An asymmetric catalytic multi-component reaction enabled the green synthesis of isoserine derivatives and semi-synthesis of paclitaxel

Paclitaxel(Taxol^(@))as a cornerstone of chemotherapy remains in high demand.The semi-synthesis of paclitaxel via coupling of Taxus leaf-produced baccatin III and manually synthesized isoserine(C-13 side chain)is one of the solutions to avoid environmental damage caused by the sacrifice of the whole Taxus brevifolia.A green synthesis of the C-13 side chain is pivotal to the green production of paclitaxel.We herein report a green synthesis of isoserine derivatives and the semi-synthesis of paclitaxel via a straightforward assembly of isoserines based on an Rh2(TPA)3(OAc)/CPA1 co-catalyzed asymmetric multi-component reaction of ethyl diazoacetate,triethyl silanol and N-(anthrancen-9-ylmethyl)benzaldimine.The method is featured by improved atom economy,effective mass yield,and environmental factors compared to our previous racemic method and BMS company's semi-synthesis method.And the method allows for rapid access to paclitaxel derivatives with varied C-13 side chains.

A sustainable synthesis of 3,3-disubstituted oxindoles via CuBr-catalysed capture of carboxylic oxonium ylides with isatylidene malononitrile

We herein reported a sustainable synthesis of 3,3-disubstituted oxindoles via a Michael-type reaction based on the CuBr-catalysed capture of carboxylic oxonium ylides with isatylidene malononitrile.The reaction is characterized by a high atom economy and low economic constraints.The catalyst CuBr could be conveniently recyclized.The products of the reaction were found to be inhibitory against Na ion channels.We expect the reaction to shed the light on synthesis of biologically interesting molecules directed by principles of green chemistry.