title: The Total Synthesis of Epothilone D as a Yardstick for Probing New Methodologies.
abstract: Here, a concise and highly convergent synthesis of epothilone D was investigated, relying on fragments of equal complexity that could be prepared in gram scale quantities. The strategy to construct the fragments includes the use of a previously reported enantiospecific zinc-catalyzed cross-coupling of an α-hydroxy ester triflate with a Grignard reagent, the application of a hydroboration/boron-magnesium exchange sequence for the rapid construction of the Z-substituted trisubstituted double bond present in the natural product, and a Noyori-type hydrogenation to install the β-hydroxy ester moiety of the southern part. The key to success is the diastereoselective head-to-tail macrolactonization by an intramolecular addition of the corresponding ω-alkynyl-substituted carboxylic acids to construct a new stereocenter in the macrocyclic core structure in one single step.
authors: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg im Breisgau, Germany.
authors: Alexander M
authors: AM
authors: Haydl
authors: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg im Breisgau, Germany.
authors: Bernhard
authors: 0000-0002-2514-3898
authors: B
authors: Breit
mesh_terms: D001895:Boron / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D034261:Epothilones; D007783:Lactones; D008274:Magnesium; D015032:Zinc; D001895:Boron; C114026:desoxyepothilone B
keywords: alkynes; macrocycles; natural products; rhodium; total synthesis