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

Abstract

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.

Keywords

• Asymmetric catalysis
• Multi-component reaction
• Green semi-synthesis
• Paclitaxel