Multicomponent Reactions for the Synthesis of Complex Piperidine Scaffoldsr多组分反应合成复杂哌啶骨架.pdfVIP

Angewandte Chemie DOI: 10.1002/anie.200806065 Synthetic Methods Multicomponent Reactions for the Synthesis of Complex Piperidine Scaffolds** Wei Zhu, Marisa Mena, Eric Jnoff, Na Sun, Patrick Pasau, and Lon Ghosez* The structures of small natural molecules have been opti- mized by evolution and are therefore tailored to interact with natural macromolecules to induce a biological response.[1] They represent an invaluable resource in the discovery process of new therapeutic agents. Since the natural product is usually not endowed with the biological properties desired for a chemotherapeutic agent, a series of skeletal and stereochemical analogues have to be generated by using synthesis. A promising strategy (diverted total synthesis, DTS)[1g] involves the production of a set of advanced intermediate scaffolds by using a multicomponent reaction (MCR)[2] and subsequent transformations to additionally Scheme 1. Sequence of five reactions leading to piperidone scaffolds. increase the molecular complexity and diversity. Polysubsti- TMS = trimethylsilyl, X = alkoxy, amide. tuted piperidines are common subunits in natural alkaloids and many biologically relevant molecules, representing attractive scaffolds for the production of natural product We envisioned the synthesis of the diene and the cyclo- analogues having interesting biological profiles. To the best of addition reac