Asymmetric crotylation reactions in synthesis of polypropionate-derived macrolides: Application to total synthesis of oleandolide
Asymmetric crotylation reactions in synthesis of polypropionate-derived macrolides: Application to total synthesis of oleandolide
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DOI：
10.1021/ja020853m
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发表时间：
2002-10-30
影响因子：
15
通讯作者：
Panek, JS
中科院分区：
文献类型：
--
作者：
Hu, T;Takenaka, N;Panek, JS
描述了大环内酯类抗生素齐墩果苷的苷元齐墩果酯(1)的收敛不对称合成的完整细节。合成是通过分别组装和偶联左侧和右侧亚基12和38来实现的。这些亚基是通过基于手性硅烷的不对称克隆化反应制备的，以控制立体化学关系。通过Pd(0)催化的SP(3)-SP(2)在锌中间体40和三氟乙烯基团38之间的交叉偶联反应，将左侧和右侧的亚基(C1-C7和C8-C14)连接在一起，得到27。该产品在山口条件下转化为Seco酸42a，再环合成内酯35。然后用间氯苯甲酸(m-CPBA)环氧化该原料，将正确的C8环氧化物安装成单一的非对映异构体，经过一段短的脱保护序列后，完成了齐墩果酯的合成。
Complete details of a convergent asymmetric synthesis of oleandolide (1), the aglycon of the macrolide antibiotic oleandomycin, is described. The synthesis has been achieved through the assembly and coupling of the left- and right-hand subunits 12 and 38, respectively. These subunits were prepared from chiral silane-based asymmetric crotylation reactions to control the stereochemical relationships. The left- and right-hand subunits (C1-C7 and C8-C14) were brought together through a Pd(0)-catalyzed sp(3)-sp(2) cross-coupling reaction between the zinc intermediate 40 and vinyl triflate 38 to give 27. This product was converted to seco acid 42a and cyclized to lactone 35 under Yamaguchi conditions. This material was then epoxidized with m-chloroperbenzoic acid (m-CPBA) to install the correct C8 epoxide as a single diastereomer, which after a short deprotection sequence completed the synthesis of oleandolide.