天然产物曼宋酮E和F的合成工艺改进

Synthetic process improvement for natural products mansonone E and F

目的改进天然产物曼宋酮E和F的合成工艺。方法以2,5-二甲基萘醌为原料,经过8步反应得到曼宋酮F,经过9步反应得到曼宋酮E。其中,在二酯的选择性水解反应步骤、关环策略以及最后氧化为邻醌的氧化剂选择方面做了有效的改进。结果与结论产物经结构确证为曼宋酮E和F。曼宋酮F最后连续5步反应收率可达49%。改进后的合成路线提高了收率,降低了成本,多步反应可连续进行,减少了中间产物分离纯化环节。

An improved synthetic route was designed based on the method reported by Nunes et al. With 2,5- dimethyl naphthoquinone as the starting material, mansonone F and E were obtained after 8 and 9 steps reactions respectively. The important improvements include selective hydrolysis of ester group at position 4 with t-BuNH2, the use of tetrahydropyranyl group instead of benzyl group as protecting group for 4-phenolic hydroxyl group, and the use of PPA instead of dangerous expensive anhydrous borofluoric acid-ether solution as cyclization reagent to avoid benzyl migration by-product with increased yield of cyclization reaction. 2-10- doxybenzoic acid（IBX） was used as the oxidant instead of toxic selenium dioxide to give quantitative yield of mansonone F in the final oxidizing reaction. The structures of the target compounds were identified to be correct by using 1H-NMR, 13 C-NMR and HRMS. The overall yield of the last five steps for the synthesis of mansonone F was up to 49%. This improved synthetic route has significant value for large-scale preparation of mansonone E and F because of its high yield and efficiency with low cost.