A short de novo synthesis of nucleoside analogs

We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of D- or L-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2 ′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.
Source: Organometallic Current - Category: Chemistry Tags: Nucleosides Source Type: blogs