Nicolaou Taxol total synthesis

Nicolaou Taxol total synthesis overview from raw material perspective.

The Nicolaou Taxol total synthesis, published by K. C. Nicolaou and his group in 1994 concerns the total synthesis of taxol.[1] Taxol 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.

This synthetic route to taxol is one of several; other groups have presented their own solutions, notably the group of Holton with a linear synthesis starting from borneol, the Samuel Danishefsky group starting from the Wieland-Miescher ketone and the Wender group from pinene.

The Nicolaou synthesis is an example of convergent synthesis because the molecule is assembled from three pre-assembled synthons. Two major parts are cyclohexene rings A and C that are connected by two short bridges creating an 8 membered ring in the middle (ring B). The third pre-assembled part is an amide tail. Ring D is an oxetane ring fused to ring C. Two key chemical transformations are the Shapiro reaction and the pinacol coupling reaction.[2] The overall synthesis was published in 1995 in a series of four papers.[3][4][5][6]

  1. ^ Classics in Total Synthesis: Targets, Strategies, Methods K. C. Nicolaou, E. J. Sorensen ISBN 3-527-29231-4
  2. ^ Nicolaou, KC; Yang, Z; Liu, JJ; Ueno, H; Nantermet, PG; Guy, RK; Claiborne, CF; Renaud, J; et al. (February 1994). "Total synthesis of taxol". Nature. 367 (6464): 630–4. Bibcode:1994Natur.367..630N. doi:10.1038/367630a0. PMID 7906395.
  3. ^ K. C. Nicolaou; P. G. Nantermet; H. Ueno; R. K. Guy; E. A. Couladouros & E. J. Sorensen (1995). "Total Synthesis of Taxol. 1. Retrosynthesis, Degradation, and Reconstitution". J. Am. Chem. Soc. 117 (2): 624–633. doi:10.1021/ja00107a006. S2CID 30357150.
  4. ^ K. C. Nicolaou; J.-J. Liu; Z. Yang; H. Ueno; E. J. Sorensen; C. F. Claiborne; R. K. Guy; C.-K. Hwang; M. Nakada & P. G. Nantermet (1995). "Total Synthesis of taxol. 2. Construction of A and C ring intermediates and initial attempts to construct the ABC ring system". J. Am. Chem. Soc. 117 (2): 634–644. doi:10.1021/ja00107a007.
  5. ^ K. C. Nicolaou; Z. Yang; J.-J. Liu; P. G. Nantermet; C. F. Claiborne; J. Renaud; R. K. Guy & K. Shibayama (1995). "Total Synthesis of Taxol. 3. Formation of Taxol's ABC Ring Skeleton". J. Am. Chem. Soc. 117 (2): 645–652. doi:10.1021/ja00107a008.
  6. ^ K. C. Nicolaou; H. Ueno; J.-J. Liu; P. G. Nantermet; Z. Yang; J. Renaud; K. Paulvannan & R. Chadha (1995). "Total Synthesis of Taxol. 4. The Final Stages and Completion of the Synthesis". J. Am. Chem. Soc. 117 (2): 653–659. doi:10.1021/ja00107a009.