A very short and efficient synthesis of the important drug candidate telaprevir, featuring a biocatalytic desymmetrization and two multicomponent reactions as the key steps, is presented. The classical issue of lack of stereoselectivity in Ugi- and Passerini-type reactions is circumvented. The atom economic and convergent nature of the synthetic strategy require only very limited use of protective groups.
Time and pep‐tide wait for no man: Optically pure 3,4‐disubstituted 1‐pyrrolines, generated from the corresponding meso‐pyrrolidines by biocatalytic desymmetrization (MAO‐N=monoamine oxidase N), react with carboxylic acids and isocyanides in a highly diastereoselective Ugi‐type multicomponent reaction to give substituted prolyl peptides of high pharmaceutical relevance.
We have combined the biocatalytic desymmetrization of 3,4-cis-substituted meso-pyrrolidines with an Ugi-type multicomponent reaction followed in situ by a Pictet-Spengler-type cyclization reaction sequence for the rapid asymmetric synthesis of alkaloid-like polycyclic compounds.
Palladium-catalyzed cross-coupling of a wide range of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion followed by lactamization efficiently affords 4-aminophthalazin-1(2H)-ones that are difficult to obtain regioselectively by classical methods.
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