Strategi Sintesis Total Senyawa Epotilon: Suatu Senyawa Aktif Baru Yang Potensial Sebagai Anti-Kanker

Abstract

ABSTRAK

Epotilon adalah suatu makrosiklik lakton kelas baru yang menarik oleh karena daya aktivitasnya sebagai zat anti kanker. Senyawa makrolida ini diisolasi pertama kali oleh  kelompok Höfle dari Myxobacterium Sorangium cellulosum strain 90 yang diambil dari Sungai Zambezi Afrika Selatan. Berbagai uji biokimia mengunkapkan bahwa epotilon lebih potensial dibandingkan taksol dengan efek samping lebih kecil.   Setelah konfigurasi absolut epotilon A (I) dan B (2) dipublikasikan oleh Höfle, dan kawan-kawan, total sintesis epotilon dan turunanya secara intensif telah dilakukan. Publikasi pertama sintetis epotilon total oleh  Danishefsky dan kawan-kawan, diikuti oleh Nicolou dan kawan-kawan,  dan Shinzer dan kawan-kawan. Meskipun masing-masing kelompok mempunyai strategi tersendiri, ketiga kelompok tersebut menggunakan reaksi-reaksi olefin-metatesis, makrolaktonisasi, dan aldol sebagai reaksi-reaksi penyambung.

Key words: Epothilone, totalsynthesis, olefin-Metatesis, macrolactonisation, aldol reaction

ABSRACT

Epothilone is a new class of macrocyclic lactones, which has drawn because of its powerful activity as anticancer agent. This macrolide compound was first isolated by Höfle’s group from the myxobacterium Sorangium cellulosum strain 90 that were harvested off the shores of the Zambezi River in South Africa. In various biochemical assays have revealed that the epothilones are more potent than taxol with less undesired side effect. After the absolute configuration of epothilone A (I) and B (2) were published by Höfle, et al, the total synthesis of epothilone and its derivate was intensively conducted. The first total synthesis of epothilone was published by Danishefsky et al, shortly followed by independent routes from Nicolou, et al. and Shinzer et al. Even though each group has own strategie, the three groups used olefin-methatesis,, macrolactonisation, and aldol reaction as coupling reactions.

Key words: Epothilone, totalsynthesis, olefin-Metatesis, macrolactonisation, aldol reaction