Construction Of Cortisol And C-KRN7000 By Heck-type Reaction

Despite attracting growing interest in biological and medicinal research, carbohydrates still have several limitations blocking their application as drugs, particularly among which is the liability of the glycosidic bond. In this context, C-glycosides seem to serve as possible surrogates. Moreover, C-glycosidic disaccharides are useful building blocks with attractive bio-activity. However, there have been only limited reports concerning the synthetic approaches to access C-glycosidic bonds between saccharide units. Therefore, a practical approach for the assembly of C-glycosidic disaccharides would be highly desirable.In this work, an effective Heck-type cross-coupling reaction between halo-exo-glycals and endo-glycals to achieve C-glycosidic disaccharides has been developed. Using Pd(OAc)2 as the catalyst, dppp as ligand and K2CO3 as base, the reactions gave C-glycosidic products in good to excellent yields with exclusive stereochemistry.Furthermore, we tried to reveal the power of the C-disaccharide strategy in the total synthesis of complex natural products. C-KRN7000, composed of a galactosylmoiety and a ceramide part, is an immunostimulant that has drawn extensive attention. The two moieties are connected by aa-C-glycosidic bond and the ceramide residue contains three chiral centers, rendering certain difficulties in the chemical synthesis. In this project, our aim is to construct the C-glycosidic bond using Suzuku-Miyaura reaction between two sugar building blocks, after which one sugar ring would be opened to provide the three chiral centers through a chiral pool strategy. Compared to existing synthetic routes, this method would bemore concise and avoided much asymmetric operation. At this stage, our major work is focused on the construction of the C-glycosidic disaccharide.