Evolution of the Total Synthesis of (-)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation, a Petasis-Ferrier Union/Rearrangement, and Ring-Closing Metathesis
Evolution of the Total Synthesis of (-)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation, a Petasis-Ferrier Union/Rearrangement, and Ring-Closing Metathesis
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DOI：
10.1021/ja8084669
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发表时间：
2009-02-18
影响因子：
15
通讯作者：
Basu, Kallol
中科院分区：
文献类型：
--
作者：
Smith, Amos B., III;Bosanac, Todd;Basu, Kallol
利用一种收敛策略，实现了抗肿瘤抗生素(-)-奥克拉霉素(1)的有效、不对称全合成以及绝对构型的指定。合成的亮点包括安装C(1)和C(13)立体中心的非对映选择性氧代重排/氧化序列，构建13元大环内嵌的高度功能化的四氢吡喃酮的Petsis-Ferrier联盟/重排，首次使用空间要求高的缩醛，分子内化学选择性酰化得到嵌入的双环内酯，以及有效的闭环复分解(RCM)反应生成大环环。
An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring.