A practical, convergent route to the key precursor to the tetracycline antibiotics.
A practical, convergent route to the key precursor to the tetracycline antibiotics.
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DOI：
10.1039/c1sc00303h
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发表时间：
2011-09
期刊：
影响因子：
8.4
通讯作者：
Myers AG
中科院分区：
文献类型：
--
作者：
Kummer DA;Li D;Dion A;Myers AG
Here 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.
