|
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).〔 〕〔 〕 The Holton Taxol total synthesis is a good example of a linear synthesis starting from commercially available natural compound patchoulene oxide.〔 〕 This epoxide can be obtained in two steps from the terpene patchoulol and also from borneol. 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 with an estimated 37 steps not counting the addition of the amide tail. One of the reasons is that the patchoulol starting compound 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. == Retrosynthesis == Holton's total synthesis of Taxol was derived from the natural product patchoulene oxide (1). The final stage of the synthesis was the formation of the tail by addition of the Ojima lactam 42 to alcohol 41. Of the four rings of Taxol, the D ring was formed last, the result of a simple intramolecular SN2 reaction of hydroxytosylate 33. Formation of the C ring took place through the Dieckmann condensation of ketone 20, with a Grignard reagent adding the final carbon for the ring system. Preparation for the C ring synthesis took place through a Chan rearrangement of carbonate ester 13 and subsequent oxidation and reduction reactions. The AB ring synthesis involved multiple rearrangements starting from epoxide 1 (patchoulene oxide). 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「Holton Taxol total synthesis」の詳細全文を読む スポンサード リンク
|