Total synthesis of (-)-cylindrocyclophane A via a double Horner-Emmons macrocyclic dimerization event
Total synthesis of (-)-cylindrocyclophane A via a double Horner-Emmons macrocyclic dimerization event
复制标题
DOI：
10.1021/ja000429q
复制
发表时间：
2000-05-24
影响因子：
15
通讯作者：
Moon, B
中科院分区：
文献类型：
--
作者：
Hoye, TR;Humpal, PE;Moon, B
双氢环芳烷AF（1）是由摩尔及其同事从蓝色绿色植物地衣型双氢环芳烷（ATTC 29204）中分离得到的天然存在的细胞毒性[7.7]-对环芳烷。1 cylindrocyclophanes，沿着与相关的nostocyclophanes AD，是唯一已知的天然[7，7]-paracyclophanes。[2]最近，史密斯及其同事首次合成了这个家族的一个成员，圆柱环蕃F（1F）。3本文报道了柱环蕃A（1A）的合成，它在苄基C（1）和C（14）位上含有两个立体异构的和潜在反应活性的甲醇中心。我们设想通过双官能单体2的头-尾二聚化来构建C2对称大环核（方案1）。通过两个AZ单元的同时偶联4得到4的大环二聚本质上比2的差异保护形式的逐步偶联和随后的3的大环化在介入脱保护之后更有效。3，4，5合成分四步进行（方案2），从已知的醇（5）6到外消旋烯丙醇9。动力学拆分（Amano P-30脂肪酶，乙酸乙烯酯，己烷）得到（R）-乙酸酯10 [99.4%ee（手性HPLC）]。7回收的（S）-醇9 S可再氧化为烯酮8并循环使用。由光学纯的（R）-乙酸酯10（KHMDS，-78 ℃; TBSCl）8衍生的甲硅烷基烯酮缩醛在室温下顺利地进行[3，3]-σ迁移重排，得到TBS酯11.这种重新排列的容易性可能起源于较低的
Cylindrocyclophanes AF (1) are naturally occurring, cytotoxic [7.7]-paracyclophanes isolated by Moore and co-workers from the blue green alga, Cylindrospermum licheniforme Kützing (ATTC 29204). 1 The cylindrocyclophanes, along with the related nostocyclophanes AD, are the only known natural [7, 7]-paracyclophanes. 2 The first synthesis of a member of this family, cylindrocyclophane F (1F), was recently described by Smith and co-workers. 3 Here we report the synthesis of cylindrocyclophane A (1A), which includes two stereogenic and potentially reactive carbinol centers at the benzylic C (1) and C (14) positions. We envisioned the construction of the C2 symmetric macrocyclic core via head-to-tail dimerization of a bifunctional monomer 2 (Scheme 1). Macrocyclic dimerization by concurrent coupling4 of both AZ units to give 4 is inherently more efficient than stepwise coupling of differentially protected versions of 2 and subsequent macrocyclization of 3 following intervening deprotection. 3, 4, 5The synthesis proceeds in four steps (Scheme 2) from the known alcohol (5) 6 to the racemic allylic alcohol 9. Kinetic resolution (Amano P-30 lipase, vinyl acetate, hexane) gave (R)-acetate 10 [99.4% ee (chiral HPLC)]. 7 The recovered (S)-alcohol 9S could be reoxidized to enone 8 and recycled. The silylketene acetal derived from optically pure (R)-acetate 10 (KHMDS,-78 C; TBSCl) 8 smoothly underwent [3, 3]-sigmatropic rearrangement at room temperature to give TBS ester 11. The ease of this rearrangement might originate with the lower