Paclitaxel Total Synthesis - Total Synthesis

Total Synthesis

The total synthesis of taxol is called one of the most hotly contested of the 1990s with around 30 competing research groups by 1992. The number of research groups actually having reported a total synthesis currently stands at 6 with the Holton group (article first accepted for publication) and the Nicolaou group (article first published) first and second in what is called a photo finish.

Some of the efforts are truly synthetic but in others a precursor molecule found in nature is included. The key data are collected below. What all strategies have in common is synthesis of the baccatin molecule followed by last stage addition of the tail, a process (except for one) based on the Ojima lactam.

1. Holton Taxol total synthesis - year: 1994 - precursor: Patchoulol - strategy: linear synthesis AB then C then D - references: see related article
2. Nicolaou Taxol total synthesis - year: 1994 - precursor: Mucic acid strategy: convergent synthesis A and C merge to ABC then D - references: see related article
3. Danishefsky Taxol total synthesis - year: 1996 - precursor: Wieland-Miescher ketone strategy: convergent synthesis C merges with D then with A merges to ABCD - references: See related article
4. Wender Taxol total synthesis - year: 1997 - precursor: Pinene strategy: linear synthesis AB then C then D - references:
5. Kuwajima Taxol total synthesis I. Kuwajima, - year: 1998 - precursor: synthetic building blocks strategy: linear synthesis A then B then C then D
6. Mukaiyama Taxol total synthesis T. Mukaiyama, - year: 1998 - Precursor: L-serine strategy: linear synthesis B, then C, then A then D. References: see related article.
7. Takahashi Taxol total synthesis T. Takahashi, - year: 2006 - Precursor: geraniol strategy: convergent synthesis A and C merge to ABC then D