|A team of Sweden-based chemists (DOI) have come up with a new way to add the tail in the cancer-curing drug Paclitaxel or Taxol (if you feel companies should not be allowed to hijack generic names as trade names). Although Taxol is a biomolecule that can be harvested from Taxus brevifolia, more of it is produced commercially from tail-less baccatin III that can be extracted from the more handy Taxus baccata. The tail is then added by reaction with the Ojima lactam (see Taxol total synthesis). |
The new method which appears less of a hassle than the Ojima method is based on an asymmetric Mannich reaction catalysed by (R)-proline. The aldehyde group is the oxidized to a carboxylic acid using Sodium chlorite and for some reason isobutene and KH2PO4 are thrown in as well. Esterfication to TES-protected baccatin III is accomplished with DMAP and DCP (di-2-pyridyl carbonate) and final deprotection with palladium on carbon and hydrochloric acid.