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Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol).〔Note that the original publications about the total synthesis use the name "taxol", which used to be the generic name before it was accepted as a trademark in 1992.〕 This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew (Taxus brevifolia). Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential. The paclitaxel molecule consists of a tetracyclic core called baccatin III and an amide tail. The core rings are conveniently called (from left to right) ring A (a cyclohexene), ring B (a cyclooctane), ring C (a cyclohexane) and ring D (an oxetane). The paclitaxel drug development process took over 40 years. The anti-tumor activity of a bark extract of the Pacific yew tree was discovered in 1963 as a follow up of a US government plant screening program already in existence 20 years before that. The active substance responsible for the anti-tumor activity was discovered in 1969 and structure elucidation was completed in 1971. Robert A. Holton of Florida State University succeeded in the total synthesis of paclitaxel in 1994, a project that he had started in 1982. In 1989 Holton had also developed a semisynthetic route to paclitaxel starting from 10-deacetylbaccatin III. This compound is a biosynthetic precursor and is found in larger quantities than paclitaxel itself in ''Taxus baccata'' (the European Yew). In 1990 Bristol-Myers Squibb bought a licence to the patent for this process which in the years to follow earned Florida State University and Holton (with a 40% take) over 200 million US dollars. == Total synthesis== The total synthesis of taxol is called one of the most hotly contested of the 1990s 〔''Creating complexity – the beauty and logic of synthesis'' Nina Hall Chem. Commun., 2003, 661 - 664, 〕 with around 30 competing research groups by 1992. The number of research groups actually having reported a total synthesis currently stands at 7 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. # Holton Taxol total synthesis - year: 1994 - precursor: Patchoulol - strategy: linear synthesis AB then C then D - references: see related article # Nicolaou Taxol total synthesis - year: 1994 - precursor: Mucic acid strategy: convergent synthesis A and C merge to ABC then D - references: see related article # 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 # Wender Taxol total synthesis - year: 1997 - precursor: Pinene strategy: linear synthesis AB then C then D - references:〔''The Pinene Path to Taxanes. 5. Stereocontrolled Synthesis of a Versatile Taxane Precursor'' Paul A. Wender et al.J. Am. Chem. Soc.; 1997; 119(11) pp 2755 - 2756; (Communication) 〕〔''The Pinene Path to Taxanes. 6. A Concise Stereocontrolled Synthesis of Taxol'' Wender, P. A. et al. J. Am. Chem. Soc.; (Communication); 1997; 119(11); 2757-2758. 〕 # Kuwajima Taxol total synthesis I. Kuwajima, - year: 1998 - precursor: synthetic building blocks strategy: linear synthesis A then B then C then D 〔''Enantioselective Total Synthesis of Taxol'' Koichiro Morihira, Ryoma Hara, Shigeru Kawahara, Toshiyuki Nishimori, Nobuhito Nakamura, Hiroyuki Kusama, and Isao Kuwajima J. Am. Chem. Soc.; (Communication); 1998; 120(49); 12980-12981. DOI (10.1021/ja9824932 )〕〔''Enantioselective Total Synthesis of (−)-Taxol'' Hiroyuki Kusama, Ryoma Hara, Shigeru Kawahara, Toshiyuki Nishimori, Hajime Kashima, Nobuhito Nakamura, Koichiro Morihira, and Isao Kuwajima. J. Am. Chem. Soc.; (Article); 2000; 122(16); 3811-3820. 〕 # Mukaiyama Taxol total synthesis T. Mukaiyama, - year: 1998 〔''New Method for the Synthesis of Baccatin III'' Isamu Shiina, Hayato Iwadare, Hiroki Sakoh, Masatoshi Hasegawa, Yu-ichirou Tani, and Teruaki Mukaiyama 1-2 1998 Chemistry Letters〕 - Precursor: L-serine strategy: linear synthesis B, then C, then A then D. References: see related article. # Takahashi Taxol total synthesis T. Takahashi, - year: 2006 〔''A Formal Total Synthesis of Taxol Aided by an Automated Synthesizer'' Takayuki Doi, Shinichiro Fuse, Shigeru Miyamoto, Kazuoki Nakai, Daisuke Sasuga and Takashi Takahashi Chemistry an Asian J.; (Article); 2006; 1(3); 370-383. DOI (Abstract )〕 - Precursor: geraniol strategy: convergent synthesis A and C merge to ABC then D Ongoing research efforts are directed at the synthesis of taxadiene and taxadienone intermediates. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Paclitaxel total synthesis」の詳細全文を読む スポンサード リンク
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