| As a representative of oleanane-type triterpenoid saponins,QS-21 has been drawing broad interest both from chemists and from pharmaceutists because of its powerful adjuvant activity.However,due to the complexity and instability,the chemical synthesis of QS-21 as well as its derivatives is extremely difficult.Great efforts from the Gin's group have led to the establishment of the first chemical approach for the synthesis of QS-21 and analogues thereof.Nevertheless,the existing synthetic route cannot be scaled up because of the difficult accessibility of the aglycone,the quillaic acid,which occurs in natural sources with extremely low content and accordingly is very expensive.In this thesis,with easily available protoaescigenin that can be obtained from the commercially available aescin as starting material,a reliable approach to generate quillaic acid was established featuring the conversions of hydrodesulfurization,samarium diiodide-mediated ?-deoxygenation,palladium-mediated reductive deoxygenation,and iridium-catalyzed C-H functionalization.The established synthetic route enjoys high flexibility,leading not only to quillaic acid but also to echicystic acid and acacic acid ?-lactone.In addition,the construction of the glycosidic linkage of 3-OH of quillaic acid in a highly efficient manner represents another challenge in the synthesis of QS-21 and its analogues because of low reactivity of the C3-OH resulted from the electron-withdrawing effect of the C23-carbonyl group.Thus,the other goal of our investigation is to set up a reliable protocol for the formation of such special glycosidic linkage.With glycosyl ortho-alkynylbenzotes as donors,a highly efficient protocol to construct the challenging glycosidic linkages of C3-OH of quillaic acid and its analogues has been disclosed under the promotion of catalytic amounts of Au(I)complex.Based on this,the synthesis of quillaic 3-O-trisaccharide saponin,the key intermediate of QS-21,was completed. |
PDF Full Text Request