Synthetic Access Toward The Ginsenosides

The water extracts of the roots and leaves of Panax ginseng C. A. Meyer and its related plants have been used as effective tonics in traditional Chinese medicine for over2000years, in which the ginsenosides, mainly the glycosides of dammaranes, are considered as the major active principles. In fact, homogeneous ginsenosides have demonstrated a wide spectrum of pharmacological effects, including anticarcinogenic, immunostimulatory, antiatherosclerotic, antihypertensive, and antidiabetic effects, as well as effects on CNS and stress. On the other hand, ginsenosides occur in an extremely heterogeneous manner; over200such glycosides have thus far been identified from ginseng plants. Isolation of a homogeneous ginsenoside congener in an appreciable amount, especially for minor ginsenosides, is a difficult task. Chemical or enzymatic synthesis/transformation is another alternative to access to homogeneous ginsenosides, however, progress in this direction is also unsatisfactory. As a consequence, although a large number of ginsenoside derivatives have been identified in ginseng and related plants, most pharmacological studies on ginsenosides were done by using major saponins:ginsenosides Rbl, Rb2, Rc, and Rg. Nevertheless, many minor ginsenosieds such as ginsenoside Rhl, Rh2also possess promising bioactivities. Thus, it is highly desirable to devise an efficient approach to generate ginsenosides and their analogues. In line with our long efforts on the chemical synthesis of saponins and other glycoconjugates, we recently developed a highly efficient and mild glycosylation protocol with glycosyl ortho-alkynylbenzoates as donors and gold(I) complex as catalyst, which is especially advantageous in the glycosylation of acid labile aglycones. Benefited from the mild promotion conditions of ortho-alkynylbenzoate donors, we have achieved the highly efficient synthesis of protopanaxadiol type ginsenosides.