A process for the reduction of oxiranyl epothilones to...

C - Chemistry – Metallurgy – 07 – D

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C07D 225/02 (2006.01) C07D 225/04 (2006.01) C07D 313/06 (2006.01) C07D 313/16 (2006.01) C07D 417/06 (2006.01)

Patent

CA 2375029

The invention as claimed is directed to a process for making an epothilone having structures (II) or (IV) from ones having an oxiranyl moiety, by reacting a compound having the latter structure with a metal or metal-assisted reagent. Said metal or metal-assisted reagent is selected from the group consisting of a) reactive metallocenes; b) [N2C(CO2Me)2, cat Rh2,(OAC)4]; c) [N2C(CO2Me)2, cat[(n-C7H15CO2)2 Rh]2]; d) [Zn-Cu, EtOH]; e) [Mg(Hg), MgBr]; f) Cr; g) [FeCl3, n-BuLi]; h) [TiCl3, LiAlH4]; i) [TiCl4, Zn]; j) [WCl6, LiAlH4]; k) [NbCl5, NaAlH4]; l) [VCl3,Zn] and m) [WCl6, n-BuLi].

Cette invention a trait à un procédé de production d'épothilone correspondant aux structures suivantes, (II) ou (IV), à partir d'ones portant une fraction oxiranyle, lequel procédé consiste à faire réagir un composé possédant la structure susmentionnée avec un métal ou un réactif assisté par un métal. Ce métal ou ce réactif assisté par un métal est choisi dans le groupe constitué par (a), des métallocènes réactifs ou (b), par [N¿2?C(CO¿2?Me)¿2?, cat Rh¿2?,(OAC)¿4?]; c), par [N¿2?C(CO¿2?Me)¿2?, cat[(n-C¿7?H¿15?CO¿2?)¿2? Rh]¿2?]; d), par [Zn-Cu, EtOH]; e), par [Mg(Hg), MgBr]; f), par Cr; g) [FeCl¿3?, n-BuLi]; h), par [TiCl¿3?, LiAlH¿4?]; i), par [TiCl¿4?, Zn]; j), par [WCl¿6?, LiAlH¿4?]; k), par [NbCl¿5?, NaAlH¿4?]; l), par [VCl¿3?,Zn] et m), par [WCl¿6?, n-BuLi].

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