were efficiently synthesized, in either a "one-pot" or a stepwise manner. Removal of protecting groups gave the four diosgenyl saponins (3-6).
In the synthesis of disaccharide donor, trichloroacetimidate was used as a novel protective group whereas the anomeric trichloroacetimidate at the same time was employed as a leaving group.
3. Studies of an efficient protective group for alcohols.Trichloro-acetimidate
    Although the trichloroacetimidate has widely been used in organic chemistry, few reports mentioned its use as a temporary protective group. In this part of the thesis, the trichloroacetimidate was developed as an efficient protective group for alcohols. The trichloroacetimidate is disclosed to be a general and efficient protective group for alcohols, which can be deprotected under mild acidic, basic, or neutral conditions, and has orthogonal stability with both acetate and TBS protection.
4. NMR analysis of the synthesized saponins
    In this part of the thesis, the complete assignments of ¹H and ¹³C NMR signal for the six synthesized diosgenyl saponins are accomplished by ¹H-¹H COSY, TOCSY, HSQC, HMBC, and ROESY spectra. The changes of ¹³C chemical shifts for various saponins are discussed.