CONVERGENT TOTAL SYNTHESIS OF VINEOMYCINONE-B2 METHYL-ESTER AND ITS C(12)-EPIMER
CONVERGENT TOTAL SYNTHESIS OF VINEOMYCINONE-B2 METHYL-ESTER AND ITS C(12)-EPIMER
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DOI：
10.1021/ja00018a041
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发表时间：
1991-08-28
影响因子：
15
通讯作者：
SUZUKI, K
中科院分区：
文献类型：
--
作者：
MATSUMOTO, T;KATSUKI, M;SUZUKI, K
完成了醋酸霉素酮B2甲酯(7)及其C(12)-外聚体（epi-7）的全合成。构建芳基c -糖苷键的关键反应是O -> c -糖苷重排，从d -氟化油酰衍生物11和人醇衍生物21开始，提供了目标芳基c -糖苷区和立体控制的形成。Cp2HfCl2-AgClO4的组合作为该反应的特别有效的促进剂。对侧链的附加进行了广泛的模型研究。Lochmann-Schlosser碱对蒽衍生物19和20的邻位金属化有明显的影响。金属化产物可以被捕获为锡基衍生物，通过在甲苯中使用n-BuLi或优选MeLi生成相应的芳基锂。这些特定的反应条件是抑制RLi试剂在蒽的C(9)/C(10)-位置上的异常反应所必需的。通过将蒽衍生物25金属化，再与手性醛(S)-29反应，有效地实现了侧链部分的偶联。手性醛由对映体纯酸(S)-37通过酶动力学拆分得到。对苯基醇进行脱氧，然后进行几个步骤，总共合成了7个。从(R)-醛29开始，同样的反应顺序完成了epi-7的全合成。epi系列中间体为合成7的立体化学均匀性提供了有力的证据。
Total syntheses of vineomycinone B2 methyl ester (7) and its C(12)-epimer (epi-7) have been completed. The key reaction for construction of the aryl C-glycoside linkage is the O --> C-glycoside rearrangement starting from D-olivosyl fluoride derivative 11 and anthrol derivative 21, which provides the regio- and stereocontrolled formation of the aryl C-glycoside sector of the target. The combination of Cp2HfCl2-AgClO4 serves as a particularly efficient promoter for this reaction. An extensive model study for attaching the side chain is presented. The Lochmann-Schlosser base cleanly effects ortho metalation of anthracene derivatives 19 and 20. The metalated species can be trapped as stannyl derivatives, from which the corresponding aryllithium species are generated by using n-BuLi or preferably MeLi in toluene. These specific reaction conditions are necessary to suppress the abnormal reaction of RLi reagents at the C(9)/C(10)-positions of the anthracenes. Coupling of the side chain moiety was efficiently carried out by such metalation of anthracene derivative 25 followed by reaction with chiral aldehyde (S)-29. The chiral aldehyde was derived from enantiomerically pure acid (S)-37 obtained by enzymatic kinetic resolution. Deoxygenation of the benzylic alcohol function followed by several steps allowed the total ynthesis of 7. Starting from (R)-aldehyde 29, the same sequence of reactions accomplished the total synthesis of epi-7. The epi series of intermediates provided firm evidence for the stereochemical homogeneity of synthetic 7.