Holton Taxol total synthesis overview from raw material perspective
The Holton Taxol total synthesis, published by Robert A. Holton and his group at Florida State University in 1994, was the first total synthesis of Taxol (generic name: paclitaxel).[1][2]
The Holton Taxol total synthesis is a good example of a linear synthesis. The synthesis starts from patchoulene oxide, a commercially available natural compound .[3]
This epoxide can be obtained in two steps from the terpene patchoulol and also from borneol.[4][5] The reaction sequence is also enantioselective, synthesizing (+)-Taxol from (−)-patchoulene oxide or (−)-Taxol from (−)-borneol with a reported specific rotation of +- 47° (c=0.19 / MeOH). The Holton sequence to Taxol is relatively short compared to that of the other groups (46 linear steps from patchoulene oxide). One of the reasons is that patchoulene oxide already contains 15 of the 20 carbon atoms required for the Taxol ABCD ring framework.
Other raw materials required for this synthesis include 4-pentenal, m-chloroperoxybenzoic acid, methyl magnesium bromide and phosgene. Two key chemical transformations in this sequence are a Chan rearrangement and a sulfonyloxaziridine enolate oxidation.
^Robert A. Holton; Carmen Somoza; Hyeong Baik Kim; Feng Liang; Ronald J. Biediger; P. Douglas Boatman; Mitsuru Shindo; Chase C. Smith; Soekchan Kim; Hossain Nadizadeh; Yukio Suzuki; Chunlin Tao; Phong Vu; Suhan Tang; Pingsheng Zhang; Krishna K. Murthi; Lisa N. Gentile; Jyanwei H. Liu (1994). "First total synthesis of taxol. 1. Functionalization of the B ring". J. Am. Chem. Soc. 116 (4): 1597–1598. doi:10.1021/ja00083a066.
^Robert A. Holton; Hyeong-Baik Kim; Carmen Somoza; Feng Liang; Ronald J. Biediger; P. Douglas Boatman; Mitsuru Shindo; Chase C. Smith; Soekchan Kim; Hossain Nadizadeh; Yukio Suzuki; Chunlin Tao; Phong Vu; Suhan Tang; Pingsheng Zhang; Krishna K. Murthi; Lisa N. Gentile; Jyanwei H. Liu (1994). "First Total Synthesis of Taxol. 2. Completion of the C and D Rings". J. Am. Chem. Soc. 116 (4): 1599–1600. doi:10.1021/ja00083a067.
^Robert A. Holton; R. R. Juo; Hyeong B. Kim; Andrew D. Williams; Shinya. Harusawa; Richard E. Lowenthal; Sadamu. Yogai (1988). "A synthesis of taxusin". J. Am. Chem. Soc. 110 (19): 6558–6560. doi:10.1021/ja00227a043.
^Buchi, G.; MacLeod, William D.; Padilla, J. (1964-10-01). "Terpenes. XIX.1 Synthesis of Patchouli Alcohol2". Journal of the American Chemical Society. 86 (20): 4438–4444. doi:10.1021/ja01074a041. ISSN 0002-7863.
^Büchi, G.; Erickson, R. E.; Wakabayashi, Nobel (1961-02-01). "Terpenes. XVI.1,2 Constitution of Patchouli Alcohol and Absolute Configuration of Cedrene". Journal of the American Chemical Society. 83 (4): 927–938. doi:10.1021/ja01465a042. ISSN 0002-7863.
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