The Nicolaou Taxol total synthesis, published by K. C. Nicolaou and his group in 1994 concerns the total synthesis of taxol. 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.
The overall synthesis was published in 1995 in a series of four papers.
As illustrated in Retrosynthetic Scheme I, Taxol was derived from diol 7.2 by an ester bond formation, according to the Ojima-Holton method. This diol comes from carbonate 6.3 by the addition of phenyllithium. The oxetane ring in compound 6.3 was obtained via an SN2 reaction involving a mesylate derived from acetal 4.9. Ring B was closed via a McMurry reaction involving dialdehyde 4.8 which ultimately was derived from aldehyde 4.2 and hydrazone 3.6 using a Shapiro coupling reaction.
Retrosynthetic Scheme II indicates that both the aldehyde and the hydrazone used in the Shapiro coupling reaction were synthesized using Diels-Alder reactions.
As shown in Scheme 1, the ring synthesis of ring C began with a Diels-Alder reaction between diene 1.3 and dienophile 1.1 in the presence of phenylboronic acid (1.2), which, after addition of 2,2-dimethyl-1,3-propanediol, gave five-membered lactone 1.8 in 62% yield.
Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.
La première partie du cours décrit les méthodes classiques de synthèse asymétrique. La seconde partie du cours traite des stratégies de rétrosynthèse basées sur l'approche par disconnection.
Complex polycyclic natural products are chosen to illustrate the evolution of the state-of-the-art of the field, the interplay between strategy and new reactions as well as the importance of implement
The Danishefsky Taxol total synthesis in organic chemistry is an important third Taxol synthesis published by the group of Samuel Danishefsky in 1996 two years after the first two efforts described in the Holton Taxol total synthesis and the Nicolaou Taxol total synthesis. Combined they provide a good insight in the application of organic chemistry in total synthesis. Danishefsky's route to Taxol has many similarities with that of Nicolaou. Both are examples of convergent synthesis with a coupling of the A and the C ring from two precursors.
Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). 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.
Wender Taxol total synthesis in organic chemistry describes a Taxol total synthesis (one of six to date) by the group of Paul Wender at Stanford University published in 1997. This synthesis has much in common with the Holton Taxol total synthesis in that it is a linear synthesis starting from a naturally occurring compound with ring construction in the order A,B,C,D. The Wender effort is shorter by approximately 10 steps. Raw materials for the preparation of Taxol by this route include verbenone, prenyl bromine, allyl bromide, propiolic acid, Gilman reagent, and Eschenmoser's salt.
Explore la synthèse totale des produits naturels, les stratégies, l'impact sur la science et la société, le développement de médicaments et les études biologiques.
Couvre la synthèse totale de Discodermolide, un puissant composé immunosuppresseur et cytotoxique.
The first chapter of this thesis describe the development of a general synthesis of ynimines, an under-exploited motif in organic chemistry. In the presence of an inexpensive copper catalyst and 2,2'-biquinoline, reaction of easily accessible O-acyloximes ...
Selective synthesis of nanocluster (NC) isomers with tailored structures holds significant importance for enhancing their applications. Here, we develop an effective strategy for the selective synthesis of CdS NC isomers through the judicious choice of a p ...
Metal-organic frameworks (MOFs) have firmly established in the field of porous materials since their early discovery in the 1990s. With a plethora of applications, these materials offer endless possibilities owing to their tunable, modular nature. The vast ...