Kummer, David A.Li, DerunDion, AmelieMyers, Andrew2017-07-182011Kummer, David A., Derun Li, Amelie Dion, and Andrew G. Myers. 2011. “A Practical, Convergent Route to the Key Precursor to the Tetracycline Antibiotics.” Chemical Science 2 (9): 1710. doi:10.1039/c1sc00303h.2041-6520http://nrs.harvard.edu/urn-3:HUL.InstRepos:33464192Here we describe a 5-step sequence to prepare the AB enone 1, the key precursor to fully synthetic tetracyclines, that begins with a diastereoselective Michael–Claisen coupling of two simple starting materials, a cyclohexenone (compound 2 or, in a refinement, a substituted variant, vide infra) and the isoxazole ester 3. This advance defines an 8-step linear sequence to 6-deoxytetracycline antibiotics from three components of similar complexity (cyclohexenone 2, isoxazole ester 3, and structurally diverse D-ring precursors) in which sequential diastereoselective Michael–Claisen cyclization reactions form the A- and C-rings, respectively, of the linearly fused ABCD tetracycline skeleton. In addition to providing a readily scalable, practical route to fully synthetic tetracyclines of broad structural diversity, the sequence reported comprises a series of non-obvious stereoselective transformations, including a novel means for C12a hydroxylation.en-USJournal Article2017-05-1220112017-07-1810.1039/C1SC00303H