Study On The Application Of Orthoesters In The Regioselection Protection Of Glucopyranoside And Efficient Preparation Of Ganglioside GM3 Trisaccharide

Oligosaccharides and glycoconjugates play important roles in biological processes. However, the complexity and microheterogeneity of the saccharides in biological tissues made it hard to meet the demand for significant amounts of these materials for advanced biological, medicinal, and pharmacological studies by extracting from nature resources. Therefore, new methods for the synthesis of glycosides are needed In this study, the application of orthoesters in the regioselection protection ofβ-D-glucopyranoside and efficient preparation of ganglioside GM3 trisaccharide by the glycosylation of N-phenyltrifluoroacetimidate donor with lactose-diol acceptor was reported.Study on the Application of Orthoesters in the Regioselection Protection of Glucopyranoside1 Three types of thioglycoside prepared from glucose were designed to reacted with methanol in the condition of NBS and TMSOTf to give orthoesters. Then a series of glucose derivatives with different protecting groups of 2,3 hydroxyls was afforded efficiently by protecting-group manipulation, orthoester hydrolysis and transesterification.2 Three factors were determined to contribute to the stabilization of the orthoester:the protecting group, the type and the configuration of the orthoesters.3 The absolute configuration of the chloromethylorthoesters diastereomers was determined by X-ray diffraction. While methylorthoester and phenylorthoester by NOESY. Those work laid great foundation for further mechanism elucidation. Efficient Preparation of Ganglioside GM3 Trisaccharide1 Glycosylation of lactose-diol acceptor 80 and sialic acid N-phenyltrifluoroacetimidate 71 was carried out to afford trisaccharide GM3 analogue 81 in a high yield of 70% and absolute a steroselectivity. Then, key intermediate 82 for the total synthesis of GM3 was obtained by acetylation of 81.2 An efficient procedure of the synthesis of trisaccharide unit of Ganglioside GM3 was explored.3 The mechanism of glycosylation catalyzed by TMSOTf or TBSOTf was preliminary studied, and the reactivity difference between the two catalyst was explained.