Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2493-7. doi: 10.1002/anie.201511116. Epub 2016 Jan 14.
Ryanodane diterpenoids structurally share an extremely complex fused ring system, but differ in the substitution patterns of the hydroxy groups. Since these congeners exhibit various biologically important functions, their efficient chemical constructions have been greatly anticipated. We previously accomplished the total synthesis of ryanodine (1) using pentacycle 8 as the advanced intermediate. Here, we report the unified total syntheses of four distinct diterpenoids, 3-epi-ryanodol (3), cinnzeylanol (4), cinncassiols B (5), and A (6), from 8, all within 10 steps. A series of highly optimized chemo- and stereoselective reactions and protecting-group manipulations enabled assembly of the densely oxygenated structures of 3-6. Furthermore, the present synthetic studies established the C13S stereochemisty of 5-7 and revised the proposed structures of natural ryanodol (2) and cinnacasol (7) to be those of 3 and 6, respectively.
瑞诺丹二萜类化合物在结构上具有极其复杂的稠合环系统，但羟基的取代模式不同。由于这些同系物表现出各种具有重要生物学功能的特性，因此人们非常期待对其进行高效的化学构建。我们之前使用五环 8 作为高级中间体完成了瑞诺定（1）的全合成。在这里，我们报道了从 8 出发统一全合成了四种不同的二萜类化合物，3-表-瑞诺醇（3）、肉桂醇（4）、肉桂卡西醇 B（5）和 A（6），总共 10 步。一系列高度优化的化学和立体选择性反应以及保护基操作使得能够组装 3-6 的高度含氧结构。此外，本合成研究确定了 5-7 的 C13S 立体化学，并修正了天然瑞诺醇（2）和肉桂卡唑（7）的提议结构，分别为 3 和 6。
