Development of solid-phase methodology for the synthesis of combinatorial library

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Combinatorial chemistry has been shown to be an important tool that aids in the discovery of new drug leads as well as in the optimization of lead compounds. For a rapid assembly of a huge number of compounds, solid-phase methodology is very useful because it can simplify work up and purification. The methodology allows an automated synthesis of peptides and oligonucleotides. However application of the methodology to the synthesis of other bioactive molecules such as oligosaccharides and terpenes is exploring. Herein we describe the solid-phase synthesis of Vitamin D_3 and oligosaccharides.In Vitamin D_3 section we accomplished to synthesize 11-hydroxyl activated Vitamin D_3 derivatives by sequential coupling of a immobilized CD ring with A ring and side-chain moieties by Wittig reaction and cupper-mediated coupling reaction Combinatorial library synthesis using two A rings and six side-chains provided twelve Vitamin D_3 derivatives in good yields.In oligosaccharide section we first ac … More hieved the synthesis of branched pentasaccharides with _(1,3) linked tetrasacchraride backbone. Sequential coupling of glucoside moiety by glycosylation of solid-linked glycosyl accepter with mono- and di-sacchrides, followed by selective deprotection of Fmoc group gave a branched-pentasaccharide in moderate yield. Next, in order to synthesize oligosaccharides glycosylated with saccharides at various positions, we developed an orthogonal deprotectiong methodology on solid-phase. A tetraglucoside scaffold with three selective removable protecting groups at 6 position of a different glucose was prepared in liquid-phase. Selective deprotection of the scaffold on solid-phase, followed by glycosylation with a donor provided three different oligosaccharides with elicitor activity in rice cells. Finally solid-phase synthesis of di-branched heptasaccharide was conducted. The synthesis of a solid-linked scaffold with Fmoc and TBS groups through phenylsulfonate linker was achieved by orthogonal activation strategy using thioglycosides and glycosyl fluorides which involves no deprotection manipulation. Selective e deprotection of the two protecting group, followed by glycosylation afforded the heptasaccharide. Less