CAS Key Laboratory of Synthetic Chemistry of Natural Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032, China.
Chemistry. 2013 Feb 11;19(7):2539-47. doi: 10.1002/chem.201203467. Epub 2013 Jan 4.
The concise collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol has been accomplished in 10-15 steps, with the total synthesis of orientalol E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1) the intramolecular Heck reaction to access the azulene core, 2) the epoxidation-S(N)2' reduction sequence to access the allylic alcohol, 3) the efficient regioselective and stereoselective formal hydration of the bridging C=C bond in the synthesis of englerins, and 4) the late-stage chemo- and stereoselective C-H oxidation in the synthesis of orientalol E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalol E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).
已通过 10-15 步反应完成了对 englerin A 和 B、orientaol E 和 F 以及 oxyphyllol 的简洁总合成，这也是首次实现 orientaol E 和 oxyphyllol 的全合成。该成果得益于 9 和 10 的[4+3]环加成反应的实现。该合成的其他特点包括：1）实现了分子内 Heck 反应以获得薁核，2）采用环氧化-S（N）2'还原序列获得烯丙醇，3）在 englerin 的合成中高效实现桥接 C=C 键的区域选择性和立体选择性形式水合，以及 4）在 orientaol E 的合成中晚期的化学和立体选择性 C-H 氧化。这些天然产物的全合成使 oxyphyllol 的结构得到修正，并确定了有机催化[4+3]环加成反应的绝对立体化学特征。鉴定出 5 为天然产物 oxyphyllol，成功将 5 转化为 orientaol E，并且 englerin 和 oxyphyllol 均从同属 Phyllanthus 的植物中分离出来，这为我们提出的生物合成途径提供了支持。这项工作可能会使这些天然产物及其类似物和衍生物，特别是它们在对抗肾细胞癌（RCC）方面的潜力得到详细的生物评估。
