Total syntheses of colchicine in comparison: a journey through 50 years of synthetic organic chemistry.
Colchicine, the major alkaloid of the meadow saffron, is one of the most prominent natural products and, like other tubulin-binding natural products (e.g. taxol and the epothilones), exhibits great pharmaceutical potential. The first syntheses in the late 1950s were milestones in natural product synthesis. But even today this structurally supposedly simple molecule poses a challenge to synthetic chemists. Only in the last years have syntheses been developed that are efficient enough to provide novel structurally modified colchicine analogues. The comparative examination of all known colchicine total syntheses undertaken in this Review not only reveals the tremendous progress in synthetic organic methodology over the past decades, but also shows how the unique synthetic problems posed by this molecule can be solved in an exceptionally creative manner. Only a few target molecules have been synthesized in such multifaceted ways.
Graening
Timm
T
Institut für Organische Chemie, Universität zu Köln, Greinstrasse 4, 50939 Köln, Germany.
Schmalz
Hans-Günther
HG
D002625:Chemistry, Organic / Q000379:methods; D003078:Colchicine / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry
D014404:Tubulin; D003078:Colchicine