A Formal Total Synthesis of Taxol Aided by an Automated Synthesizer

Abstract

A 36-step synthesis was carried out in automated synthesizers to provide a synthetic key intermediate of taxol. A key step involved a microwave-assisted alkylation reaction to construct the ABC ring system from an AC precursor. Subsequent formation of the D ring afforded baccatin III, a well-known precursor of taxol.

Synthesis of Paclitaxel. 1. Synthesis of the ABC Ring of Paclitaxel by SmI2-Mediated Cyclization

“…12 Thus, treatment of hydrazone 5, synthesized from 1,3-cyclohexanedione in six steps, 24 with BuLi afforded a vinyl anion species, which was then reacted with C-ring 6 (Scheme 2). The reaction proceeded under chelation control 6c to produce 13 in 92% yield as a single isomer.…”

Development and Application of a Solution-Phase Automated Synthesizer, 'ChemKonzert'

“…In fact, efficient preparations of key intermediates for syntheses of TAXOL ® and the 9-membered masked enediyne have recently been achieved by using ChemKonzert. 10,11) It is indicated that the automated synthesizer can be utilized in broad area of organic syntheses.…”

Oxetanes as versatile building blocks in the total synthesis of natural products: An overview

“…To date, seven methods was used in description the total synthesis of taxol [94][95][96][97][98][99][100][101][102][103]. Nicolaou and his co-workers were reported total synthesis of taxol and in 1994 [104][105][106][107].…”